OA12022A - Quinolyl propyl piperidine derivatives and their use as antibacterials. - Google Patents

Quinolyl propyl piperidine derivatives and their use as antibacterials. Download PDF

Info

Publication number
OA12022A
OA12022A OA1200200074A OA1200200074A OA12022A OA 12022 A OA12022 A OA 12022A OA 1200200074 A OA1200200074 A OA 1200200074A OA 1200200074 A OA1200200074 A OA 1200200074A OA 12022 A OA12022 A OA 12022A
Authority
OA
OAPI
Prior art keywords
propyl
acid
piperidine
methoxyquinolin
hydroxy
Prior art date
Application number
OA1200200074A
Other languages
French (fr)
Inventor
Jean-Luc Malleron
Michel Tabart
Jean-Christophe Carry
Michel Evers
Youssef Elahmad
Serge Mignani
Fabrice Vivani
Michel Cheve
Original Assignee
Aventis Pharma Sa
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Aventis Pharma Sa filed Critical Aventis Pharma Sa
Publication of OA12022A publication Critical patent/OA12022A/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Abstract

1-Substituted 4-(3-(6-alkoxy-4-quinolinyl)-propyl)-piperidine derivatives (I) are new. Quinolinylpropyl-piperidine derivatives of formula (I), in the form of diastereomers or their mixtures, and their salts are new. [Image] R 1H, halo or OH; R' 1H; or may also be halo if R 1= halo; R 0H; or R 0+ R 1bond, in which case R' 1= H; R 2COOH, CH 2COOH, CH 2CH 2COOH or CH 2OH; R 3(i) 1-6C alkyl substituted by 1-3 groups selected from OH, halo, oxo, COOH, alkoxycarbonyl, alkoxy, alkylthio, Ph', SPh' or Ph'-alkylthio, cycloalkyl, cycloalkylthio, Het and -S-Het; (ii) propargyl substituted by Ph', cycloalkyl or Het; (iii) cinnamyl or (iv) 4-phenylbuten-3-yl; provided that if R 3CH 2OH, then R 3= (i) 1-6C alkyl substituted by SPh', cycloalkylthio or -S-Het; or (ii) propargyl substituted by Ph', cycloalkyl or Het; R 41-6C alkyl, (2-6C) alkenyl-CH 2O- or (2-6C) alkynyl-CH 2O-; Ph' : phenyl (optionally substituted by 1-3 of halo, OH, alkyl, alkoxy, CF 3, OCF 3, COOH, alkoxycarbonyl, CN or NH 2); Het : 5- or 6-membered aromatic heterocycle containing 1-4 of N, O and S as heteroatom(s) (optionally substituted by 1-3 of halo, OH, alkyl, alkoxy, CF 3, OCF 3, oxo, COOH, alkoxycarbonyl, CN or NH 2); unless specified otherwise alkyl moieties have 1-3C and cycloalkyl moieties 3-7C. An independent claim is included for the preparation for (I). ACTIVITY : Antibacterial. (I) are effective in vitro against methicillin-resistant Staphylococcus aureusAS5155 at 0.03-4 Microg/ml, Streptococcus pneumoniaeIP53146 at 0.12-8 Microg/ml, Enterococcus faeciumat 0.5-64 Microg/ml and Moxarella catharrhalisIPA152 at 0.25-32 Microg/ml; and in vivo against Staphylococcus aureusIP8203 in mice at 10-150 mg/kg s.c. (CD 50) or (in some cases) 20-150 mg/kg p.o. (No specific results for individual compounds are given). MECHANISM OF ACTION : None given.

Description

120 2 2 1120 2 2 1

La présente invention concerne des dérivés de quinolyl propyl pipéridine de formulegénérale :The present invention relates to quinolylpropylpiperidine derivatives of the general formula:

qui sont actifs comme antimicrobiens. L’invention concerne également leur préparationet les compositions les contenant.which are active as antimicrobials. The invention also relates to their preparation and the compositions containing them.

Dans la demande de brevet WO 99/37635 ont été décrits des dérivés de quinolylpropyl pipéridine antimicrobiens, de formule générale :In patent application WO 99/37635 have been described antimicrobial quinolylpropyl piperidine derivatives, of general formula:

dans laquelle le radical Ri est notamment alcoxy (Cl-6), R? est hydrogène, R3 est enposition -2 ou -3 et représente alcoyle (Cl-6) pouvant être éventuellement substituépar 1 à 3 substituants choisis parmi thiol, halogène, alcoylthio, trifluorométhyl,alcoyloxycarbonyle, alcoylcarbonyle, alcènyloxycarbonyle, alcènylcarbonyle, hydroxy 15 éventuellement substitué par alcoyle ..., R4 est un groupe -CH2-R5 pour lequel R5 estsélectionné parmi alcoyle hydroxyalcoyle, alcènyle, alcynyle, tétrahydroluryle,phénylalcoyle éventuellement substitué, phénylalcényle éventuellement substitué,hétéroarylalcoyle éventuellement substitué, hétéroaroyle éventuellement substitué ..., nest 0 à 2, m est 1 ou 2 et A et B sont notamment oxygène, soufre, sulfinyle, sulfonyle, 20 CRéR? pour lequel Re et R-? représentent H, thiol, alcoylthio, halo, trifluorométhyle,alcènyle, alcènylcarbonyle, hydroxy, amino ... 1202Î ’in which the radical R 1 is in particular alkoxy (Cl-6), R? is hydrogen, R3 is -2 or -3 and represents alkyl (C1-6) which may be optionally substituted with 1 to 3 substituents selected from thiol, halogen, alkylthio, trifluoromethyl, alkyloxycarbonyl, alkylcarbonyl, alkenyloxycarbonyl, alkenylcarbonyl, hydroxy optionally substituted with alkyl, R4 is -CH2-R5 wherein R5 is selected from hydroxyalkyl, alkenyl, alkynyl, tetrahydroluryl, optionally substituted phenylalkyl, optionally substituted phenylalkenyl, optionally substituted heteroarylalkyl, optionally substituted heteroaroyl ..., n is 0-2 m is 1 or 2 and A and B are especially oxygen, sulfur, sulphinyl, sulphonyl, CReR? for which Re and R-? are H, thiol, alkylthio, halo, trifluoromethyl, alkenyl, alkenylcarbonyl, hydroxy, amino ... 1202

Dans la demande de brevet européen EP30044 ont été décrits des dérivés dequinoléine utiles comme cardiovasculaires, répondant à la formule générale :In the European patent application EP30044 have been described quinoline derivatives useful as cardiovascular, corresponding to the general formula:

A-B-CH2A-B-CH2

dans laquelle Ri est notamment alcoyloxy, A-B est -CH2-CH2-, -CHOH-CH?-,-CH2-CHOH-, -CH2-CO- ou -CO-CH?-, Ri est H, OH ou alcoyloxy, R2 est éthyle ouvinyle, R3 est notamment alcoyle, hydroxyalcoyle, cycloalcoyle, hydroxy, alcènyle,alcynyle, tétrahydrofùryle, phénylalcoyle, diphénylalcoyle éventuellement substitué,phénylalcényle éventuellement substitué, benzoyl ou benzoylalcoyle éventuellementsubstitué, hétéroaryle ou hétéroarylalcoyle éventuellement substitué et Z est H oualcoyle ou forme avec R3 un radical cycloalcoyle.wherein R 1 is especially alkyloxy, AB is -CH 2 -CH 2 -, -CHOH-CH 2 -, -CH 2 -CHOH-, -CH 2 -CO- or -CO-CH 2 -, R 1 is H, OH or alkyloxy, R 2 is ethyl-vinyl, R3 is especially alkyl, hydroxyalkyl, cycloalkyl, hydroxy, alkenyl, alkynyl, tetrahydrofuran, phenylalkyl, optionally substituted diphenylalkyl, optionally substituted phenylalkenyl, optionally substituted benzoyl or benzoylalkyl, optionally substituted heteroaryl or heteroarylalkyl and Z is Halkyl or forms with R3 a cycloalkyl radical.

Il a maintenant été trouvé, et c’est ce qui fait l’objet de la présente invention, que lesproduits de formule générale (I) pour lesquels :It has now been found, and this is the subject of the present invention, that the products of general formula (I) for which:

Ri est un atome d’hydrogène ou d’halogène, ou un radical hydroxy, R’i est un atome d’hydrogène, ou peut représenter halogène lorsque Ri est également un atome d’halogène, et R° est un atome d’hydrogène, ou bienR 1 is a hydrogen or halogen atom, or a hydroxy radical, R 1 is a hydrogen atom, or may represent halogen when R 1 is also a halogen atom, and R 0 is a hydrogen atom , or

Ri et R° forment ensemble une liaison et R’i est un atome d’hydrogène, R2 représente un radical carboxy, carboxyméthyle ou carboxy-2 éthyle, et R3 représente un radical alcoyle (1 à 6 atomes de carbone) substitué par 1 à 3substituants choisis parmi hydroxy, halogène, oxo. carboxy, alcoyloxycarbonylealcoyloxy, alcoylthio ou parmi un radical phényle, phénylthio ou phénylalcoylthiopouvant eux-même porter 1 à 4 substituants [choisis parmi halogène, hydroxy, alcoyle,alcoyloxy, trifluorométhyle, trifluorométhoxy, carboxy, alcoyloxycarbonyle, cyano,acétamido (1 à 4C) ou amino] ou parmi un radical cycloalcoyle ou cycloalcoylthio dont la partie cyclique contient 3 à 7 chaînons, ou parmi un radical hétérocvclyle ouhétérocyclylthio aromatique de 5 à 6 chaînons comprenant 1 à 4 hétéroatonqes choisisparmi l’azote, l’oxygène ou le soufre et éventuellement eux-même substitués [par 120 2 2 halogène, hydroxy, alcoyle, alcoyloxy, trifluorométhyle, trifluorométhoxy, oxo,carboxy, alcoyloxycarbonyle, cyano ou amino), ou R3 représente un radical propargylesubstitué par un radical phényle pouvant lui même porter 1 à 4 substituants [choisisparmi halogène, hydroxy, alcoyle, alcoyloxy, trifluorométhyle, trifluorométhoxy,carboxy, alcoyloxycarbonyle, cyano ou amino], ou substitué par un radicalcycloalcoyle contenant 3 à 7 chantons ou substitué par un radical hétérocyclylearomatique de 5 à 6 chaînons comprenant 1 à 4 hétéroatomes choisis parmi l’azote,l’oxygène ou le soufre et éventuellement lui-même substitué [par halogène, hydroxy,alcoyle, alcoyloxy, trifluorométhyle, trifluorométhoxy, oxo, carboxy,alcoyloxycarbonyle, cyano ou amino], ou Rj représente cinnamyle ou 4-phénylbutèn-3-yle, ou bien R2 représente un radical hydroxyméthyle, alcoyloxycarbonyle, alcoyloxycarbonyl-méthyle ou aIcoyIoxycarbonyl-2-éthyle (dont les portions alcoyle contiennent 1 à 6atomes de carbone) et R3 représente un radical alcoyle (1 à 6 atomes de carbone) substitué par un radicalphénylthio pouvant lui même porter 1 à 4 substituants [choisis parmi halogène,hydroxy, alcoyle, alcoyloxy, trifluorométhyle, trifluorométhoxy, carboxy,alcoyloxycarbonyle, cyano ou amino], par un radical cycloalcoylthio dont la partiecyclique contient 3 à 7 chaînons, ou par un radical hétérocyclylthio aromatique de 5 à6 chaînons comprenant 1 à 4 hétéroatomes choisis parmi l’azote, l’oxygène ou lesoufre et éventuellement lui même substitué [par halogène, hydroxy, alcoyle,alcoyloxy, trifluorométhyle, trifluorométhoxy, oxo, carboxy, alcoyloxycarbonyle,cyano ou amino] ou R3 représente un radical propargyle substitué par un radicalphényle pouvant lui même porter 1 à 4 substituants [choisis panni halogène, hydroxy,alcoyle, alcoyloxy, trifluorométhyle, trifluorométhoxy, carboxy, alcoyloxycarbonyle,cyano ou amino], ou substitué par un radical cycloalcoyle contenant 3 à 7 chaînons ousubstitué par un radical hétérocyclyle aromatique de 5 à 6 chaînons comprenant 1 à 4hétéroatomes choisis parmi l’azote, l’oxygène ou le soufre et éventuellement lui-mêmesubstitué [par halogène, hydroxy, alcoyle, alcoyloxy, trifluorométhyle,trifluorométhoxy, oxo, carboxy, alcoyloxycarbonyle, cyano ou amino], et R4 représente un radical alcoyle (contenant 1 à 6 atomes de carbone), alcényl-Chl·-ou alcynyl-CH2- dont les parties alcényle ou aîcynyle contiennent 2 à 6 atomes decarbone, étant entendu que les radicaux et portions alcoyle sont en en chaîne droite ou ramifiée, 420 2 2 sous leurs formes diastéréoisomères ou leurs mélanges, ainsi que leurs sels, sont depuissants agents antibactériens.R 1 and R 6 together form a bond and R 1 is a hydrogen atom, R 2 represents a carboxy, carboxymethyl or 2-carboxyethyl radical, and R 3 represents an alkyl radical (1 to 6 carbon atoms) substituted with 1 to 3substituents selected from hydroxy, halogen, oxo. carboxy, alkyloxycarbonylalkyloxy, alkylthio or from a phenyl, phenylthio or phenylalkylthiopower radical themselves carry 1 to 4 substituents [selected from halogen, hydroxy, alkyl, alkyloxy, trifluoromethyl, trifluoromethoxy, carboxy, alkyloxycarbonyl, cyano, acetamido (1 to 4C) or amino] or from a cycloalkyl or cycloalkylthio radical in which the cyclic portion contains 3 to 7 members, or from a 5- to 6-membered aromatic heterocyclic or heterocyclylthio radical having 1 to 4 heteroatoms selected from nitrogen, oxygen or sulfur and optionally -substituted by halogen, hydroxy, alkyl, alkyloxy, trifluoromethyl, trifluoromethoxy, oxo, carboxy, alkyloxycarbonyl, cyano or amino), or R3 represents a propargyl radical substituted by a phenyl radical which can itself carry 1 to 4 substituents [ selected from halogen, hydroxy, alkyl, alkyloxy, trifluoromethyl, trifluoromethoxy, carboxy, alkyloxy arbonyl, cyano or amino], or substituted with a 3- to 7-membered cycloalkyl radical or substituted with a 5- to 6-membered heterocyclylearomatic radical comprising 1 to 4 heteroatoms selected from nitrogen, oxygen or sulfur and optionally itself substituted [by halogen, hydroxy, alkyl, alkyloxy, trifluoromethyl, trifluoromethoxy, oxo, carboxy, alkyloxycarbonyl, cyano or amino], or R 1 represents cinnamyl or 4-phenylbuten-3-yl, or R2 represents a hydroxymethyl, alkyloxycarbonyl or alkyloxycarbonyl radical; -methyl or alkyloxycarbonyl-2-ethyl (whose alkyl portions contain 1 to 6 carbon atoms) and R3 represents an alkyl radical (1 to 6 carbon atoms) substituted by a phenylthio radical which can itself carry 1 to 4 substituents [selected from halogen , hydroxy, alkyl, alkyloxy, trifluoromethyl, trifluoromethoxy, carboxy, alkyloxycarbonyl, cyano or amino], by a cycloalkylthio radical whose The polyalkyl group contains 3 to 7 members, or a 5- to 6-membered aromatic heterocyclylthio radical containing 1 to 4 heteroatoms selected from nitrogen, oxygen or sulfur and optionally itself substituted [by halogen, hydroxy, alkyl, alkyloxy, trifluoromethyl, trifluoromethoxy, oxo, carboxy, alkyloxycarbonyl, cyano or amino] or R3 represents a propargyl radical substituted with a phenyl radical which can itself carry 1 to 4 substituents [selected from halogen, hydroxy, alkyl, alkyloxy, trifluoromethyl, trifluoromethoxy, carboxy, alkyloxycarbonyl, cyano or amino], or substituted with a 3- to 7-membered cycloalkyl radical or substituted with a 5- to 6-membered aromatic heterocyclyl radical having 1 to 4 heteroatoms selected from nitrogen, oxygen or sulfur and optionally itself substituted by halogen , hydroxy, alkyl, alkyloxy, trifluoromethyl, trifluoromethoxy, oxo, carboxy, alkyloxycarbonyl, cyano or amino], and R4 represents an alkyl radical (containing 1 to 6 carbon atoms), alkenyl-Ch1- or alkynyl-CH2- whose alkenyl or alkynyl parts contain 2 to 6 carbon atoms, it being understood that the radicals and portions Alkyl are straight or branched chain, in their diastereoisomeric forms or mixtures thereof, and their salts, are dexterous antibacterial agents.

Il est entendu que les radicaux et portions alcoyle sont en chaîne droite ou ramifiée etcontiennent (sauf mention spéciale) 1 à 4 atomes de carbone, et que dans l’alternativeoù Ri ou R’i repésentent un atome d’halogène ou lorsque R3 porte un substituanthalogène, celui-ci peut être choisi parmi fluor, chlore, brome ou iode. De préférence lefluor.It is understood that the radicals and alkyl portions are in a straight or branched chain and contain (unless otherwise stated) 1 to 4 carbon atoms, and that in the alternative where R 1 or R 1 represent a halogen atom or when R 3 bears a Halogen substituent, it can be selected from fluorine, chlorine, bromine or iodine. Preferably lefluor.

Dans la formule générale ci-dessus, lorsque R3 porte un substituant hétérocyclylearomatique, ce dernier peut être choisi (à titre non limitatif) parmi thiényle, iuryle,pyrrolyle, imidazolyle, thiazolyle, oxazolyle, thiadiazolyle, oxadiazolyle, tétrazolyle,pyridyle, pyridazinyle, pyrazinyle, pyrimidinyle. Il est également entendu que dans ladéfinition de R3 le radical alcoyle substitué ne porte simultanément qu’un seul radicalcyclique.In the above general formula, when R 3 bears a heterocyclylearomatic substituent, the latter may be chosen (but not limited to) from thienyl, iuryl, pyrrolyl, imidazolyl, thiazolyl, oxazolyl, thiadiazolyl, oxadiazolyl, tetrazolyl, pyridyl, pyridazinyl and pyrazinyl. , pyrimidinyl. It is also understood that in the definition of R3 the substituted alkyl radical simultaneously carries only one cyclic radical.

Selon l’invention, les produits de formule générale (I) peuvent être obtenus parcondensation de la chaîne R3 sur le dérivé de quinolyl propyl pipéridine de formulegénérale :According to the invention, the products of general formula (I) can be obtained by equilibration of the R3 chain on the quinolylpropylpiperidine derivative of general formula:

dans laquelle R4 est défini comme précédemment, R", et R"’i représentent des atomesd’hydrogène ou forment ensemble un radical oxo et R\ représente un radical carboxy,carboxyméthyle ou carboxy-2 éthyle protégés, ou un radical alcoyloxycarbonyle,alcoyloxycarbonylméthyle ou alcoyloxycarbonyl-2-éthyle, pour obtenir un dérivé dequinolyl propyl pipéridine de formule générale :in which R 4 is defined as above, R ", and R" 'i represent hydrogen atoms or together form an oxo radical and R 1 represents a protected carboxy, carboxymethyl or 2-carboxy-ethyl radical, or an alkyloxycarbonyl, alkyloxycarbonylmethyl or alkyloxycarbonyl-2-ethyl, to obtain a quinolylpropylpiperidine derivative of general formula:

(III) 120 2 ? pour lequel R"i, R"’i, R’? et R4 sont définis comme ci-dessus et R3 est défini commeprécédemment, suivie le cas échéant de l'élimination du radical protecteur d'acide, puis le cas échéant suivie de la réduction du radical oxo représenté par R"i et R"’i enun alcool pour lequel Ri représente hydroxy puis éventuellement de l’halogénation sil’on veut obtenir un dérivé de quinolyl propyl pipéridine pour lequel Ri est un atomed’halogène, et éventuellement de la déhydrohalogénation du dérivé halogénécorrespondant, pour obtenir un dérivé de quinolyl propyl pipéridine pour lequel Ri etR° forment ensemble une liaison, ou bien de la dihalogénation du produit de formulegénérale (III) pour lequel R"i et R"’i forment ensemble un radical oxo pour obtenir undérivé de quinolyl propyl pipéridine pour lequel Ri et R’i sont des atomes d’halogène, et/ou le cas échéant suivie de la réduction de l’acide protégé sous forme d’un radicalR\ en position -3 de la pipéridine, en un radical hydroxyméthyle et éventuellement dela transformation en un radical carboxyméthyle ou carboxy-z éthyle selon les méthodeshabituelles, puis éventuellement suivie de l’élimination du radical protecteur d’acide etéventuellement de la transformation du produit obtenu en un sel.(III) 120 2? for which R "i, R" 'i, R'? and R4 are defined as above and R3 is defined as above, optionally followed by removal of the acid-protecting group, followed, if necessary, by reduction of the oxo radical represented by R "i and R". an alcohol for which R 1 represents hydroxy and optionally halogenation if it is desired to obtain a quinolylpropylpiperidine derivative for which R 1 is an atom of halogen, and optionally dehydrohalogenation of the corresponding halogen derivative, to obtain a quinolylpropylpiperidine derivative; for which R 1 and R 8 together form a bond, or of the dihalogenation of the product of general formula (III) for which R "i and R" 'i together form an oxo radical to obtain a quinolylpropylpiperidine derivative for which R 1 and R' i are halogen atoms, and / or where appropriate followed by the reduction of the protected acid as a radical R \ at the -3 position of the piperidine, in a hydroxymethyl radical and optionally of the conversion to a carboxymethyl or carboxy-ethyl radical according to the usual methods, then optionally followed by removal of the acid-protecting radical and possibly the conversion of the product obtained into a salt.

La condensation de la chaîne R3 sur la pipéridine s’effectue avantageusement paraction d’un dérivé de formule générale :The condensation of the R 3 chain with piperidine is advantageously carried out by the action of a derivative of general formula:

RrX (IV) dans laquelle R3 est défini comme précédemment et X représente un atomed’halogène, un radical méthylsulfonyle, un radical trifluorométhylsulfonyle oup.toluènesulfonyle, en opérant en milieu anhydre, de préférence inerte (azote ou argonpar exemple) dans un solvant organique tel qu’un amide (diméthylformamide parexemple), une cétone (acétone par exemple) ou un nitriîe (acétonitrile par exemple) enprésence d’une base telle qu’une base organique azotée (par exemple triéthylamine) ouune base minérale (carbonate alcalin : carbonate de potassium par exemple) à unetempérature comprise entre 20°C et la température de reflux du solvant.R 1 X (IV) in which R 3 is defined as above and X represents an atom of halogen, a methylsulfonyl radical, a trifluoromethylsulphonyl or p-toluenesulphonyl radical, operating in an anhydrous medium, preferably inert (nitrogen or argon for example) in an organic solvent such as an amide (dimethylformamide, for example), a ketone (for example acetone) or a nitrite (acetonitrile for example) in the presence of a base such as a nitrogenous organic base (for example triethylamine) or a mineral base (alkaline carbonate: carbonate of potassium for example) at a temperature between 20 ° C and the reflux temperature of the solvent.

De préférence, on fait agir un dérivé pour lequel X est un atome de brome ou d’iode. 120 2 2Preferably, a derivative is used for which X is a bromine or iodine atom. 120 2 2

Lorsque R3 représente propargyle substitué par phényle, cycloalcoyle ou hétérocyclyle,il est souvent préférable de condenser un halogénure de propargyle, puis de substituerla chaîne par un radical phényle, cycloalcoyle ou hétérocyclyle.When R 3 is propargyl substituted with phenyl, cycloalkyl or heterocyclyl, it is often preferable to condense a propargyl halide and then substitute the chain with a phenyl, cycloalkyl or heterocyclyl radical.

Dans cette alternative, l’addition de la chaîne propargylique s’effectue au moyen debromure de propargyle, dans les conditions énoncées ci-dessus pour R3 en présence ounon d’un iodure de métal alcalin comme par exemple l’iodure de potassium ou desodium.In this alternative, the addition of the propargyl chain is carried out by means of propargyl bromide, under the conditions set forth above for R 3 in the presence or absence of an alkali metal iodide, for example potassium iodide or sodium iodide.

Lorsqu’il s’agit de la substitution par un radical phényle ou hétérocyclyle, la réactions’effectue par action d’un halogénure dérivé du radical cyclique à substituer, enprésence de triéthylamine, en milieu anhydre dans un solvant tel qu’un amide(diméthylformamide par exemple) ou un nitrile (acétonitrile par exemple) et enprésence d’un sel de palladium comme par exemple le tétrakis triphénylphosphinepalladium et d’iodure cuivreux, à une température comprise entre 20°C et latempérature de reflux du solvant.In the case of substitution with a phenyl or heterocyclyl radical, the reaction is carried out by the action of a halide derived from the cyclic radical to be substituted, in the presence of triethylamine, in an anhydrous medium in a solvent such as an amide (dimethylformamide). for example) or a nitrile (acetonitrile for example) and in the presence of a palladium salt such as tetrakis triphenylphosphinepalladium and cuprous iodide, at a temperature between 20 ° C and the reflux temperature of the solvent.

Lorsqu’il s’agit de la substution par un groupement cycloaikyle, la réaction s’effectuepar action d’un organolithien comme le n.butyllithium ou le tert-buiyllithium sur ledérivé propargylique obtenu précédemment, en milieu anhydre dans un éther commepar exemple le tétrahydrofurane à une température comprise entre -78 et 0°C, puisaction d’une cycloalcanone suivi de la désoxygénation de l’alcool intermédiaire selonles méthodes classiques.When it comes to the substitution with a cycloalkyl group, the reaction is carried out by the action of an organolithium such as n-butyllithium or tert-buiyllithium on the propargylic acid obtained above, in an anhydrous medium in an ether, for example tetrahydrofuran at a temperature between -78 and 0 ° C, thenaction of a cycloalkanone followed by deoxygenation of the intermediate alcohol according to conventional methods.

Il est entendu que, lorsque les radicaux alcoyle représentés par R3 portent dessubstituants carboxy ou amino, ces derniers sont préalablement protégés, puis libérésaprès la réaction. On opère selon les méthodes habituelles qui n’altèrent pas le reste dela molécule, notamment selon les méthodes décrites par T.W. Greene et P.G.M. Wuts,Protective Groups in Organic Synthesis (2eme éd.), A. Wiley - Interscience Publication(1991), ou par Mc Omie, Protective Groups in Organic Chemistry, Plénum Press(1973).It is understood that when the alkyl radicals represented by R 3 bear carboxyl or amino substituents, the latter are protected beforehand and then released after the reaction. The procedure is carried out according to the usual methods which do not affect the remainder of the molecule, in particular according to the methods described by T.W. Greene and P.G.M. Wuts, Protective Groups in Organic Synthesis (2nd ed.), A. Wiley - Interscience Publication (1991), or by Mc Omie, Protective Groups in Organic Chemistry, Plenum Press (1973).

Le radical carboxy protégé représenté par R’2 peut être choisi parmi les estersfacilement hydrolysables. A titre d’exemple peuvent être cités les esters méthylique,benzylique, tertiobutylique, ou bien les esters de phénylpropyle ou de propargyle.Eventuellement la protection du radical carboxy s’effectue simultanément à la réaction.Dans ce cas le produit de formule' générale (II) mis en oeuvre porte un radicalR’: = carboxy. 120 22The protected carboxy radical represented by R'2 may be chosen from easily hydrolysable esters. By way of example, mention may be made of methyl, benzyl or tert-butyl esters or of phenylpropyl or propargyl esters. Optionally, the protection of the carboxy radical is carried out simultaneously with the reaction. In this case, the product of general formula ( II) has a radical R '= carboxy. 120 22

La réduction du radical oxo en un alcool s’effectue selon les méthodes habituelles quin’altèrent pas le reste de la molécule, notamment par action d’un agent réducteurcomme par exemple un hydrure (borohydrure alcalin : borohydrure de sodium ou depotassium, triacétoxy-borohydrure de sodium, cyanoborohydrure de sodium parexemple, hydrure d’aluminium et de lithium ou hydrure de diisobutyl aluminium) enopérant de préférence dans sous atmosphère inerte, dans un solvant organique commeun alcool (méthanol, éthanol, isopropanol par exemple), ou un éther (par exempletétrahydrofuranne) ou un solvant chloré (par exemple dichorométhane) à unetempérature comprise entre 20°C et la température de reflux du solvant. L’halogénation destinée à obtenir un dérivé de quinolyl propyl quinoléine pour lequelR’i est un atome d’halogène, à partir du dérivé pour lequel R’i est hydroxy, peut êtremise en oeuvre en présence d’un trifluorure d’aminosouffe (trifluorure de diéthylaminosoufre, trifluorure de bis(2-méthoxyéthyl)amino soufre (Deoxofluor® ), trifluorure demorpholino soufre par exemple) ou alternativement en présence de tétrafluorure desoufre, au moyen d’un réactif comme un halogénure de tétra alkylammonium, detri alkyl benzylammonium ou de tri alkyl phénylammonium ou au moyen d’unhalogénure de métal alcalin additionné éventuellement d’un éther couronne. Laréaction de fluoration peut être également mise en oeuvre par action d’un agent defluoration comme un fluorure de soufre [par exemple trifluorure de morpholino soufre,tétrafluorure de soufre (J. Org. Chem., 40. 3808 (1975)), trifluorure de diéthylaminosoufre (Tetrahedron, 44, 2875 (1988)), trifluorure de bis(2-méthoxyéthyl)amino soufre(Deoxofluor®). Alternativement la réaction de fluoration peut aussi s’effectuer aumoyen d’un agent de fluoration comme lhexafluoropropyl diéthylamine (JP 2 039 546)ou la N-(chloro-2 trifluoro-1,1,2 éthyl) diéthylamine.The reduction of the oxo radical to an alcohol is carried out according to the usual methods which do not alter the rest of the molecule, in particular by the action of a reducing agent such as for example a hydride (alkaline borohydride: sodium borohydride or potassium, triacetoxy-borohydride sodium hydroxide, for example sodium cyanoborohydride, aluminum hydride and lithium hydride or diisobutyl aluminum hydride) preferably operating under an inert atmosphere, in an organic solvent such as an alcohol (methanol, ethanol, isopropanol for example), or an ether (for example exempletetrahydrofuran) or a chlorinated solvent (eg dichloromethane) at a temperature of between 20 ° C and the reflux temperature of the solvent. The halogenation intended to obtain a quinolylpropylquinoline derivative for which R'i is a halogen atom, from the derivative for which R'i is hydroxy, may be carried out in the presence of an aminosulfide trifluoride (trifluoride) of diethylaminosulfur, bis (2-methoxyethyl) amino sulfur trifluoride (Deoxofluor®), sulfur trifluoride, for example) or alternatively in the presence of unsaturated tetrafluoride, using a reagent such as a tetraalkylammonium halide, alkyl benzylammonium trifluoride or tri alkyl phenylammonium or with an alkali metal halide optionally supplemented with a crown ether. The fluorination reaction can also be carried out by the action of a defluorination agent such as sulfur fluoride [for example sulfur morpholino trifluoride, sulfur tetrafluoride (J. Org. Chem., 40, 3808 (1975)), trifluoride of diethylaminosulfur (Tetrahedron, 44, 2875 (1988)), bis (2-methoxyethyl) amino sulfur trifluoride (Deoxofluor®). Alternatively the fluorination reaction can also be carried out by means of a fluorinating agent such as hexafluoropropyl diethylamine (JP 2,039,546) or N- (2-chloro-1,1,2-trifluoroethyl) diethylamine.

Lorsque l’on met en oeuvre un halogénure de tétra alkylammonium, ce dernier peutêtre choisi, à titre d’exemple, parmi les halogénures de tétra méthylammonium, detétra éthylammonium, de tétra propylammonium, de tétra butylammonium (tétra n-butylammonium par exemple), de tétra pentylammonium, de tétra cyclohexyl-ammonium, de tri éthyl méthylammonium de tri butyl méthylammonium, ou detri méthyl propylammonium.When a tetraalkylammonium halide is used, the latter may be chosen, for example, from tetra methylammonium, tetraethylammonium, tetrapropylammonium or tetra-butylammonium halides (tetra-n-butylammonium, for example), tetra pentylammonium, tetra cyclohexylammonium, triethyl methylammonium triethylammonium triethyl, or methyl propylammonium triri.

On opère dans un solvant organique tel qu’un solvant chloré (par exempledichlorométhane, dichloréthane, chloroforme) ou dans un éther (tétrahydrofurane,dioxanne par exemple) à une température comprise entre -78 et 40°C (de préférenceentre 0 et 30°C). Il est avantageux d’opérer en milieu inerte (argon ou azotenotamment). 120 2 2The reaction is carried out in an organic solvent such as a chlorinated solvent (for example dichloromethane, dichloroethane, chloroform) or in an ether (tetrahydrofuran, dioxane, for example) at a temperature of between -78 and 40 ° C. (preferably between 0 and 30 ° C. ). It is advantageous to operate in an inert medium (argon or azotenotamment). 120 2 2

Il est également possible d’opérer par traitement par un agent d’halogénation commele chlorure de thionyle ou trichlorure de phosphore dans un solvant organique telqu’un solvant chloré (dichlorométhane, chloroforme par exemple), à une températurecomprise entre 0°C et la température de reflux du mélange réactionnel.It is also possible to work by treatment with a halogenating agent such as thionyl chloride or phosphorus trichloride in an organic solvent such as a chlorinated solvent (dichloromethane, chloroform for example) at a temperature between 0 ° C and the temperature reflux of the reaction mixture.

La dihalogénation du produit de formule générale (III) pour lequel R"i et R"’i formentensemble un radical oxo pour obtenir un dérivé de quinolyl propyl pipéridine pourlequel Ri et R’i sont des atomes d’halogène peut être mise en oeuvre dans desconditions analogues à celles de l’halogénation ci-dessus.The dihalogenation of the product of general formula (III) for which R "i and R" 'i form together an oxo radical to obtain a quinolylpropylpiperidine derivative for which Ri and R'i are halogen atoms can be used in conditions similar to those of halogenation above.

La déhydrohalogénation du dérivé halogéné obtenu à partir du dérivé pour lequel Riest hydroxy peut être mise en oeuvre notamment par traitement par lediazabicyclo[5,4,0]undéc-7-ène dans un solvant organique aromatique (toluène parexemple), à une température comprise entre 20°C et la température de reflux dumélange réactionnel.The dehydrohalogenation of the halogenated derivative obtained from the derivative for which Ri is hydroxy may be carried out in particular by treatment with lediazabicyclo [5.4.0] undec-7-ene in an aromatic organic solvent (toluene for example), at a temperature of between 20 ° C and the reflux temperature of the reaction mixture.

La réduction de l’acide protégé sous forme d’un radical RS en position -3 de lapipéridine, en un radical hydroxyméthyle s’effectue selon les méthodes habituelles quin’altèrent pas le reste de la molécule, notamment on opère par action d’un hydrure(hydrure d’aluminium et de lithium ou hydrure de diisobutyl aluminium par exemple)dans un solvant tel qu’un éther (tétrahydrofurane par exemple) à une températurecomprise entre 20 et 60°C.The reduction of the protected acid in the form of a radical RS in the position -3 of lapiperidine, in a hydroxymethyl radical is carried out according to the usual methods that do not alter the rest of the molecule, in particular one operates by action of a hydride (lithium aluminum hydride or diisobutyl aluminum hydride for example) in a solvent such as an ether (tetrahydrofuran for example) at a temperature between 20 and 60 ° C.

La transformation du radical hydroxyméthyle en position -3 de la pipéridine en unradical carboxyméthyle s’effectue selon les méthodes habituelles qui n’altèrent pas lereste de la molécule, notamment elle peut être mise en oeuvre par action d’un agentd’halogénation comme par exemple le chlorure de thionyle ou le trichlorure dephosphore ou le tribromure de phosphore puis d'un cyanure alcalin (cyanure depotassium ou cyanure de sodium par exemple) pour préparer le dérivé cyanométhylecorrespondant, suivie de l’hydrolyse du nitrile. L’halogénation peut être effectuée dans un solvant chloré (dichlorométhane,chloroforme par exemple), à une température comprise entre 0°C et la température dereflux du solvant.The conversion of the hydroxymethyl radical to the 3-position of the piperidine to unradical carboxymethyl is carried out according to the usual methods which do not alter the ester of the molecule, in particular it can be carried out by the action of a halogenating agent such as, for example thionyl chloride or phosphorus trichloride or phosphorus tribromide and then an alkaline cyanide (potassium cyanide or sodium cyanide for example) to prepare the corresponding cyanomethyl derivative, followed by hydrolysis of the nitrile. The halogenation can be carried out in a chlorinated solvent (dichloromethane, chloroform for example) at a temperature between 0 ° C. and the reflux temperature of the solvent.

La réaction du cyanure alcalin peut être mise en oeuvre dans un solvant comme lediméthylsulfoxyde, un amide (diméthylformamide par exemple), une cétone (acétonepar exemple), un éther comme par exemple le tétrahydrofurane ou un alcool comme 12 0 2 2 par exemple le méthanoi ou l’éthanol, à une température comprise entre 20°C et latempérature de reflux du mélange réactionnel. L’hydrolyse du nitrile s'effectue selon les méthodes classiques qui n’altèrent pas lereste de la molécule, notamment par action de l’acide chlorhydrique en milieuméthanolique, à une température comprise entre 20 et 70°C, suivi de la saponificationde l’ester obtenu (par exemple par l’hydroxyde de sodium dans un mélange de dioxaneet d’eau), ou bien directement par action de l’acide sulfurique aqueux à unetempérature comprise entre 50 et 80°C.The reaction of the alkaline cyanide can be carried out in a solvent such as dimethylsulfoxide, an amide (dimethylformamide for example), a ketone (acetone for example), an ether such as tetrahydrofuran or an alcohol such as methanol. or ethanol, at a temperature between 20 ° C and the reflux temperature of the reaction mixture. The hydrolysis of the nitrile is carried out according to conventional methods which do not alter the ester of the molecule, in particular by the action of hydrochloric acid in methanol medium, at a temperature between 20 and 70 ° C., followed by the saponification of the ester obtained (for example by sodium hydroxide in a mixture of dioxane and water), or directly by the action of aqueous sulfuric acid at a temperature between 50 and 80 ° C.

La transformation du radical hydroxyméthyle en position -3 de la pipéridine en unradical carboxy-2 éthyle s’effectue par exemple à partir du dérivé halogéné, préparécomme décrit ci-dessus, par condensation du sel de sodium du malonate de diéthylesuivie de l’hydrolyse acide en milieu aqueux du produit obtenu. L’élimination le cas échéant du radical protecteur d’acide pour obtenir un dérivé dequinolyl propyl pipéridine pour lequel R2 est un radical carboxy, s’effectue selon lesméthodes habituelles, notamment par hydrolyse acide ou saponification de l’ester R’2.Notamment on fait agir la soude en milieu hydroorganique, par exemple dans un alcoolcomme le méthanoi ou un éther comme le dioxanne, à une température comprise entre20°C et la température de reflux du mélange réactionnel. On peut également mettre enoeuvre l’hydrolyse en milieu chlorhydrique aqueux à une température comprise entre20 et 100°C.The conversion of the hydroxymethyl radical to the 3-position of the piperidine to unradical 2-carboxyethyl is carried out, for example, from the halogenated derivative, prepared as described above, by condensation of the sodium salt of diethyl malonate with acid hydrolysis. in an aqueous medium of the product obtained. The elimination, if appropriate, of the acid-protecting radical to obtain a quinolylpropylpiperidine derivative for which R2 is a carboxy radical is carried out according to the usual methods, in particular by acid hydrolysis or saponification of the R'2 ester. causes the sodium hydroxide to react in a hydroorganic medium, for example in an alcohol such as methanol or an ether such as dioxane, at a temperature of between 20 ° C. and the reflux temperature of the reaction mixture. Hydrolysis can also be carried out in an aqueous hydrochloric medium at a temperature of between 20 and 100 ° C.

Le dérivé de quinolyl propyl pipéridine de formule générale (II) ou l’acidecorrespondant pour lequel R’2 représente un radical carboxy, peut être préparé selonou par analogie avec les méthodes décrites ci-après dans les exemples ou selon ou paranalogie avec les méthodes décrites dans la demande de brevet européen EP 30044 oudans la demande internationale WO 99/37635. Les intermédiaires des dérivés dequinolyl propyl pipéridine pour lesquels R4 représente alcényl-CH?O- oualcynyl-CH2O- peuvent être obtenus par analogie avec la préparation desintermédiaires pour lesquels R4 est alcoyloxy, par action du dérivé halogénécorrespondant sur le dérivé de quinoléine hydroxylé en position -6.The quinolylpropylpiperidine derivative of general formula (II) or the corresponding acid for which R'.sub.2 represents a carboxy radical may be prepared according to or in analogy with the methods described hereinafter in the examples or according to or paranalogy with the described methods. in the European patent application EP 30044 or in the international application WO 99/37635. The intermediates of the quinolylpropylpiperidine derivatives for which R4 represents alkenyl-CH2O-alkynyl-CH2O- can be obtained by analogy with the preparation of the intermediates for which R4 is alkyloxy, by the action of the corresponding halogen derivative on the hydroxylated quinoline derivative in the position - 6.

Le dérivé carboxy-2 éthyle protégé de formule générale (II) peut être obtenu selon oupar analogie avec la méthode décrite dans la demande internationale WO 99/37635suivie de l’hydrolyse du nitrile et de l’esterification de l’acide ainsi obtenu, ou peut êtrepréparé selon ou par analogie avec les méthodes décrites ci-après dans les exemples. 120 2 2 10The 2-carboxy-protected ethyl derivative of general formula (II) may be obtained according to orat analogy with the method described in international application WO 99/37635Follow-up of the hydrolysis of nitrile and the esterification of the acid thus obtained, or can be prepared according to or by analogy with the methods described hereinafter in the examples. 120 2 2 10

Il est entendu que les dérivés de formule générale (I), (II), (ΙΠ), ou leurs intermédiaires de départ peuvent exister sous forme cis ou trans au niveau des substituants en position -3 et -4 de la pipéridine. Les dérivés de configuration trans peuvent être obtenus à partir des dérivés de configuration cis selon ou par analogie avec la méthode 5 décrite dans la demande internationale WO 99/37635.It is understood that the derivatives of general formula (I), (II), (ΙΠ), or their starting intermediates may exist in cis or trans form at the substituents at position -3 and -4 of the piperidine. Trans configuration derivatives can be obtained from cis configuration derivatives according to or analogy with the method described in international application WO 99/37635.

Les dérivés de quinolyl propyl pipéridine de formule générale (I) peuvent être purifiésle cas échéant par des méthodes physiques telles que la cristallisation ou lachromatographie.The quinolylpropylpiperidine derivatives of general formula (I) can be purified, if appropriate, by physical methods such as crystallization or chromatography.

Par ailleurs il est entendu que lorsque R’i est un atome d’hydrogène et R| est hydroxyio ou halogène, il existe des formes diastéréoisomères et que les formesdiastéréoisomères et leurs mélanges entrent aussi dans le cadre de la présenteinvention. Ces derniers peuvent être notamment séparés par chromatographie sur silice ou par Chromatographie Liquide Haute Performance (CLHP).Moreover, it is understood that when R'i is a hydrogen atom and R | is hydroxy or halogen, there are diastereoisomeric forms and diastereoisomeric forms and mixtures thereof are also within the scope of the present invention. These can be separated in particular by chromatography on silica or by high performance liquid chromatography (HPLC).

Les dérivés de quinolyl propyl pipéridine de formule générale (I) peuvent être 15 transformés en sels d’addition avec les acides, par les méthodes connues. Il est entenduque ces sels entrent aussi dans le cadre de la présente invention.The quinolylpropylpiperidine derivatives of general formula (I) can be converted to acid addition salts by known methods. It is understood that these salts are also within the scope of the present invention.

Comme exemples de sels d'addition avec des acides pharmaceutiquement acceptables,peuvent être cités les sels formés avec les acides minéraux (chlorhydrates,bromhydrates, sulfates, nitrates, phosphates) ou avec les acides organiques (succinates, 20 fumarates, tartrates, acétates, propionates, maléates, citrates, méthanesulfonates,éthanesulfonates, phénylsulfonates, p.toluènesulfonates, iséthionates, naphtylsulfonatesou camphorsulfonates, ou avec des dérivés de substitution de ces composés).As examples of addition salts with pharmaceutically acceptable acids, mention may be made of the salts formed with the mineral acids (hydrochlorides, hydrobromides, sulphates, nitrates, phosphates) or with the organic acids (succinates, fumarates, tartrates, acetates, propionates). , maleates, citrates, methanesulphonates, ethanesulphonates, phenylsulphonates, toluenesulphonates, isethionates, naphthylsulphonates or camphorsulphonates, or with substitution derivatives of these compounds).

Certains des dérivés de quinolyl propyl pipéridine de formule générale (I) portant unradical carboxy peuvent être transformés à l’état de sels métalliques ou en sels 25 d’addition avec les bases azotées selon les méthodes connues en soi. Ces sels entrentégalement dans le cadre de la présente invention. Les sels peuvent être obtenus paraction d'une base métallique (par exemple alcaline ou alcalino terreuse), de l'ammoniacx ou d'une amine, sur un produit selon l'invention, dans un solvant approprié tel qu'un 120 2 2 11 alcool, un éther ou l’eau, ou par réaction d'échange avec un sel d'un acide organique.Le sel formé précipite après concentration éventuelle de la solution, il est séparé parfiltration, décantation ou lyophilisation. Comme exemples de sels pharmaceutiquementacceptables peuvent être cités les sels avec les métaux alcalins (sodium, potassium,lithium) ou avec les métaux alcalinoterreux (magnésium, calcium), le sel d'ammonium,les sels de bases azotées (éthanolamine, diéthanolamine, triméthylamine, triéthylamine,méthylamine, propylamine, diisopropylamine, NN-diméthyléthanolamine, benzylamine,dicyclohexylamine, N-benzyl-P-phénéthylamine, NN'-dibenzyléthylènediamine,diphénylènediamine, benzhydrylamine, quinine, choline, arginine, lysine, leucine,dibenzylamine).Some of the quinolylpropylpiperidine derivatives of the general formula (I) bearing a carboxy radical may be converted to the form of metal salts or addition salts with the nitrogenous bases by the methods known per se. These salts are also within the scope of the present invention. The salts can be obtained by action of a metal base (for example alkaline or alkaline earth), ammonia or an amine, on a product according to the invention, in a suitable solvent such as a 120 2 2 11 alcohol, an ether or water, or by exchange reaction with a salt of an organic acid.The salt formed precipitates after optional concentration of the solution, it is separated by filtration, decantation or lyophilization. As examples of pharmaceutically acceptable salts may be mentioned salts with alkali metals (sodium, potassium, lithium) or with alkaline earth metals (magnesium, calcium), ammonium salt, nitrogen base salts (ethanolamine, diethanolamine, trimethylamine, triethylamine, methylamine, propylamine, diisopropylamine, N, N-dimethylethanolamine, benzylamine, dicyclohexylamine, N-benzyl-P-phenethylamine, N, N'-dibenzylethylenediamine, diphenylenediamine, benzhydrylamine, quinine, choline, arginine, lysine, leucine, dibenzylamine).

Les dérivés de quinolyl propyl pipéridine selon l’invention sont des agentsantibactériens particulièrement intéressants.The quinolylpropylpiperidine derivatives according to the invention are particularly interestingantibacterial agents.

In vitro, sur germes gram positifs les dérivés de quinolyl propyl pipéridine selonl’invention se sont montrés actifs à des concentrations comprises entre 0,015 et4 pg/ml sur Staphylococcus aureus AS5155 résistante à la méticilline, ainsi que lamajorité d'entre eux à des concentrations comprises entre 0,06 et 8 pg/ml surSîreptococcus pneumoniae IP53146 et à des concentrations comprises entre 0,12 et64 pg/ml sur Enterococcus faecium ATCC19434 ou H983401 et sur germes gramnégatifs, ils se sont montrés actifs à des concentrations comprises entre 0,12 et32 pg/ml sur Moraxella catharrhalis IPA152 ; in vivo, ils se sont montrés actifs surles infections expérimentales de la souris à Staphylococcus aureus IP8203 à des dosescomprises entre 10 et 150 mg/kg par voie sous cutanée (DC50) et pour certains d’entreeux à des doses comprises entre 20 et 150 mg/kg par voie orale.In vitro, on gram-positive seeds the quinolylpropylpiperidine derivatives according to the invention have been active at concentrations of between 0.015 and 4 μg / ml on meticillin-resistant Staphylococcus aureus AS5155, as well as the majority of them at concentrations included between 0.06 and 8 μg / ml on Streptococcus pneumoniae IP53146 and at concentrations between 0.12 and 64 μg / ml on Enterococcus faecium ATCC19434 or H983401 and on gram-negative organisms, they were active at concentrations between 0.12 and 32 μg / ml. pg / ml on Moraxella catharrhalis IPA152; in vivo, they were active in experimental infections of the mouse with Staphylococcus aureus IP8203 at doses of between 10 and 150 mg / kg subcutaneously (DC50) and for some of them at doses of between 20 and 150 mg / kg orally.

Enfin, les produits selon l’invention sont particulièrement intéressants du fait de leurfaible toxicité. Aucun des produits n’a manifesté de toxicité à la dose de 100 mg/kgpar voie sous cutanée chez la souris (2 administrations).Finally, the products according to the invention are particularly interesting because of their low toxicity. None of the products showed toxicity at the dose of 100 mg / kg subcutaneously in mice (2 administrations).

Parmi les produits selon l'invention, plus particulièrement intéressants sont les dérivésde quinolyl propyl quinoléine de formule générale (I) pour lesquels : 12 0 2 2 12Among the products according to the invention, more particularly of interest are the quinolylpropyl quinoline derivatives of general formula (I) for which: ## STR2 ##

Ri est un atome d’hydrogène ou d’halogène, ou un radical hydroxy, R’i est un atome d’hydrogène, et R° est un atome d’hydrogène, ou bienR 1 is a hydrogen or halogen atom, or a hydroxy radical, R 1 is a hydrogen atom, and R 0 is a hydrogen atom, or

Ri et R° forment ensemble une liaison et R’i est un atome d’hydrogène, R2 représente un radical carboxy ou carboxyméthyle, et R3 représente un radical alcoyle (1 à 6 atomes de carbone) substitué par 1 à 3substituants choisis parmi halogène, oxo, alcoyloxy, alcoylthio ou parmi un radicalphényle ou phénylthio pouvant eux-même porter 1 à 4 atomes d'halogène ou parmi unradical cycloalcoyle ou cycloalcoylthio dont la partie cyclique contient 3 à 7 chaînons,ou parmi un radical hétérocyclyle ou hétérocyclylthio aromatique de 5 à 6 chaînonscomprenant 1 à 4 hétéroatomes choisis parmi l’azote, l’oxygène ou le soufre etéventuellement eux-même substitués par halogène, ou R3 représente un radicalpropargyle substitué par un radical phényle pouvant lui même porter 1 à 3 substituantshalogène, ou propargyle substitué par un radical hétérocyclyle aromatique de 5 à 6chaînons comprenant 1 à 4 hétéroatomes choisis parmi l’azote, l’oxygène ou le soufre,ou R 3 représente cinnamyle, ou bien R2 représente un radical hydroxyméthyle, alcoyloxycarbonyle ou alcoyloxycarbonyl-méthyle (dont les portions alcoyle contiennent 1 à 6 atomes de carbone) etR3 représente un radical alcoyle (1 à 6 atomes de carbone) substitué par un radicalhétérocyclylthio aromatique de 5 à 6 chaînons comprenant 1 à 4 hétéroatomes choisisparmi l’azote, l'oxygène ou le soufre ou R3 représente un radical propargyle substituépar un radical hétérocyclyle aromatique de 5 à 6 chaînons comprenant 1 à 4hétéroatomes choisis parmi l’azote, l’oxygène ou le soufre, et R4 représente un radical alcoyle (contenant 1 à 6 atomes de carbone), les radicaux et portions alcoyle étant en en chaîne droite ou ramifiée, ainsi que lesformes diastéréoisomères ou leurs mélanges, ainsi que leurs sels. et parmi ces produits, plus spécialement préférés sont les produits suivants: • acide (3R,4R)-4-[3-hydroxy,-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2-thiényl-thio)éthyl]pipéridine-3-acétique, 120 2 2 13 • acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2-thiénylthio)éthyl] pipéridine-3-acétique ; • acide (3R,4R)-4-[3-fluoro-3-(6-méthoxyquinolin-4-yl)propylj-1 -[2-(2-thiényl-sulfanyl)éthyl]pipéridine-3-acétique ; • acide (3R,4R)-1 -[2-(3-fluorophénylthio)éthyl]-4-[3-hydroxy-3-(6-méthoxy- quinolin-4-yl)propylJpipéridine-3-acétique ; • acide (3R,4R)-4-[3-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,3,5-tri-fluorophényl)prop-2-ynyl]pipéridine-3-carboxylique.R 1 and R 6 together form a bond and R 1 is a hydrogen atom, R 2 represents a carboxy or carboxymethyl radical, and R 3 represents an alkyl radical (1 to 6 carbon atoms) substituted with 1 to 3 substituents selected from halogen, oxo, alkyloxy, alkylthio or from a phenyl or phenylthio radical which can themselves carry 1 to 4 halogen atoms or from a cycloalkyl or cycloalkylthio radical whose ring portion contains 3 to 7 ring members, or from an aromatic heterocyclyl or heterocyclylthio radical of 5 to 6-memberedcomprises 1 to 4 heteroatoms selected from nitrogen, oxygen or sulfur and optionally themselves substituted by halogen, or R3 represents a propargyl radical substituted with a phenyl radical which can itself carry 1 to 3 halogen substituents, or propargyl substituted with a 5 to 6-membered aromatic heterocyclyl radical comprising 1 to 4 heteroatoms selected from nitrogen, oxygen or sulfur e, or R 3 represents cinnamyl, or R2 represents a hydroxymethyl, alkyloxycarbonyl or alkyloxycarbonylmethyl radical (the alkyl portions of which contain 1 to 6 carbon atoms) and R3 represents an alkyl radical (1 to 6 carbon atoms) substituted with a aromatic 5- to 6-membered aromatic heterocyclylthio radical having 1 to 4 heteroatoms selected from nitrogen, oxygen or sulfur or R3 represents a propargyl radical substituted with a 5- to 6-membered aromatic heterocyclyl radical having 1 to 4 heteroatoms selected from nitrogen, oxygen or sulfur, and R4 represents an alkyl radical (containing 1 to 6 carbon atoms), the radicals and alkyl portions being in straight or branched chain, as well as diastereoisomeric forms or mixtures thereof, as well as their salts. and among these products, more particularly preferred are the following products: (3R, 4R) -4- [3-hydroxy, -3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2 thienylthio) ethyl] piperidine-3-acetic acid, (2R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2- thienylthio) ethyl] piperidine-3-acetic acid; (3R, 4R) -4- [3-fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienyl-sulfanyl) ethyl] piperidine-3-acetic acid; (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3-hydroxy-3- (6-methoxypinolin-4-yl) propyl] piperidine-3-acetic acid; (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl) ] piperidin-3-carboxylic acid.

Les produits cités dans les exemples sont particulièrement préférés ; les dérivés dequinolyl propyl pipéridine ci-après sont également des produits intéressants :The products cited in the examples are particularly preferred; the derivatives of quinolylpropylpiperidine below are also interesting products:

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-phénylbutyl]pipéridine-3-caiboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4-phenylbutyl] piperidine-3-caiboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4~(2-fluorophényl)butyl]pipéridine- 3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1 - [4 - (2-fluorophenyl) butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(3-fluorophényl)butyl]pipéridine- 3-caiboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (3-fluorophenyl) butyl] piperidine-3-caiboxylic acid

Acide (3R,4R)-4~[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-fluorophényl)propyl]pipéridine- 3-carboxylique(3R, 4R) -4 - [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(4-fluorophényl)butyl]pipéridine- 3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (4-fluorophenyl) butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,3-difluorophényl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(2,3-difluorophényl)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (2,3-difluorophenyl) butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,6-difluorophényl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propylj-1 -[4-(2,6-difluorophényl)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (2,6-difluorophenyl) butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-chlorophényl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenyl) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l -[4-(2-chlorophényl)butyl] pipéridine- 3-carboxylique 12 0 2 2 14(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (2-chlorophenyl) butyl] piperidine-3-carboxylic acid 12 0 2 2 14

Acide (3R,4R>4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-chlorophényl)propyl]pipéridine-3-carboxyIique(3R, 4R) 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenyl) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthox\quinolin-4-yl)propyl]-l-[4-(3-chlorophényI)butyl] pipéridine- 3-carboxylique(3R, 4R) -4- [3- (6-Methoxynolin-4-yl) propyl] -1- [4- (3-chlorophenyl) butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méihoxyqumolin-4-yl)propyl]-1 -[3-(4-chlorophényl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methyloxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenyl) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)^-[3-(6-méthoxyquinolin^}-yl)propyl]-1 -[4-(4-chlorophényl)butyl] pipéridine- 3-carboxylique(3R, 4R) 1- [3- (6-Methoxyquinolin-1-yl) propyl] -1- [4- (4-chlorophenyl) butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,3-dichlorophényl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichlorophenyl) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-inéthox}'qumolm-4-yl)propyl]-1 -[4-(2,3-dichlorophényl)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Inethoxy) qumolm-4-yl) propyl] -1- [4- (2,3-dichlorophenyl) butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,6-dichlorophényl)propyl]pipéridine-3-cafboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,6-dichlorophenyl) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)^-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(2,6-dichlorophényl)butyl]pipéridine-3-caiboxyiique(3R, 4R) - [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (2,6-dichlorophenyl) butyl] piperidine-3-caiboxylic acid

Acide (3R,4R)-^-[3-(6-méthoxyquinolin^-yl)propyl]-1 -[3-(2-méthylphényl)propyl]pipéridine-3-carboxylique(3R, 4R) -N - [3- (6-Methoxyquinolin-1-yl) propyl] -1- [3- (2-methylphenyl) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-mélhoxyquinolin-4-yl)propyl]-1 -[4-(2-méthylphényl)butyl]pipéridine- 3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (2-methylphenyl) butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[5-(2-mé±ylphényl)pentyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methyl-quinolin-4-yl) propyl] -1- [5- (2-methylphenyl) pentyl] piperidine-3-carboxylic acid

Acide (3R,4R)^4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthylphényl)propyl]pipéridine-3-carboxylique(3R, 4R) 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenyl) propyl] piperidine-3-carboxylic acid

Acide (3R-4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(3-méthylphényl)butyl]pipéridme- 3-carboxvlique(3R-4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (3-methylphenyl) butyl] piperidin-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(Améthvlphényl)propy]]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (Amethylphenyl) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(4-mé±ylphényl)butyl]pipéridine- 3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (4-methylphenyl) butyl] piperidine-3-carboxylic acid

Acide (3R.4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-méthoxyphénvl)propyl]pipéridine-3 -carboxylique(3-4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenyl) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolm^-yl)propyl]-1 -[4-(2-méthoxyphényl)'butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolyl-yl) propyl] -1- [4- (2-methoxyphenyl) butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propylj-1 -[3-(3-méthoxyphényl^)propyl]pipéridine-3-carboxylique 12022 15(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenyl) propyl] piperidine-3-carboxylic acid 12022

Acide (3R,4R)-4-[3-(6-méflioxyquinolin-4-yl)propyl]-l-[4-(3-inéüioxyphényl)buiyl] pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Meflioxyquinolin-4-yl) propyl] -1- [4- (3-iminooxyphenyl) bylyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méîhoxyquinolin-4-yl)propyl]-l-[3-(4-méthoxyphényl)propyl] pipéridine-3-caiboxylique 5 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(4-méthoxyphényl)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenyl) propyl] piperidine-3-caiboxylic Acid Acid (3R, 4R) -4 - [3- (6-methoxyquinolin-4-yl) propyl] -l- [4- (4-methoxyphenyl) butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-inéthoxyquinolin-4-yl)propyl]-1 -[3-(2-trifluorométhylphényl)propyl]pipéridine-3-carboxylique . Acide (3R,4R)-4-[3-(6-niéthoxyquinolin-4-yl)propyl]-l-[4-(2-trifluoromélhylphényl)butyl]10 pipéridine-3-caiboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethylphenyl) propyl] piperidine-3-carboxylic acid. (3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (2-trifluoromethylphenyl) butyl] piperidine-3-caiboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinoIin-4-yl)propyl]-l-[3-(3-trifluorométhylphényl)propyl]pipàidine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinin-4-yl) propyl] -1- [3- (3-trifluoromethylphenyl) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-mé!hoxyquinolin-4-yl)propyl]-l-[4-(3-Îrifluorométhylphényl)butyl]pipéridine-3-caiboxylique 15 Acide (3R,4R)-4-[3-(6-méthoxyqximolm-4-yl)propyl]-1 -[3-(4-trifluorométhylphényl)propyl] pipéridme-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (3-fluorrifluoromethylphenyl) butyl] piperidine-3-caiboxylic acid (3R, 4R) 4- [3- (6-Methoxyqximolm-4-yl) propyl] -1- [3- (4-trifluoromethylphenyl) propyl] piperidin-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-métbo?cyquinolin-4-yl)propyl]-1 -[4-(4-trifluorométhylphényi)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methylcyquinolin-4-yl) propyl] -1- [4- (4-trifluoromethylphenyl) butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-phénylthio-propyl]pipéridine-3-20 carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3-phenylthio-propyl] piperidine-3-20 carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2-fluorophénylthio)propyl]pipéridine-3-caiboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenylthio) propyl] piperidine-3-caiboxylic acid

Acide (3R,4R) 4-[3-(6“méthoxyqumoiin-4~yl)propyl]-l-[3-(3-fluorophéaiylthio)propyl]pipéridine-3-caiboxylique 2 5 Acide (3R,4R)-4“[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(4-fluorophénylthio)éthyl] pipéridine-3-carboxylique(3R, 4R) 4- [3- (6-Methoxy-4-yl) propyl] -1- [3- (3-fluorophenylthio) propyl] -piperidine-3-caiboxylic acid Acid (3R, 4R) -4 "[3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (4-fluorophenylthio) ethyl] piperidine-3-carboxylic acid"

Acide (3R,4R)-4-[3-(6-méthoxyqumolin-4-yl)propyl]-1 - [3-(4-fluorophénylthio)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquolin-4-yl) propyl] -1- [3- (4-fluorophenylthio) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2,3-difluorophényltbio)éthyl] 30 pipéridine-3-caiboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (2,3-difluorophenylthio) ethyl] piperidine-3-caiboxylic acid

Acide (3R,4R)-4-[3-(6-mélhoxyquinolin-4-yl)propyl]-1 -[3-(2,3-difluorophénylthio)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenylthio) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyi]-1 -[2-(2,6-difluorophénylthio)éthyl]pipéridine-3-carboxylique 3 5 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,6-difluorophénylthio)propyl] pipéridine-3-carboxylique 120 2 2 16(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (2,6-difluorophenylthio) ethyl] piperidine-3-carboxylic acid acid (3R, 4R) ) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenylthio) propyl] piperidine-3-carboxylic acid 120 2 2 16

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l -[2-(2-chlorqphénylthio)éthyl] pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (2-chloro-phenylthio) ethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-niéthoxyquinolin-4-yl)propyl]-1 -[3-(2-chlorophénylthio)propyl] pipéridine-3-cait>oxylique 5 Acide (3R,4R)-4-[3-(6-niéthoxyquinolin-4-yl)propyl]-l-[2-(3-chlorophénylîhio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenylthio) propyl] piperidine-3-acetylbasic acid acid (3R, 4R) -4- [3- (6-niéthoxyquinolin-4-yl) propyl] -l- [2- (3-chlorophénylîhio) ethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-(3-chlorophénylthio)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquolin-4-yl) propyl] -1- [3- (3-chlorophenylthio) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolm-4-yl)propyl]-1 -[2-(4-chlorophényl±io)éthyl] 10 pipéridine-3-cafboxylique(3R, 4R) -4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [2- (4-chlorophenyl) i) ethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(4-chlorophénylihio)propyl]pipéridine-3-cafboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenyl) i) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)^4-[3-(6-méthoxyquinolm-4-yl)propyl]-1 -[2-(2,3-dichlorophénylthio)éthyl]pipéridine-3-carboxylique 15 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]- l-[3-(2,3-dich!orophénylthio)propyl] pipéridine-3-caiboxylique(3R, 4R) 4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [2- (2,3-dichlorophenylthio) ethyl] piperidine-3-carboxylic acid acid (3R, 4R) 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichlorophenylthio) propyl] piperidine-3-caiboxylate

Acide (3R4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2,6-dichlorophényitbio)éthyl]pipéridine-3-cafboxylique(3R4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (2,6-dichlorophenylthio) ethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[3-(2,6-dichlorophénylthio)propyl] 2 o pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinin-4-yl) propyl] -1- [3- (2,6-dichlorophenylthio) propyl] -2-piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2-méthylphénylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (2-methylphenylthio) ethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-méthylphénylthio)propyl]pipéridine-3-caiboxylique 2 5 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3-méthylphénylthio)éthyl] pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenylthio) propyl] piperidine-3-caiboxylic acid Acid (3R, 4R) - 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (3-methylphenylthio) ethyl] piperidine-3-carboxylic acid

Acide (3R,4R)^t-[3-(6-méthoxyquinolin^-yl)propyl]-1 -[3-(3-méthylphénylthio)propyl]pipéridine-3-carboxylique(3R, 4R) 1- [3- (6-Methoxyquinolin-1-yl) propyl] -1- [3- (3-methylphenylthio) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]- l-[2-(4-méthylphénylthio)éthyl] 3 o pipéridme-3-carboxyiique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (4-methylphenylthio) ethyl] 3-piperidin-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-inéthoxyquinolin-4-yl)propyI]-1 -[3-(4-méthylphénylthio)propvl]pipéridine-3-carboxylique ' Acide (3R4R)-4-[3-(6-méthoxyquinohn-4-yl)propyl]-1 -[2-(2-tnfluorométhyIhénylthio)éthyl]* pipéridine-3-carboxylique 3 5 Acide (3R,4R)^4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2-triflurométhylphénylthio)x propyl]pipéridine-3-carboxylique 12 0 2 2 17(3R, 4R) -4- [3- (6-Inethoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenylthio) propyl] piperidine-3-carboxylic acid (3R4R) -4- 3- (6-Methoxyquinino-4-yl) propyl] -1- [2- (2-tnfluoromethyl) phenylthio) ethyl] piperidine-3-carboxylic acid (3R, 4R) 4- [3- (6-methoxyquinolin) 4-yl) propyl] -1- [3- (2-trifluromethylphenylthio) x propyl] piperidine-3-carboxylic acid 12 0 2 2 17

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4--yl)propyl]-l-[2-(3-trifluorométhylphénylthio) éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethylphenylthio) ethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(3-triflurométhylphénylthio) propyl]pipâidine-3-carboxyiique 5 Acide (3R,4R)-4-[3-(6-nié±oxyquinolin-4~yl)propyl]-l-[2-(4-trifluorométhylphénylthio)éthyi]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquolin-4-yl) propyl] -1- [3- (3-trifluromethylphenylthio) propyl] pipadidine-3-carboxylic acid acid (3R, 4R) -4 - [3- (6-denied ± oxyquinolin-4-yl) propyl] -l- [2- (4-trifluoromethylphenylthio) éthyi] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-] -[3-(4-triflurométhylphénylthio)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -] - [3- (4-trifluromethylphenylthio) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2-méthoxyphényltbio)éthyl]ίο pipéridine-3-caiboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (2-methoxyphenylbio) ethyl] ί-piperidine-3-caiboxylic acid

Acide (3R,4R)-4-[3-(6-niéthoxyquinolin-4-yl)propyI]-l-[3-(2-inéthoxyphénylihio)propyl]pipéridine-3-caiboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenyl) i) propyl] piperidine-3-caiboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyqumolm-4-yl)propyl]-1 -[2^3-méthoxyphényltbio)éthyl]pipéridine-3-cafboxylique 15 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyI]-l-[3-(3-méthoxyphénylthio)propyl]pipéridine-3-caiboxylique(3R, 4R) -4- [3- (6-Methoxyqumol-4-yl) propyl] -1- [2H-3-methoxyphenylthio] ethyl] piperidine-3-coffee carboxylic acid (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyI] -l- [3- (3-methoxyphenylthio) propyl] piperidin-3-caiboxylique

Acide (3Ri4R)-4-[3-(6-mé{hoxyquinolin-4-yl)propyl]-1 -[2-(4-méthoxyphénylthio)éthyI]pipéridine-3-carboxylique(3R14R) -4- [3- (6-Methyloxyquinolin-4-yl) propyl] -1- [2- (4-methoxyphenylthio) ethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l -[3-(4-méthoxyphénylthio)propyl]20 pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenylthio) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méîhoxyquinolin-4-yl)propyl]-1 -[cyclopropylméthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [cyclopropylmethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(cyclopropyî)étbyl]pipéridine-3carboxylique 2 5 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[cyclobutylméthyl]pipéridine-3- carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (cyclopropyl) ethyl] piperidin-3-carboxylic acid Acid (3R, 4R) -4- [3 (6-Methoxyquinolin-4-yl) propyl] -1- [cyclobutylmethyl] piperidine-3-carboxylic

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(cyclobutyl)éîhyî]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (cyclobutyl) hexyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3'(6-méthox\'quinolin-4-yl)propylj-1 -[cyclopentylméthyl]pipéridine-3- 3 o carboxylique(3R, 4R) -4- [3 '(6-Methoximinolin-4-yl) propyl] -1- [cyclopentylmethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(cyclopentyl)éthyl]pipéridine-3carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentyl) ethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[cyclohexylméthyl]pipéridine-3-carboxylique 3 5 Acide (3R,4R)-4-[3-(6-méthox>quinolin-4-yl)propyl]-1 -[2-(cyclohexyl)éthyl jpipéridine-3 · carboxylique 12 0 2 2 18(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1 - [cyclohexylmethyl] piperidine-3-carboxylic acid acid (3R, 4R) -4- [3- (6) methoxy-quinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl) -piperidine-3-carboxylic acid 12 0 2 2 18

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(cyclopropylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (cyclopropylthio) ethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)prqpyl]-l -[3-{cyclopropylthio)propyI]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (cyclopropylthio) propyl] piperidine-3-carboxylic acid

Acide (3R,4R>4-[3-(6-méthoxyqumolin-4-yl)propyl]-1 -[2-(cyclobutylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) 4- [3- (6-Methoxyquolin-4-yl) propyl] -1- [2- (cyclobutylthio) ethyl] piperidine-3-carboxylic acid

Acide (3R,4R>4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(cyclobutylthiopropyl]pipéridine- 3-carboxylique(3R, 4R) 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (cyclobutylthiopropyl) piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l -[2-(cyclopentylthio)éthyl]pipéridine- 3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-3-carboxylic acid

Acide (3R,4R>4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(cyclopentylthio)propyl]pipéridme- 3-carboxylique(3R, 4R) 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (cyclopentylthio) propyl] piperidin-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(cyclohexylthio)propyl]pipéridine- 3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (cyclohexylthio) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-méthylthioéü:yl]pipéridine-3-caiboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2-methylthio-1-yl] piperidine-3-caiboxylic acid

Acide (3R,4R)^-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-méthylthiopropyl]pipéridine-3-carboxylique(3R, 4R) - [3- (6-Methoxyquinolin-4-yl) propyl] -1 - [3-methylthiopropyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l -[2-é±ylthioéthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2-ethylthioethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-éthylthiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3-ethylthiopropyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-mé±oxyquinolin-4-yl)propyl]- 1 -[2-(n-propylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methyl-quinolin-4-yl) propyl] -1- [2- (n-propylthio) ethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(n-propylthio)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [3- (n-propylthio) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(n-butylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (n-butylthio) ethyl] piperidine-3-carboxylic acid

Acide (3R.4R)-4-[3-{6-méÎhoxyquinolin-4-yl)propyl]-1 -[3-(n-butylthio)propyl]pipéridine-3-carboxylique(3-4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (n-butylthio) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyqumolin-4-yl)propyl]-l-[4-(thien-2-yl)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquolin-4-yl) propyl] -1- [4- (thien-2-yl) butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolm^-yl)propyl]-1 -[3-(thien-2-yl)thiopropyl]pipéridine- 3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinol-1-yl) propyl] -1- [3- (thien-2-yl) thiopropyl] piperidine-3-carboxylic acid

Acide (3RAR)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(5-chloro-thien-2-yl)propyl]pipéridine-3-carboxylique 120 2 2 19(3RAR) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (5-chloro-thien-2-yl) propyl] piperidine-3-carboxylic acid 120 2 2 19

Acide (3R,4R)-4-[3-(6-màhoxyquinoîin-4-yl)propyl]-l-[4-(5-chloro-thien-2-yl)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinin-4-yl) propyl] -1- [4- (5-chloro-thien-2-yl) butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4'yl)propyl]-1 -[2-(5-chloro-thien-2-yl)thioéthyl]pipéridine-3-carboxylique 5 Acide (3R,4R)-4-[3-(6-méthoxyquinoiin-4-yl)propyl]-1 -[3-(5-cbloro-thien-2-yl)thiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4'-yl) propyl] -1- [2- (5-chloro-thien-2-yl) thioethyl] piperidine-3-carboxylic acid acid ( 3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chloro-thien-2-yl) thiopropyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinoiin-4-yi)propyI]-1 -[3-(3-chloro-tbien-2-yI)propyI3pipéridine-3-carboxylique . Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl3-l-[4-(3-chloro-thien-2-yl)butyl] 10 pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-tert-2-yl) propyl] piperidine-3-carboxylic acid. (3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (3-chloro-thien-2-yl) butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l -[2-(3-chloro-thien-2-yl)thioéthyl]pipéridine-3-cafboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (3-chloro-thien-2-yl) thioethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl3-l -[3-(3-chloro-thien-2-yl)thiopropyl]pipéridine-3-carboxylique 15 .Acide (3R,4R)-4-[3“(6-méthoxyquinolm-4-yl)propyl]-l-[3-(5-métiiyl -thien-2-yl)propyl]pipéridine-3-caiboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-thien-2-yl) thiopropyl] piperidine-3-carboxylic acid 15 .Acid ( 3R, 4R) -4- [3 "(6-methoxyquinol-4-yl) propyl] -1- [3- (5-methylthien-2-yl) propyl] piperidine-3-caiboxylic

Acide (3R,4R)-4-[3-(6-mélhoxyquinolin-4-yl)propyl3-l -[4-(5-méthyl -îhien-2-yl)butyl]pipéridine-3-caiboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (5-methyl-2-yl) butyl] piperidine-3-caiboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(5-méthyl -thien-2-yl)thioéthyl]20 pipéridine-3-carboxyEque(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (5-methylthth-2-yl) thioethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yi)propyl]-l-[3-(5-méthyl-thien-2*yl)thiopropyi]pipéiidine-3-caiboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (5-methyl-thien-2-yl) thiopropyl] piperidine-3-caiboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propylj- l-[3-(3-méthyl -thien-2-yl)propyl]pipéridine-3-carboxylique 2 5 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(3-méthyl -thien-2-yl)butyl] pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-methylthien-2-yl) propyl] piperidine-3-carboxylic acid acid ( 3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methyl-thien-2-yl) butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méîhoxyquinolm-4-yl)propyl]-1 -[2-(3-méthyl -thien-2-yl)thioéthyl]pipéndme-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [2- (3-methyl-thien-2-yl) thioethyl] piperid-3-carboxylic acid

Acide (3R,4R) -4-[3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-(3-méthyl -thien-2-yl)tbiopropyl]30 pipéridine-3-caiboxylique(3R, 4R) -4- [3- (6-Methoxyquolin-4-yl) propyl] -1- [3- (3-methyl-thien-2-yl) tbiopropyl] piperidine-3-caiboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinoUn-4-yl)propyl]-1 -[3-(thien-3-yl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinin-4-yl) propyl] -1- [3- (thien-3-yl) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(thien-3-yl)butyl]pipéridme-3-caiboxylique 3 5 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(thien-3-yl)thioéthyl]pipéridine-3 caiboxylique 12 0 2 2 20(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- (4- (thien-3-yl) butyl] piperidin-3-caiboxylic Acid Acid (3R, 4R) ) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-3-yl) thioethyl] piperidine-3-caiboxylic acid 12 0 2 2

Acide (3R,4R)-4-[3-(6-inéthoxyquinolin-4-yl)propyl3-l-[3-(thien-3-yl)thiopropyl]pipéridine- 3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) thiopropyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[3-(for-2-yl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinin-4-yl) propyl] -1- [3- (for-2-yl) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(fur-2-yl)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (fur-2-yl) butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(fur-2-yl)thioéthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (fur-2-yl) thioethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(fur-2-yl)thiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (fur-2-yl) thiopropyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méüioxyquinolin-4-yl)propyl]-l -[3-(fur-3-yl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (fur-3-yl) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(fur-3-yl)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (fur-3-yl) butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquin(..lin-4-yl)propyl]-l-[2-(ftir-3-yl)thioéthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquin (l-lin-4-yl) propyl] -1- [2- (tert-3-yl) thioethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(fur-3-yl)thiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (fur-3-yl) thiopropyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyqumolin-4-yl)propyl]-1-[3-( 1 -méthyl-pyrrol-2-yl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquolin-4-yl) propyl] -1- [3- (1-methyl-pyrrol-2-yl) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-( 1 -méthyl-pyrrol-2-yl)butyl]pipéridine-3-caiboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (1-methyl-pyrrol-2-yl) butyl] piperidine-3-caiboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-( 1 -méthyl-pyrrol-2-yl)thioéthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (1-methyl-pyrrol-2-yl) thioethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-( 1 -méthyl-pyrrol-2-yl)thiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (1-methyl-pyrrol-2-yl) thiopropyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-( 1 -méthyl-pyrrol-2-yl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (1-methyl-pyrrol-2-yl) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin^-yl)propyl]-1 -[4-( 1 -méthyl-pyrrol-3-yl)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-1-yl) propyl] -1- [4- (1-methyl-pyrrol-3-yl) butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-( 1 -méthyl-pyirol-3-yl)thioéthyl]pipéridine-3 -carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (1-methylpyrol-3-yl) thioethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-( 1 -méthyl-pyrrol-3-yl)thiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (1-methyl-pyrrol-3-yl) thiopropyl] piperidine-3-carboxylic acid

Acide (3R.4R)-4-[3-(6-mé±oxyquinolirM-yl)propyl]-1 -[3-( 1,3-thiazol-2-yl)propyl]pipéridine-3-carboxylique 21(3-4R) -4- [3- (6-Methyl-quinolimin-1-yl) propyl] -1- [3- (1,3-thiazol-2-yl) propyl] -piperidine-3-carboxylic acid 21

Acide (3R,4R)-4-(3-(6-méîhoxyquinolin-4-yl)propyl]-l-(4-(1,3-thiazol-2-yl)butyl]pipéridine- 3-caiboxylique(3R, 4R) -4- (3- (6-Methoxyquinolin-4-yl) propyl] -1- (4- (1,3-thiazol-2-yl) butyl] piperidine-3-caiboxylic acid

Acide (3R,4R)-4-(3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-( 1,3-thiazol-2-yl)thiopropyl]pipéridine-3-carboxylique 5 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(3-( l-méthyl-imida2ol-2-yl)propyl] pipéridine-3-caiboxylique(3R, 4R) -4- (3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl) thiopropyl] piperidine-3-carboxylic acid acid ( 3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (1-methyl-imidazol-2-yl) propyl] piperidine-3-caiboxylate

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1-(4-(1 -méthyl-imidazol-2-yl)butyl]pipéridine-3-caiboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- (4- (1-methyl-imidazol-2-yl) butyl] piperidine-3-caiboxylic acid

Acide (3R,4R)-4-(3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-( 1 -méthyl-imidazol-2-yl)thioéthyl]io pipéridine-3-caiboxylique(3R, 4R) -4- (3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (1-methylimidazol-2-yl) thioethyl] io-piperidine-3-caiboxylic acid

Acide (3R,4R)-4-(3-(6-méthoxyquinolin-4-yl)propyl]-l -(3-( 1 -méthyl-imidazol-2-yl)thiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- (3- (6-Methoxyquinolin-4-yl) propyl] -1- (3- (1-methyl-imidazol-2-yl) thiopropyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl-imidazol-4-yl)propyl]pipéridine-3-caiboxylique 15 Acide (3R,4R)-4-(3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(3-méthyl-imidazol-4-yI)butyl]pipéiidine-3-caiboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-imidazol-4-yl) propyl] piperidine-3-caiboxylic Acid ( 3R, 4R) -4- (3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methyl-imidazol-4-yl) butyl] piperidine-3-caiboxylic

Acide (3R,4R)-4-[3-(6-méihoxyquinolin-4-yl)propyl]-1 -[2-(3-méthyl-imidazol-4-yl)thioéthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methyloxyquinolin-4-yl) propyl] -1- [2- (3-methyl-imidazol-4-yl) thioethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l -(3-(3-méthyl-inùdazol-4-yl) 20 thiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- (3- (3-methyl-imidazol-4-yl) thiopropyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-mélhoxyqumolin-4-yl)propyl]- î -[3-(3-méthyl-pyrazol-4-yl)propyl]pipéi idine-3-carboxyIique(3R, 4R) -4- [3- (6-Methoxy-4-yl) propyl] -1- [3- (3-methyl-pyrazol-4-yl) propyl] piperidin-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(3-méthyl-pyrazol-4-yl)butyl]pipéridine-3-carboxylique 2 5 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -(2-(3-méthyl-pyrazol-4-yl)thioéthyl] pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (3-methyl-pyrazol-4-yl) butyl] piperidine-3-carboxylic acid Acid (3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- (2- (3-methyl-pyrazol-4-yl) thioethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-(3-(6-mëthoxyquinolin-4-yl)propyl]-1 -(3-(3-méthyl-pyra2ol-4-yl)thiopropyl)pipéridine-3-carboxylique(3R, 4R) -4- (3- (6-Methoxyquinolin-4-yl) propyl] -1- (3- (3-methyl-pyraol-4-yl) thiopropyl) piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinoliu-4-yl)propyl]-1 -[3-(oxazol-2-yl)propyl]pipéridine-3-30 carboxylique(3R, 4R) -4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [3- (oxazol-2-yl) propyl] piperidine-3-30 carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(oxazol-2-yl)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (oxazol-2-yl) butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(oxazol-2-yl)thioéthyl]pipéridine- 3-carboxylique 3 5 Acide (3R,4R)-4-(3-(6-méthoxyquinolin-4-yl)propyl]-1 -(3-(oxazol-2-yl)thiopropyl]pipéridine- 3-carboxylique 120 2 2 22(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (oxazol-2-yl) thioethyl] piperidine-3-carboxylic acid Acid (3R, 4R) ) -4- (3- (6-Methoxyquinolin-4-yl) propyl] -1- (3- (oxazol-2-yl) thiopropyl] piperidine-3-carboxylic acid 120 2 2 22

Acide (3R,4R)-4-[3-(6-niélhoxyquinolm-4-yl)propyl]-l -[3-(pyridin-2-yl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Niethyloxyquinol-4-yl) propyl] -1- [3- (pyridin-2-yl) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-{pyridin-2-yl)butyl]pipéridine-3-carboxylique 5 Acide (3R,4R)-4-[3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(pyridin-2-yl)thiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-2-yl) butyl] piperidine-3-carboxylic acid acid (3R, 4R) 4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [3- (pyridin-2-yl) thiopropyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-mé±oxyquinolin4-yl)propyl]-1 -[3-(pyridin-3-yl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methyl-quinolin-4-yl) propyl] -1- [3- (pyridin-3-yl) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(pyridin-3-yl)butyl]pipéridme-3-10 carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-3-yl) butyl] piperidin-3-10 carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyridin-3-yl)thioéthyl]pipéridme- 3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-3-yl) thioethyl] piperidin-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridm-3-yl)thiopropyl]pipéridine-3-carboxylique 15 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridin-4-yl)propyl]pipéridiiie-3- carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) thiopropyl] piperidine-3-carboxylic acid acid (3R, 4R) 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl) propyl] piperidiene-3-carboxylic acid

Acide (3R,4R)A-[3-(6-méthoxyquinolin-4- yl)propyl]-l-[4-(pyridin-4-yl)butyl]pipéridine-3-carboxylique(3R, 4R) -A- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-4-yl) butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin^-yl)propyl]-1 -[5-(pyridm-4-yl)pentyl]pipéridine-3-2 0 carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-1-yl) propyl] -1- [5- (pyrid-4-yl) pentyl] piperidine-3-carboxylic acid

Acide (3R.4R) A-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyridin-4-yl)thioéthyl]pipéridine-3-carboxylique(3R.4R) -A- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-4-yl) thioethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridin-4-yl)thiopropyl]pipéridine-3-carboxylique 2 5 Acide (3R,4R)-4-[3-(6-méthoxyquinolin4-yl)propylj-1 -[3-(pyrirnidin-2-yl)propyl]pipéridine- 3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl) thiopropyl] piperidine-3-carboxylic acid Acid (3R, 4R) ) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) propyl] piperidine-3-carboxylic acid

Acide (3R.4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(pyrimidin-2-yl)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidin-2-yl) butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyrimidin-2-yl)îhioéùyl] 3 o pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidin-2-yl) haloethyl] 3-piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-2-yl)thiopropyl]pipéridine-3-caiboxylique , Acide (3R_4R)-4-[3-(6-méthoxyquinolinA-yl)propyl]-1 -[3-(pyrimidin-4-yl)propyl]pipéridine- « 3-carboxylique 3 5 Acide (3R-4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-^yrirnidin-4-yl)butyl]pipéridrne-3- x carboxylique 23 120 2 2(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) thiopropyl] piperidine-3-caiboxylic acid, acid (3R_4R) -4 [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-4-yl) propyl] piperidine-3-carboxylic acid (3R-4R) -4- [3- (6) Methoxyquinolin-4-yl) propyl] -1- [4- (yrnidin-4-yl) butyl] piperidene-3-carboxylic acid 23 120 2 2

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyrimidin-4-yl)thioéthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidin-4-yl) thioethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]- l-[3-{pyriinidin-4-yl)thiopropyl]pipéridine-3-carboxylique 5 Acide (3R,4R)-4-[3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-(pyrimidin-5-yl)propyl]pipéridine- 3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyriinidin-4-yl) thiopropyl] piperidine-3-carboxylic acid acid (3R, 4R) 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-5-yl) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(pyrirnidin-5-yl)butyl]pipéridine-3·carboxylique . Acide (3R,4R)-4-[3-(6-méthoxyqumolm-4-yl)propyl3-1 -[2-(pyrimidin-5-yl)thioéthyl] 10 pipéridine-3-caiboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidin-5-yl) butyl] piperidine-3-carboxylic acid. (3R, 4R) -4- [3- (6-Methoxyqumol-4-yl) propyl] -1 - [2- (pyrimidin-5-yl) thioethyl] piperidine-3-caiboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(pyrimidin-5-yl)thiopropyl]pipéridine-3-caiboxylique(3R, 4R) -4- [3- (6-Methoxyquolin-4-yl) propyl] -1- [3- (pyrimidin-5-yl) thiopropyl] piperidine-3-caiboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrazin-2-yl)propyl]pipéridine-3-caiboxylique 15 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(pyrazin-2-yl)butyl]pipéndine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) propyl] piperidine-3-caiboxylic Acid Acid (3R, 4R) 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (pyrazin-2-yl) butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyrazin -2-yl)thioéthyl]pipéridine·3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (pyrazin-2-yl) thioethyl] piperidine · 3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrazin-2-yl)thiopropyl] 20 · pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) thiopropyl] 20-piperidine-3-carboxylic acid

Acide (3I<4R)-4-[3-(6-métiioxyquinolin-4-yl)propyl]-1 -[3-(pyridazin-3-yl)propyl]pipéridine-3-carboxylique(3 R <4R) -4- [3- (6-Methioxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyI]-l-[4-(pyridazin-3-yl)butyl]pipéridine-3·carboxylique 2 5 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propy!]-l-[2-(pyridazin-3-yl)thioéthyl] pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- (4- (pyridazin-3-yl) butyl] piperidine-3-carboxylic acid Acid (3R, 4R) 4 - [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridazin-3-yl) thioethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrida2in-3-yl)thiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl) thiopropyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-métboxyquinolin-4-yl)propyl]-1 -[3-(pyridazin-4-yl)propyl]pipéridine- 3 o 3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4-yl) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(pyridazin-4-yl)butylJpipéridme-3carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (pyridazin-4-yl) butyl] piperidin-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyndazin-4-yl)thioétliylj pipéridine-3-carboxylique 3 5 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridazin-4-yl)thiopropyl] pipéridine-3-carboxylique ^2022 24(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (pyndazin-4-yl) thioethyl) piperidine-3-carboxylic acid Acid (3R, 4R) 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4-yl) thiopropyl] piperidine-3-carboxylic acid 2022

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-fluoro-phényl)-prop-2-ynyl]-pipéridme-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-fluoro-phenyl) -prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R.4R)-4-[3-(6-méthoxyquinolin-4- yl)propyl]-1 -[3-(2-chloro-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3-4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-phenyl) -prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-chloro-phényl>prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-phenyl) prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[3-(4-chloro-phényl)-prop-2-ynyI]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methyl-oxyquinolin-4-yl) propyl] -1- [3- (4-chloro-phenyl) -prop-2-yl] -I-piperidine-3- acid carboxylic

Acide (3R,4R)-4-[3-(6-méîhoxyquinolin-4-yl)propyl]-1 -[3-(2-méthyl-phényl)-prop-2-ynyI]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-methyl-phenyl) -prop-2-yl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[3-(3-méthyl-phényl)-prop-2-ynyl]-pipéridine-3 -carboxylique(3R, 4R) -4- [3- (6-Methoxyquinin-4-yl) propyl] -1- [3- (3-methyl-phenyl) -prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R_4R)-4-[3-(6-méîhoxyquinolin-4-yl)propyl]-1 -[3-(4-méthyl-phényl)-prop-2-ynyl]-pipéridine-3 -carboxylique(3R_4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-methyl-phenyl) -prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4- [3-; 5-méihoxyquinolin—yl)propyl]-l-[3-(2-nifluoroméîhyl-pbenyl)-prop-2-ynyl]-pipéridù.e-3-carboxyliqueAcid (3R, 4R) -4- [3-; 5-méihoxyquinolin-yl) propyl] -l- [3- (2-nifluoroméîhyl-pbenyl) -prop-2-ynyl] -pipéridù.e-3-carboxylic acid

Acide (3R,4R)-4~L3-(6-méihox\’quinolin-4-yl)propyl]-1 -[3-(3-trif]uorométhy]-phényl)-prop-2-ynyl]-pipéndine-3 -carboxylique(3R, 4R) -4-L3- (6-Methyloxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethyl) phenyl) prop-2-ynyl] -piperine -3-carboxylic

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-trifluorométhyl-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethyl-phenyl) -prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R.4R)-4-[3-(6-méthox>'quinolin-4-yl)propyl]-1 -[3-(2-méthoxy-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxypinolin-4-yl) propyl] -1- [3- (2-methoxy-phenyl) -prop-2-ynyl] -piperidine-3-acid carboxylic

Acide (3R.4R)-4-[3-(6-méthoxyquinolin-4-vl)propyl]-1 -[3-(3-méthoxy-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxy-phenyl) -prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-vl)propy]3-l-[3-(4-méthoxy-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -3- [3- (4-methoxy-phenyl) -prop-2-ynyl] -piperidine-3-carboxylic acid

Acide ( 3R.4R)-4-[3-( 6-méthoxyquinolin-4-yl tpropyl]-1 -[?-( 3.4-difluoro-phényl)-prop-2-_\uyl]-pipéridine-3-carboxylique(3R4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1 - [? - (3,4-difluoro-phenyl) -prop-2-yl] -piperidine-3-carboxylic acid

Acide (3R.4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2.4-difluoro-phényl)-prop-2-yny]]-pipéridine-3-carboxylique(3R4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,4-difluoro-phenyl) -prop-2-yn]] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-vl ipropyl ]-1 -[3-(3.4-dichloro-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3,4-dichloro-phenyl) -prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R>4-[3-(6-méihoxyquînolin-4-yl)propyl]-1 -[3-(2.3-dichloro-phényl)-prop-2- ynyl ] -pipéridine-3 -carboxyliqu e(3R, 4R) 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichloro-phenyl) prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-{ 6-méthoxyquinolin-4-yl)propvl]-1 -[?-( 2.4-dichloro-phénvl)-prop-2- \uyl]-pipéridine-3-carboxylique 12022 25(3R, 4R) -4- [3- {6-Methoxyquinolin-4-yl) propyl] -1 - [? - (2,4-dichloro-phenyl) -prop-2-yl] -piperidine-3-carboxylic acid 12022 25

Acide (3R,4R)-4-[3-(6-métboxyquinolin-4-yl)propyl]-1 -[3-(2.4,6-trichloro-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trichloro-phenyl) -prop-2-ynyl] -piperidine-3- acid carboxylic

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3,5-dichloro-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3,5-dichloro-phenyl) -prop-2-ynyl] -piperidine-3- acid carboxylic

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-chloro-3-fluoro-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3-fluoro-phenyl) -prop-2-ynyl] -piperidine-acid 3-carboxylic acid

Acide (3R,4R)-4-[3-(6-niéthoxyquinolin-4-yl)propyl]- î -[3-(3-chioro-4-fluoro-phényî)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-4-fluoro-phenyl) -prop-2-ynyl] -piperidine-acid 3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-chloro4'fluoro-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4-fluoro-phenyl) -prop-2-ynyl] -piperidine-3- acid carboxylic

Acide (3R,4R)-4-[3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(3-chloro-5-fluoro-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquolin-4-yl) propyl] -1- [3- (3-chloro-5-fluoro-phenyl) -prop-2-ynyl] -piperidine-acid 3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-chloro-2-fluoro-phényl)-prop^2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-2-fluoro-phenyl) -propyl-2-ynyl] -piperidine-acid 3-carboxylic acid

Acide (3R,4R)-4-[3-(6-nïéthoxyquinoiin-4-yl)propyl]-1 -[3-(3-fluoro4-méthyl-phényl)-prop- 2-ynyl]-pipàidine-3-carboxyIique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-4-methyl-phenyl) -prop-2-ynyl] -pipaidine-3- acid carboxylic

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yi)propyl3-1 -[3-(4-chloro-3-trifluorométhy]-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3-trifluoromethyl) -phenyl) -prop-2-ynyl] -piperidine-acid 3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-chIoro-4-trifluorométhyl-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4-trifluoromethyl-phenyl) -prop-2-ynyl] -piperidine-acid 3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinoIin-4-yl)propy]]-1 -[3-(2-chloro-5-trifluoroméÎhyl-pbény])-prop-2-ynyl]-pipéridine-3-carboxyIique(3R, 4R) -4- [3- (6-Methoxyquinino-4-yl) propyl] -1- [3- (2-chloro-5-trifluoromethylbenzyl) prop-2-ynyl] - acid piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-rnéÜ)oxyqumolin-zl'yl)prop57l]'l-{3-(5-chioro-2-mé!}ioxy-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Fluoro) oxyquolin-2-yl) propyl] -1- {3- (5-chloro-2-methyl) phenyl) prop-2- acid; ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]' 1 -[3-(3,5-bis-trifluorométhyl-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3,5-bis-trifluoromethyl-phenyl) -prop-2-ynyl] -piperidine-acid 3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxy,quinolin-4-yl)propyl]-1 -[3-(3,5-diméthy}-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxy-quinolin-4-yl) propyl] -1- [3- (3,5-dimethyl-phenyl) -prop-2-ynyl] -piperidine Acid -3-carboxylic acid

Acide (3R4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl3-l-[3-(2,4-dichloro-6-méthyl-phényl)-prop-2-ynyl]-pipéridine-3-cart)Oxylique(3R4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,4-dichloro-6-methyl-phenyl) -prop-2-ynyl] -piperidine-3-acid -cart) Oxylique

Acide (3R,4R)-4-[3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[3-(5-chloro-thien-2-yl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinin-4-yl) propyl] -1- [3- (5-chloro-thien-2-yl) -prop-2-ynyl] -piperidine-acid 3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-chlorothien-2-yI)-prop-2-ynyl]- pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorothien-2-yl) prop-2-ynyl] piperidine-3- acid carboxylic

Acide (3R,4R)-4-[3-(6-méthoxyquinoiin-4-yi)propyi]-1 -[3-(5-méthyl-thien-2-yl)-prop-2- ynyl]^ipéridme-3-carboxylique 12 0 2 2 26(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthien-2-yl) prop-2-ynyl] etheride 3-carboxylic acid 12 0 2 2 26

Acide (3R,4R)^4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-mé±yl-thien-2-yl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-thien-2-yl) prop-2-ynyl] - acid piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thien-3-yl)-prop-2-ynyl]-pipéridine-3-carboxylique 5 Acide (3R,4R)-4-[3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[3-( 1 -méthyl-pyrrol-2-yl)-prop-2- ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop-2-ynyl] -piperidine-3-carboxylic acid (3R, 4R) -4- [3- (6-Methyl-quinolin-4-yl) propyl] -1- [3- (1-methyl-pyrrol-2-yl) -prop-2-ynyl] - acid piperidine-3-carboxylic acid

Acide (3R-4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-( 1 -méthyl-pyTrol-3-yl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R-4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (1-methyl-pyTrol-3-yl) -prop-2-ynyl] -piperidine-acid 3-carboxylic acid

Acide (3R,4R)-4-[3-(6-mé±oxyquinolin-4-yl)propyI]-1 -[3-( 1 ,3-thiazol-2-vl)-prop-2-ynyl]-10 pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methyl-oxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl) -prop-2-ynyl] - acid Piperidine-3-carboxylic acid

Acide (3R,4R)^-[3-(6-méthoxyqumolm-4-yl)propyl]-1 -[3-( 1.3-thiazol-4-yl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) - [3- (6-Methoxyqumol-4-yl) propyl] -1- [3- (1,3-thiazol-4-yl) -prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R.4R)^-[3-(6-méthoxyquinolin^4-yl)propyl]-1 -[3-( 1,3-thiazol-5-vl)-prop-2-\Tiy]]-pipéridine-3-carboxylique iAcide (3R_4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3 -( 1 -méthyl-imidazol-2-yl)-prop-2-ynyl]-pipéiidine-3-carboxylique(3R, 4R) 1- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-5-yl) prop-2-yl] -1-piperidine acid -3-carboxylic acid (3R- [4R] -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3 - (1-methyl-imidazol-2-yl) -prop-2-ynyl] - pipéiidine-3-carboxylic acid

Acide (3R_4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-méihyl-imidazoî-4-yl)-prop-2-ynvl]-pipéridine-3-carboxylique(3R_4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-imidazol-4-yl) -prop-2-yn] -1-piperidine-3- (3- (3-methoxyquinolin-4-yl) propyl] -piperidine-3- acid carboxylic

Acide f3R-4R)-4-[3-(6-méthoxyqumoLin-4-yl)propyl]-1 -[3-(3-méthyl-p\Tazol-4-yl)-prop-2-2 o ynyl]-pipéridine-3-carboxylique(3R-4R) -4- [3- (6-Methoxyquinyl-4-yl) propyl] -1- [3- (3-methyl-p-azol-4-yl) -prop-2-ynyl] -acid] -piperidine-3-carboxylic acid

Acide (3R-4R)-4-[3-(6-méthoxyquinolin^-yl)propyl]-1 -[3-(oxazoI-2-vl)-prop-2-ynyl]-pipéridine-3 -carboxylique(3R-4R) -4- [3- (6-Methoxyquinolin-1-yl) propyl] -1- [3- (oxazol-2-yl) -prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(oxazol-4-yl)-prop-2-ynyl]-pipéridine-3-carboxylique 2 5 Acide (3R.4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(oxazol-5-yl)-prop-2-yny]]- pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-4-yl) -prop-2-ynyl] -piperidine-3-carboxylic acid 2 (3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-5-yl) prop-2-yn]] - piperidine-3- acid carboxylic

Acide (3R4R)-4-[3-(6-méthoxyqujnolin-4-yî)propy]]-l-[3-(p\’ridin-2-y]')-prop-2-\,nyl]-pipendine-3-carbo\\ hque(3R4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (p-ridin-2-yl) prop-2-ynyl] acid - pipendine-3-carbo

Acide (3R-4R)-4-[3-<6-méthox\ quinolin-4-vl)propyl]-1 -[3-(,pyridin-3-yl )-prop-2-ynyl]- 3 o pipéndine-3-carboxylique(3R-4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1 - [3 - (, pyridin-3-yl) -prop-2-ynyl] -3-piperidine Acid -3-carboxylic acid

Acide (3R4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(p\-ridin-4-yl)-prop-2-\'nyl]-pipéndine- 3 -carboxylique(3R4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (p -ridin-4-yl) -prop-2-ynyl] -piperidine-3 -acid carboxylic

Acide i3R,4R)-4-[3-(6-mé±oxyquinolin-4-yl)propyl]-l-[3-(pyrimidin-2-yl)-prop-2-ynyl]- * pipéridine-3-carboxylique 3 5 Acide (3R.4R)-4-[3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-(p\Timidin^-yI)^prop-2-ynyl]- pipéridine-3-carboxylique 120 2 2 27I3R, 4R) -4- [3- (6-Methyl-quinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) -prop-2-ynyl] - piperidine-3- acid carboxylic acid (3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (p-Timidin-4-yl) prop-2-ynyl] piperidine 3-carboxylic acid 120 2 2 27

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-5-yl)-prop-2-ynyl]-pipéridine-3-caiboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-5-yl) prop-2-ynyl] -piperidine-3-caiboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyra2m-2-yl)-prop-2-ynyl]-pipéridine-3-carboxylique 5 Acide (3R,4R)-4-[3-(6-niéÎhoxyquinolin-4-yl)propyl]-l-(3-(pyridazin-3-yl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyra-2-yl) -prop-2-ynyl] -piperidine-3-carboxylic acid (3R, 4R) -4- [3- (6-Nienoxyquinolin-4-yl) propyl] -1- (3- (pyridazin-3-yl) prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyqumolin-4-yl)propyl]-1 -(3-(pyridazin-4-yl)-prop-2-ynyI]-pipéridine-3-carboxylique . Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-phénylbutèn-3-yl]pipéridine-3-10 cafboxylique(3R, 4R) -4- [3- (6-Methoxyquolin-4-yl) propyl] -1- (3- (pyridazin-4-yl) prop-2-yl] -1-piperidine-3-carboxylic acid. (3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4-phenylbuten-3-yl] piperidine-3-10 carboxylic acid

Acide (3R4R)-4-[3-(R,S)*hydroxy-3-(6-méthoxyquinolin-4-yI)propyl]-l-[4-phénylbutyl]pipéridine-3-carboxylique(3R4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4-phenylbutyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-(3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(3-(2-fluorophényl)propyl]pipéridine-3-carboxylique 15 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-rnéthoxyquinoiin-4-yl)propyl]-1 -(4-(2-fluorophényl) butyl]pipéridine-3-carboxylique(3R, 4R) -4- (3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (2-fluorophenyl) propyl] piperidine-3-carboxylic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (4- (2-fluorophenyl) butyl] piperidine-3- acid carboxylic

Acide (3R4R.)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyi]-l-[3-(3-fluorophény!)propyl]pipéridine-3-carboxylique(3R4R.) - 4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) propyl] piperidine-3- acid carboxylic

Acide (3R,4R)-4-[3-(RS)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(4-(3-fluorophényI)20 butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (4- (3-fluorophenyl) butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-(3-(R,S)-hydroxy-3-(6-métiioxyquinolin-4-yl)propyl]-1 -(3-(4-fluorophényl)propyl]pipéridine-3-caiboxylique(3R, 4R) -4- (3- (R, S) -hydroxy-3- (6-methioxyquinolin-4-yl) propyl] -1- (3- (4-fluorophenyl) propyl] piperidine-3- acid caiboxylique

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(4-(4-fluorophényl)butyl]pipéridine-3-carboxylique 2 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(3-(2,3- difluorophényl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (4- (4-fluorophenyl) butyl] piperidine-3- acid Carboxylic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (2,3-difluorophenyl) propyl) ] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(4-(2,3-difluorophényl)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (4- (2,3-difluorophenyl) butyl] piperidine-acid 3-carboxylic acid

Acide (3R,4R)-4-(3-(R-S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(3-(2,6- 3 o difluorophényi)propyl]pipéridine-3-carboxylique(3R, 4R) -4- (3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (2,6-difluorophenyl) propyl] piperidine acid 3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin4-yl)propyl]-1 -(4-(2,6-difluorophényl)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (4- (2,6-difluorophenyl) butyl] piperidine-3- acid carboxylic

Acide (3R,4R)j4-[3-(R,S)-bydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(3-(2-chlorophényl)propyl]pipéridine-3-carboxylique 3 5 Acide (3R,4R)-4-[3-(RS)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(4-(2-chlorophényl)butyl]pipéridine-3 -carboxylique 12ο 2 2 28(3R, 4R) 4- [3- (R, S) -bydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (2-chlorophenyl) propyl] piperidine-3-carboxylic acid (3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (4- (2-chlorophenyl) butyl] piperidine-3-acid - carboxylic acid 12ο 2 2 28

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(3-chlorophényl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (3-chlorophenyl) propyl] piperidine-3- acid carboxylic

Acide (3R,4R>4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(3-chlorophényl)butyl]pipéridine-3-carboxylique 5 Acide (3R,4R)-4-[3-(R-S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-{4-chlorophényl) propyl]pipéridine-3-carboxylique(3R, 4R) 4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-chlorophenyl) butyl] piperidine-3-carboxylic acid (3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (4-chlorophenyl) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(4-chlorophényî)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-chlorophenyl) butyl] piperidine-3- acid carboxylic

Acide (3R4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolinj4-yl)propyl]-1 -[3-(2.3- 1 o dichlorophényl)propyl]pipéridine-3-carboxylique(3R4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichlorophenyl) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)j4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(4-(2.3-dichlorophényl)buty4]pipéridine-3-carboxylique(3R, 4R) 4- [3- (R) S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (4- (2,3-dichlorophenyl) butyl] piperidine-3-carboxylic acid

Acide (3R4R)-4-[3-(RS}-hydroxy-3-(6-méthoxyquinolm-4-\4)propyl]-1 -(3-(2.6-dichlorophényl)propyl]pipéridine-3-carboxylique : 5 Acide (3R4R)-4-[3-(R.S)-hydro\y-3 -(6-méthoxyquinohn-4-y4)propyl]-1 -(4-(2.6- dichlorophényl)butyl]pipéri dii;e-3 -carboxylique(3R4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- (3- (2,6-dichlorophenyl) propyl] piperidine-3-carboxylic acid: 5 (3R4R) -4- [3- (RS) -Hydro-3 - (6-methoxyquinino-4-yl) propyl] -1- (4- (2,6-dichlorophenyl) butyl] piperedi-3-acid carboxylic

Acide (3R4R)-4-(3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-y4)propyl]-1 -(3-(2-méthylphényl)propyl]pipéridine-3-carboxylique(3R4R) -4- (3- (R) S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (2-methylphenyl) propyl] piperidine-3-carboxylic acid

Acide (3R4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(4-(2-méthylphényl) 2 0 buty l]pipéridine-3-carboxylique(3R4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (4- (2-methylphenyl) butyl] piperidine-3-acid carboxylic

Acide ('3R4R)-4-(3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[5-(2-méthylphényl')pentyl ]pipéridine-3 -carboxylique(3R4R) -4- (3- (R) S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [5- (2-methylphenyl) pentyl] piperidine-3-carboxylic acid

Acide (3R4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-l-yl)propyl]-l-[3-(3-méthy4phény4)propyl]pipéridine-3-carboxylique 2 5 Acide (3R.4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(4-(3-méthylphényl) butyl]pipéridine-3-carboxylique(3R4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-1-yl) propyl] -1- [3- (3-methyl-4-phenyl) -propyl] -piperidine-3-carboxylic acid Acid (3R4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (4- (3-methylphenyl) butyl] piperidine-3-carboxylic acid

Acide (3R.4R)-^[3-(KS)-hydroxy-3-(6-rnéthoxy quir)olin-4-yl')propyl]-1 -(3-(4-méthy4phényi)propy l]pipéndine-3-carboxyhque(3R4R) - [[3- (KS) -hydroxy-3- (6-methoxy-quinol-4-yl) propyl] -1- (3- (4-methylphenyl) propyl] piperidine-acid 3-carboxyhque

Acide (3R4R )-4-(3-( R.S)-hydrox\ -?-( 6-méthoxyquinolui-4-vl)propyl]-1 -[4-< 4-méthylphényl ) 3 ci buty4]pipéridine-3-carboxy4ique(3R4R) -4- (3- (RS) -Hydroxyl- (6-methoxyquinol-4-yl) propyl] -1- [4- (4-methylphenyl) butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yI)propyl]-1 -(3-(2-méthoxyphénvl )propyi jpipendine-3 -carboxylique ' Acide (3R.4R)-4-[3-(RS)-hydroxy-3-( 6-méthoxyquinolin-4-\ 1 )propyl]-1 -[4-( 2- méthoxyphény4)buty4]pipéridine-3-carboxylique 3 Ξ Acide (3R4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propylj-1 -(3-(3- méthoxyphényi )propy 4 jpipéridine-3-carboxylique 120 2 2 29(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (2-methoxyphenyl) propyl] pipendin-3-carboxylic acid (3R4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-methoxyphenyl) butyl] piperidine-3-carboxylic acid 3 (3R4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (3-methoxyphenyl) propyl] piperidine-3-carboxylic acid 120 2 2 29

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1-(4-(3- méthoxyphényl)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (4- (3-methoxyphenyl) butyl] piperidine-3- acid carboxylic

Acide (3R,4R)-4-[3-(R,S )-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(4- méthoxyphényl)propyl]pipéridine-3-caiboxyIique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (4-methoxyphenyl) propyl] piperidine-3- acid caiboxyIique

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(4- méthoxyphényl)butyl]pipéridine-3-cafboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-methoxyphenyl) butyl] piperidine-3- acid cafboxylique

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[3-(2- trifluorométhylphényl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethylphenyl) propyl] piperidine-3- acid carboxylic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthox\'quinolin-4-yl)propyl]-1 -[4-(2- trifluorométhylphényl)butyl]pipéridine-3<arboxyiique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoximinolin-4-yl) propyl] -1- [4- (2-trifluoromethylphenyl) butyl] piperidine acid -3 <arboxyiique

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthûxyquinolin-4-yl)propyl]-1 -[3-(3- trifluorométhylphényl)propyl]pipéridine-3-caiboxyIique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methylquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenyl) propyl] piperidine-3- acid caiboxyIique

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[4-(3- trifluoromé±ylphényi)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-trifluoromethylphenyl) butyl] piperidine acid; 3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méùioxyquinolin-4-yî)prüpyl]-1 -[3-(4- trifluorométhylphényl)propyl]pipéridine-3-carbcxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methioxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenyl) propyl] piperidine-3- acid carbcxylique

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(4- trifluoroméîhylphényl)butyl]pipéridme-3'Carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-trifluoromethylphenyl) butyl] piperidin-3 ' carboxylic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propylj-1 -[3-phénylthioéthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylthioethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-phénylthio-propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylthiopropyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydiOxy-3-(6-méihoxyquinolin-4-yî)propyl]-1 -[3-(2-fluorophénylthio)propyl]pipéridiiie-3-carboxylique(3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenylthio) propyl] piperidium-3- acid carboxylic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méÜioxyquinolin-4-yl)propyl]-1 -[3-(3-fluorophénylthio)propyl]pipéridine-3-carboxybque(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methyloxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenylthio) propyl] piperidine-3- acid carboxybque

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2-fluorophénylthio)étbyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (2-fluorophenylthio) ethyl] piperidine-3- acid carboxylic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(4-fluorophénylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-fluorophenylthio) ethyl] piperidine-3- acid carboxylic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[3-(4-fluorophénylthio)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenylthio) propyl] piperidine-3- acid carboxylic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin4-y])propyl]-1 -(2-(2,3-difluorophénylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (2- (2,3-difluorophenylthio) ethyl] piperidine-3-acid carboxylic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-mé±oxyquinolin-4-yl)propyl]-l-[3-(2,3-difluorophénylthio)propyl]pipéridine-3-carboxylique 120 22 30(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenylthio) propyl] acid piperidine-3-carboxylic acid 120 22 30

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[2-(2,6- difluorophénylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-difluorophenylthio) ethyl] piperidine-acid 3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin^-yl)propyl]-1 -[3-(2,6- difluorophénylthio)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-1-yl) propyl] -1- [3- (2,6-difluorophenylthio) propyl] piperidine-3-acid carboxylic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1-[2-(2- chlorophénylthio)éthyl]pipéridine-3-carbox>’lique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-chlorophenylthio) ethyl] piperidine-3- acid carbox> 'lic

Acide (3R,4R)^4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2- chlorophénylthio)propyl]pipéridine-3-carboxylique(3R, 4R) 4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenylthio) propyl] piperidine-3- acid carboxylic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méÎhoxyquinolin^-yl)propyl]-1 -[2-(3- chlorophénylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-1-yl) propyl] -1- [2- (3-chlorophenylthio) ethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm^-yl)propyl]-1 -[3-(3- chlorophénylthio)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-1-yl) propyl] -1- [3- (3-chlorophenylthio) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-mé±ox\'quinolm-4-yl)propyl]-1 -[2-(4- chlorophénylthio)é±yl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methyl-quinol-4-yl) propyl] -1 - [2- (4-chlorophenylthio) - acid ± yl] piperidine-3-carboxylic acid

Acide (3R_4R)-4-[3-(R.S » -hydroxy-3-(6-méihoxyquinolin^l-yl)propyl]-1 -[3-(4-chlorophénylüiio)prüpyl]pipéridine-3-carboxylique(3R_4R) -4- [3- (R) -NH-hydroxy-3- (6-methoxyquinolin-1-yl) propyl] -1- [3- (4-chlorophenylthio) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R_S)-hydroxy-3-(6-méthoxyquinolin4-yl)propyl]-1 -[2-(2.3-dichlorophénylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R-S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-dichlorophenylthio) ethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méÎhoxyquinolinA-yl)piOpyl]-1 -[3-(2,3- dichlorophénylÎhio)propyl]pipéridme-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) p-propyl] -1- [3- (2,3-dichlorophenylthio) propyl] piperidin-3- acid carboxylic

Acide (3R,4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin^-yl)propyl]-1 -[2-(2.6- dichlorophénylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R) S) -hydroxy-3- (6-methoxyquinolin-1-yl) propyl] -1- [2- (2,6-dichlorophenylthio) ethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2.6- dichlorophénylthio)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R) S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-dichlorophenylthio) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2- méthylphénylthio)éthy]]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R) S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methylphenylthio) ethyl]] piperidine-3-carboxylic acid

Acide f3R.4R)-4-[3-(R.S)-hydroxy-3-(6-mé±oxyquinolin-4-\T,propyl]-1 -f 3-( 2 - méihylp]iénylthio)prop\i]pipéridine-3-carboxyliqueF 3 R 4 R) -4- [3- (RS) -hydroxy-3- (6-methyl-4-oxyquinolin-4-propyl) -1- (3- (2-methylphenylthio) prop] piperidine-3-carboxylic acid

Acide (3R.4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3- méthylphénylthio)éthyl]pipéridine-3-carboxylique(3-4R) -4- [3- (R) S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylphenylthio) ethyl] piperidine-3-carboxylic acid

Acide i3R,4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)piOpyl]-1 -[3-(3 - mé±ylphénylthio)propyl]pipéridine-3-carboxYlique1 R, 4 R) -4- [3- (R) S) -hydroxy-3- (6-methoxyquinolin-4-yl) piOpyl] -1- [3- (3-methyl-phenylthio) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R_S )-hydroxyv3-(6-mérhoxyquinolin-4-yl)propyl]-1 -[2-(4- méthylphénylthio)éthyl]pipéridineL3-carbox>'lique(3R, 4R) -4- [3- (R) S -hydroxy) -3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methylphenylthio) ethyl] piperidine] -3-carboxic acid

Acide i3R,4R)-4-[3-(R.S)-hydroxy-3-(6-mé±oxyquinolin-4-yl)propy]]-1 -[3-(4- méthylphénylthio)prop>i]pipéridinè-3-carboxylique 31 12 0 2 2I3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenylthio) propyl] piperidinic acid; 3-carboxylic acid 31 12 0 2 2

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1-[2-(2- trifluorométhylhénylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-trifluoromethyl-phenylthio) ethyl] -piperidine-3- acid carboxylic

Acide (3R,4R)^-[3-(R,S)-hydroxy-3-(6-niéthoxyquinolin-4-yl)propyl]-1 -[3-(2- trifluroméihylphénylthio)propyl]pipéridme-3-caiboxylique 5 Acide (3R,4R)-4-[3-(R,S)-hydiOxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3- trifluorométhylphényltbio)éthyl]pipéridine-3-carboxyliqueAcide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-triflurométhylphénylthio)propyl]pipéridine-3-carboxyliqueAcide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yI)propyl]-1 -[2-(4- 10 trifluorométhylphénylthio)éthyl]pipéridme-3-caiboxylique(3R, 4R) 1- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethylphenylthio) propyl] piperidin-3-caiboxylic acid (3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethylphenylthio) ethyl] piperidine-3-acid Carboxylic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluromethylphenylthio) propyl] piperidine-3 Carboxylic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [2- (4-trifluoromethylphenylthio) ethyl] piperidine; 3-caiboxylique

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[3-(4-triflurométhyIphénylthio)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinin-4-yl) propyl] -1- [3- (4-trifluromethylphenylthio) propyl] piperidine-3- acid carboxylic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoiin-4-yI)propyl]-1 -[2-(2-méthoxyphénylthio)éthyl]pipéridine-3-caiboxylique 15 Acide (3R4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-y])piOpyl]-1 -[3-(2-méthoxyphénylthio)propyl]pipéridine-3-caiboxyUqueAcide (3R4R)-4-[3 •(R,S)-hydroxy-3-(6-méthoxyquinolin-4-y])propyl]-1 -[2-(3-méthoxyphénylthio)éthyl]pipéridine-3-carboxyliqueAcide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3- 2 o méthoxyphénylthio)propyl]pipéridme-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methoxyphenylthio) ethyl] piperidine-3- acid caiboxylic acid (3R4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) p-propyl] -1- [3- (2-methoxyphenylthio) propyl] piperidine-3-caiboxy Acid (3R4R) -4- [3 • (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methoxyphenylthio) ethyl] piperidine-3-carboxylic acidAcid ( 3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenylthio) propyl] piperidin-3- carboxylic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(4-méthoxyphénylthio)éthyl]pipéridine-3-carboxybque(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methoxyphenylthio) ethyl] piperidine-3- acid carboxybque

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-méthoxyphényîthio)propyl]pipéridine-3-carboxylique 2 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[cyclopropylméthyl] pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenylthio) propyl] piperidine-3- acid carboxylic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclopropylmethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(cycîopropyl)éthyl]pipéridine-3-carboxybque(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopropyl) ethyl] piperidine-3-carboxybucoic acid

Acide (3R,4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[cyclobutylméthyl] 3 o pipéridine-3-carboxylique(3R, 4R) -4- [3- (R) S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [cyclobutylmethyl] 3-piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yi)propylj-1 -[2-(cyclobutyl)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclobutyl) ethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[cyclopentylméthyl]pipéridine-3-carboxylique 3 5 Acide (3R,4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinoiin-4-yl)propyl]- l-[2-(cyclopentyl)éthyl]pipéridine-3-carboxylique 32(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclopentylmethyl] piperidine-3-carboxylic acid acid (3R, 4R) 4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentyl) ethyl] piperidine-3-carboxylic acid 32

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[cyclohexylméthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [cyclohexylmethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propylj-1 -[2-(cyclohexyl)éthyl]pipéridine-3-carboxyhque(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-3-carboxylic acid

Acide (3R.4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(cyclopropylthio)éthyl]pipéridine-3-carboxylique(3-4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopropylthio) ethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(cyclopropylthic)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopropylthic) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(cyclobutylthio)éthyl]pipéridine-3-carboxyhque(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclobutylthio) ethyl] piperidine-3-carboxyhc acid

Acide (3R-4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(cyclobutylthio-propyl]pipéridme-3-carboxylique(3R-4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (cyclobutylthio-propyl) piperidin-3-carboxylic acid

Acide (3R,4R)^4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(cyclqpentylthio)éthyl]pipéridine-3 -carboxylique(3R, 4R) 4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopropylthio) ethyl] piperidine-3-carboxylic acid

Acide (3R.4R)-4-[3-(R,S)-hvdroxy-3-(6-méthoxyquinolin-4 yl)propyl]-1 -[3-(cyclopentylthio)propyl]pipéridine-3-carboxyhque(3-4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopentylthio) propyl] piperidine-3-carboxyhydroxybasic acid

Acide (3R_4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]- l-[2-(c\ clohexylthio)éthyl]pipéridine-3-carboxylique(3R_4R) -4- [3- (R) S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperidine-3-carboxylic acid

Acide (3R.4R)-4-[3-(R-S)-hydroxy-3-(6-méthox\'quinolin^}-yl)propyl]-1 -[3-(cyclohexylthio)propyl]pipéridine-3-carboxylique4- (3- (R-S) -hydroxy-3- (6-methoxyminolin-1-yl) propyl] -1- [3- (cyclohexylthio) propyl] piperidine-3-carboxylic acid

Acide (3R.4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-méthylthioéthyl]pipéridine-3 -carboxylique(3-4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-methylthioethyl] piperidine-3-carboxylic acid

Acide (3R.4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-méthvlthio-propyl]pipéridine-3-carboxylique(3-4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-methylthiopropyl] piperidine-3-carboxylic acid

Acide (3R.4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxvquinolin-4-yl)propyl]-1 -[2-éthylthioéthyl]pipéridine-3 -carboxylique(3-4R) -4- [3- (R, S) -hydroxy-3- (6-methoxvquinolin-4-yl) propyl] -1- [2-ethylthioethyl] piperidine-3-carboxylic acid

Acide (3R.4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinokn^-yl)propyl]-1 -[3-éthylthiopropvl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R) S) -hydroxy-3- (6-methoxyquinyl-4-yl) propyl] -1- [3-ethylthiopropyl] piperidine-3-carboxylic acid

Acide (3R-4R)-4-[3-(R,S)-h\droxy-3-( 6-méthoxyquinoim-4-yl)propyl]-l-[2-(n-propylthio')éthyl]pipéridine-3-carboxylique(3R-4R) -4- [3- (R, S) -H -xy-3- (6-methoxyquinoim-4-yl) propyl] -1- [2- (n-propylthio) ethyl] piperidine acid -3-carboxylic acid

Acide (3R.4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]- l-[3-(n-propvlthio)propyl]pipéridine-3-carboxvlique(3R, 4 R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (n-propylthio) propyl] piperidine-3- acid carboxylic

Acide (3R.4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyqujnolin-4-yl Jpropyl]-1 -[2-(n-butylthio) éthvl]pipéridine-3-carboxylique *(3R4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (n-butylthio) ethyl] piperidine-3-carboxylic acid *

Acide (3R.4R)-4-[3-(R.S)-hydroxy-3-(6-méthox\quinohn-4-yl)propyl]-1 -[3-(n-butvlthio) propvl]pipéndine-3-carboxylique x 120 22 33(3R4R) -4- [3- (RS) -Hydroxy-3- (6-methoxino-4-yl) propyl] -1- [3- (n-butylthio) propyl] piperidine-3- acid carboxylic acid x 120 22 33

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-y{)propyI]- l-[3-(thien-2-yl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (thien-2-yl) propyl] piperidine acid -3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[4-(thien-2-yl)buiyljpipéridme-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-2-yl) -biperyl] piperidinic acid carboxylic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méîhoxyquinolin-4-yl)propyl]-1 -[3-(thien-2-yl)thiopropyl]pipéridine-3-carbox\’lique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) thiopropyl] piperidine acid 3-carbox \ lic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(5-chloro-thien- 2-yl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (5-chloro-thien-2-yl) acid propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(5-chIoro-thien-2-yl)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [4- (5-chloro-thien-2-yl) acid butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(5-chloro-thien-2-yl)thioéthyl]pipéridine-3-caiboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (5-chloro-thien-2-yl) acid thioethyl] piperidine-3-caiboxylique

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(5-chloro-thien-2-yl)tbiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (5-chloro-thien-2-yl) acid tbiopropyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinûlin-4-yl)propyl]-1 -[3- (3-chloro-thien-2-yl)piOpyl]pipéridine-3-caiboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-thien-2-yl) acid) piOpyl] piperidin-3-caiboxylique

Acide (3R,4R)-4-[3-(R.S)-hydroxy-3-(6-métboxyquinolin-4-yl)propyl]-1 -[4-(3-chloro-thien-2-yl)butyl]pipéridine-3 -carboxylique(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-metboxyquinolin-4-yl) propyl] -1- [4- (3-chloro-thien-2-yl) butyl] acid Piperidine-3-carboxylic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propylj-1 -[2-(3-chloro-thien-2-yl)îhioéthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chloro-thien-2-yl) methyl] ethyl acid ] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-chloro-thien-2-yl)îhiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-chloro-thien-2-yl) acid îhiopropyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxy'quinolin-4-yl)propyl]- l-[3-(5-méthyl -thien-2-yl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthien-2-yl) -acrylic acid; yl) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[4-(5-méthyl -thien-2-yl)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1 - [4- (5-methylthien-2-yl) acid butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[2~(5-méthyl -thien-2-yl)thioéthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2 - (5-methylthien-2-yl) thioethyl] acid piperidine-3-carboxylic acid

Acide (3Rt4R)-4-[3-(R?S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(5-méthyl -thien-2-yl)tHopropyl]pipéridine-3-carboxylique(3Rt4R) -4- [3- (R3 S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthien-2-yl) tHopropyl] acid piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[3-(3-méthyl -thien-2-yl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylthien-2-yl) propyl] acid piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(3-méthyl -thien- 2-yl)butyl]pipéridine-3-caiboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylthien-2-yl) acid butyl] piperidine-3-caiboxylique

Acide (3R,4R)-4-[3-(R_S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3-méthyl -thien- 2 -yl)thioéthyl]pipéridine-3 -carboxylique 34(3R, 4R) -4- [3- (R-S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylthien-2-yl) thioethyl] acid Piperidine-3-carboxylic 34

Acide (3R,4R)^4-[3-(R,S)-hydroxy-3-(6-mé±oxyquinoL-i-4-yl)propyl]-l-[3-(3-méthyl -thien-2-yl)tbiopropyl]pipéridine-3-carboxylique(3R, 4R) 4- [3- (R, S) -hydroxy-3- (6-methyloxyquinol-4-yl) propyl] -1- [3- (3-methyl) -thienic acid; 2-yl) tbiopropyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoln-4-yl)propyl]-1 -[3-(thien-3-yl)propyl]pipéridine-3-carboxylique 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinobn-4-yl)propyl]-1 -[4-(thien-3- yl)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (thien-3-yl) propyl] piperidine acid 3-carboxylic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinob-4-yl) propyl] -1- [4- (thien-3-yl)) butyl] piperidine-3-carboxylic acid

Acide (3R4R)-4-[3-CRS)-hydroxy-3-f6-méthoxyquinolin-4-yi)propyl]-1 -[2-(thien-3-yl)thioéîhyl]pipéridine-3-caiboxylique(3R4R) -4- [3-CRS) -hydroxy-3-β-methoxyquinolin-4-yl) propyl] -1- [2- (thien-3-yl) thioheyl] piperidine-3-caiboxylic acid

Acide (3R,4R)-4-[3-(R-S)-hydroxy-3-(6-méthoxyqumo?ii-4-yl)propyl]-l-[3-(thjen-3-IO yl)thiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxy-4-yl) propyl] -1- [3- (thien-3-10-yl) thiopropyl] piperidine acid -3-carboxylic acid

Acide (3R,4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyqumoùn^-yl)propyl]-1 -[3-(fur-2-yl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R) S) -hydroxy-3- (6-methoxyquinyl-1-yl) propyl] -1- [3- (fur-2-yl) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinoin-4-yl)propyl]-l-[4-(fiir-2- ·yl)buÎyl]pipéridine-3-carboxylique 2 5 Acide f3R.4R)-4-[3-(R.S)-hydrox\'-3-(,6-méthoxyquinciin-4-yl)propyrj- i -[2-(fur-2-j ·1)±ίοέών1]ρίρέιίάιηέ-3-ΰ3Γί,Όλ7ΐιςυε(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinoin-4-yl) propyl] -1- [4- (1-flu-2-yl) -benzyl] piperidine acid Carboxylic acid f 3 R 4 R) -4- [3- (RS) -hydroxyl] -3 - (, 6-methoxyquinin-4-yl) propyl] -2- (fur-2-y) ) ± ίοέών1] ρίρέιίάιηέ-3-ΰ3Γί, Όλ7ΐιςυε

Acide (3R,4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin^4-yl)propyl]-1 -[3-(fur-2-yl)thiopropyl]pipéridine-3-carbox7lique(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-2-yl) thiopropyl] piperidine-3- acid carbox7lique

Acide (3R,4R)^-[3-(R,S)-hydroxy-3-(6-mé±oxyquinolin-4-yl)propyl]-l-[3-(fur-3-2 o yl)propyl]pipéridine-3-carboxylique(3R, 4R) - [3- (R, S) -hydroxy-3- (6-methyloxyquinolin-4-yl) propyl] -1- (3-fur-3-yl) propyl acid ] piperidine-3-carboxylic acid

Acide (3R,4R)-^-[3-(R.S)-hydrox7-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[4-(fur-3-vl)butyl]pipéridine-3-carboxylique(3R, 4R) - N - [3- (RS) -Hydrox) -3- (6-methoxyquinol-4-yl) propyl] -1- [4- (fur-3-yl) butyl] piperidine-3- acid carboxylic

Acide (3R4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[2-(fùr-3-yl)thioéthyl]pipéridine-3-carboxylique 2 5 Acide (3R,4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinohn-4-yl)propyl]-1 -[3-(fiir-3- vl )thiopropyl]pipéridine-3 -carboxylique(3R4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [2- (fr-3-yl) thioethyl] piperidine-3-carboxylic acid 2 (3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxy-quinolin-4-yl) -propyl] -1- [3- (1-flu-3-yl) thiopropyl] piperidine-3-acid carboxylic

Acide (3R.4R)-4-[3-(R.S)-hvdrox\-3-( 6-méthoxyquinolin-4-yl)propyl]-1 -[3-( 1 -méthyl-pyrrol-2-yl)prop\'l]pipéridine-3-carbox\lique(3R4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methyl-pyrrol-2-yl) propanic acid \ 'l] piperidine-3-carbox \ lic

Acide (3R.4R i-4-[3-(R.S )-hydroxy-3-( 6-méthox\quinolin-4-yl)propyl]-1 -[4-f ] -méthyl-pyrrol- 3 o 2-yl)butyl]pipéridiue-3-cafboxylique(3R4R) -I- 4- [3- (RS) -hydroxy-3- (6-methoxylquinolin-4-yl) propyl] -1- [4-f] methyl-pyrrol-3-2- acid yl) butyl] pipéridiue-3-cafboxylique

Acide (3R_4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[2-( 1 -méthyl-pyrrol-2-yl)thioéihyl]pipéridine-3-carboxylique , Acide (3R,4R)-4~[3-(R_S J-hydroxy-3-(6-méîhoxyquinolin-4-yl)propyl]-1 -[3-( 1 -méthyl-pyrrol-« 2 -yl Ithiopropyl ]pipéridine-3 -carboxyl ique 3 5 Acide (3R,4R)-4-[3-(R.S)-hydrox\’-3-(6-mé±oxyquinolin-4-\l)propyl]-1 -[3-( 1 -méthvl-pyrrol-x 2 -yl)propyl]pipéridine- 3 -carboxylique 35(3R_4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1-methyl-pyrrol-2-yl) thioheyl] piperidine acid 3-Carboxylic acid, (3R, 4R) -4- [3- (R) -S-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methyl-pyrrol) -2- -yl Ithiopropyl] piperidine-3-carboxylic acid (3R, 4R) -4- [3- (RS) -hydroxy] -3- (6-methoxyquinolin-4-yl) propyl] -1 [3- (1-Methyl-pyrrol-x 2-yl) propyl] piperidine-3-carboxylic 35

Acide (3R,4R)-4-[3-(R.S)-hydroxy-3-{6-méthoxyquinolin-4-yl)propyl]-1 -[4-( 1 -méthyl-pyrrol- 3-yl)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1-methyl-pyrrol-3-yl) butyl] acid piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-( 1 -méthyl-pyrrol- 3-yl)thioéthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1-methyl-pyrrol-3-yl) acid) thioethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-( 1 -méthyl-pyrrol-3-yl)thiopropyI]pipéridine-3-carboxyIique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (1-methyl-pyrrol-3-yl) acid thiopropyI] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-ÇRS)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 - [3-( 1,3-tbiazol-2-yl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3-CRS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-tbiazol-2-yl) propyl] piperidine acid -3-carboxylic acid

Acide (3R,4R)-4-[3-(RS)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[4-( 1,3-thiazoî-2-yl)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1,3-thiazol-2-yl) butyl] acid piperidine-3-carboxylic acid

Acide (3R,4R)4-[3-(RS)-hydroxy-3-(6-niéthoxyquinolin-4-yl)propyl]-l-[3-(l;3-thiazol-2-yl)thiopropyl]pipéridine-3-caiboxylique(3R, 4R) 4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl) thiopropyl] piperidine acid -3-caiboxylique

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[3~( 1 -méîhyl-imidazol-2-yl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3 - (1-methyl-imidazol-2-) -acidazol yl) propyl] piperidine-3-carboxylic acid

Acide (3R4R)-4-[3-(RS)-hydro.xy-3-(6-mét}ïOxyquinolin-4-yl)propyl]-l-[4-(l-méthyl-inudazol-2-yl)butyl]pipàidme-3-carboxylique(3R4R) -4- [3- (RS) -Hydroxy-3- (6-methyl) -quinolin-4-yl) propyl] -1- [4- (1-methyl-in-zuzol-2-yl) -acid butyl] pipàidme-3-carboxylic acid

Acide (3R,4R)-4-[3-(RS)-hydroxy-3-(6-méihoxyquinolin-4-yl)piOpyl]-1 -[2-( 1 -méthyl-imidazol-2-yl)thioéîhyl]pipèndme-3 -carboxylique(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) p-propyl] -1- [2- (1-methyl-imidazol-2-yl) thioheyl] acid Piperme-3-carboxylic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-( 1 -méthyl-imidazoî-2-yl)thiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methyl-imidazol-2-yl) acid) thiopropyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-méthyl-imida2ol-4-yl)propyl]pipéridine-3-carboxyl’que(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-imidazol-4-yl) propyl] acid piperidin-3-carboxyl'que

Acide (3R,4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(3-méthyl-imidazol-4-yl)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylimidazol-4-yl) butyl] acid piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(3-méthyl-imjda2ol-4-yl)thioéthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methyl-imidazol-4-yl)) acid thioethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl-imidâ2ol-4-yl)tluopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-methyl-imidazol-4-yl) acid tluopropyl] piperidine-3-carboxylic acid

Acide (3Ri4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yI)propyl]-1 -[3-(3-méthyl-pyrazol-4-yî)propyl]pipéridine-3-carboxylique(3R14R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-pyrazol-4-yl) propyl] piperidine-acid 3-carboxylic acid

Acide (3R,4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(3-méthyl-pyrazol-4-yl)butyl]pipéridme-3-carboxylique(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methyl-pyrazol-4-yl) butyl] acid pipéridme-3-carboxylic acid

Acide (3R.4R)-4-[3-(KS)-hydroxy-3-(6-méthoxyquinolin-4-yl)propylj-1 -[2-(3-méthyl- pvrazol-4-yl)thioéthyl ]pipéridine-3 -carboxylique(3R4R) -4- [3- (KS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylprazol-4-yl) thioethyl] piperidine acid -3-carboxylic

Acide (3R,4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-méthyl- pyrazol-4-yl)thiopropyl jpipéridine- 3 -carboxylique 120 2 2 36 10(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylpyrazol-4-yl) thiopropyl] piperidine acid - 3-carboxylic acid 120 2 2 36 10

2C2C

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyqxiinolin-4-yl)propyl]-1 -[3-(oxazol-2-yl)propyl]pipéridine-3-caiboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxy-quinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) propyl] piperidine-acid 3-caiboxylique

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(oxazol-2-yl)butyl]pipéridine-3-caiboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (oxazol-2-yl) butyl] piperidine-acid 3-caiboxylique

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm^-yI)propyl]-1 -[2-(oxazol-2-yl)thioéthyl]pipéridme-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-1H) propyl] -1 - [2- (oxazol-2-yl) thioethyl] piperidin-3-acid carboxylic

Acide (3R,4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(oxazol-2-yl)thiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) thiopropyl] piperidine-3- acid carboxylic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin^-yl)propyl]-1 -[3-(pyridin-2-yl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-1-yl) propyl] -1- [3- (pyridin-2-yl) propyl] piperidine-3-acid carboxylic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propylj-1 -[4-(pyridin-2-yl)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-2-yl) butyl] piperidine-3-acid carboxylic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoLin-4-yl)propyl]-1 -[3-(pyridin-2-yl)thiopropyl]pipéridme-3<arboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) thiopropyl] piperidine acid; 3 <arboxylique

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(ô-méthoxyquinolin-4-yl)prqpyl]-1 -[3-(pyridin-3-vl)propyl]pipéridine -3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl) propyl] piperidine acid - 3-carboxylic acid

Acide (3R,4R)-4-[3-(R_S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[4-Çpyridin-3-yl)butyl]pipéridine-3-carboxvlique(3R, 4R) -4- [3- (R) S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- (4-pyridin-3-yl) butyl] piperidine-3-carboxylic acid

Acide (3R,4R)A-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyridin-3-yl)thioéthyl]pipéridine-3-carboxylique(3R, 4R) -A- [3- (R) S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-3-yl) thioethyl] piperidine-3-carboxylic acid

Acide (3R,4R)^-[3-(KS)-hydroxy-3-(6-méthoxyquinolm-r-y]')propyl]-1 -[3-(pyridin-3-y])thiopropyl]pipéridine-3-carboxylique(3R, 4R) 1- [3- (KS) -hydroxy-3- (6-methoxyquinol-1-yl) propyl] -1- [3- (pyridin-3-yl) thiopropyl] piperidine-3- acid carboxylic

Acide (3R,4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridin-4-yl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl) propyl] piperidine-3- acid carboxylic

Acide (3R,4R)^4-[3-(R.S)-hydroxy-3-(6-métiioxyquinolin-4-yl)propyl]-1 -[4-(pvridin-4-yl)butyl]pipéridine-3-carboxvlique(3R, 4R) 4- [3- (RS) -hydroxy-3- (6-methioxyquinolin-4-yl) propyl] -1- [4- (pvidin-4-yl) butyl] piperidine-3- acid carboxylic

Acide (3R.4R)-4-[3-(R.S)-hydroxy-3-( 6-méthoxyquinolin-4-yl)propy]]- l-[5-(pvridin-4-yl ,penÎyl]pipéridine-3-carboxylique(3R4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [5- (pyridin-4-yl) -piperidyl] -3-piperidine acid carboxylic

Acide (3R.4R)^-[3-(R-S)-h\-droxy-3-(6-méthoxyquinolin-4-yl)propylJ-1 -[2-(pyridm-2-yl)thioéthyl]pipéridine-3-caiboxylique(3R4R) - [3- (RS) -H-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (pyrid-2-yl) thioethyl] piperidine-3-acid -caiboxylique

Acide (3R.4RH-[3-(R. S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyridin-4-yl )ihioéthvl]pipéndine-3-carboxylique(3R4RH- [3- (R. S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-4-yl) thioethyl] piperidine-3-carboxylic acid

Acide (3R.4R)-4-[3-(RS)-hydroxy-3-(6-méthoxyquinolin-4-yl)propy]]-1 -[3-(pyridin-4-yl)thiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl) thiopropyl] piperidine-3-acid carboxylic

Acide (3R,4R)-4-[3-(R.S)-hydroxy-3-(6-métho?cyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-2-yl )propyl]pipéridine-3-carboxyliqùe 12 0 2 2 37(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) propyl] piperidine acid 3-carboxylic acid 12 0 2 2 37

Acide (3R4R)-4-[3-(R,S}-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(pyrimidin-2-yl)butyl]pipéridine-3-carboxylique(3R4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidin-2-yl) butyl] piperidine-3- acid carboxylic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méîhoxyquinoiin-4-yl)propyl]-l -[2-(pyrimidin-2-yl)thioéihyl]pipéridine-3-carboxylique 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-2- yl)1hiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (pyrimidin-2-yl) thioheyl] piperidine acid 3-carboxylic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) 1hiopropyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]- l-[3-(pyrimidin-4-yl)propyl]pipéridine-3-caiboxyIique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-4-yl) propyl] piperidine acid 3-caiboxyIique

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-{pyrimidin-4-io yl)butyl]pipéridine-3-carboxyEque(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidin-4-yl) butyl] piperidine acid -3-carboxyEque

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoEn-4-yl)propyî]- l-[2-(pyrimidin-4-yl)thioéthyl]pipéridine-3-carboxyIique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinin-4-yl) propyl] -1- [2- (pyrimidin-4-yl) thioethyl] piperidine acid; 3-carboxylic acid

Acide (3R,4R')-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidm-4-yl)thiopropyl]pipéridme-3-caiboxylique 15 Acide (3R,4R)^-[3-(R,S)-hydro.<y-3-(6-méthoxyquinoEn^-yl)propyl]-1 -[3-(pyrimidin-5-yl)propyl]pipéridme-3-carboxylique(3R, 4R ') - 4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimid-4-yl) thiopropyl] piperidinic acid -3-Caiboxylic acid (3R, 4R) 1- [3- (R, S) -hydroxy-3- (6-methoxyquinyl-1-yl) propyl] -1- [3- (pyrimidin-5- yl) propyl] pipéridme-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyqujnoiin-4-yî)propyl]-1 -[4-(pyrimidin-5-yl)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinyl-4-yl) propyl] -1- [4- (pyrimidin-5-yl) butyl] piperidine-acid 3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyrimidm-5-2 O yl)thioéthyî]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidin-5-yl) thioethyl] acid piperidine-3-carboxylic acid

Acide (3R,4R)A-[3-(R,S)-hydroxy-3-(6-méthoxyquinoEn-4-yl)propyl]-1 -[3-(pyrimidin-5-yl)thiopropyl]pipéridine-3-carboxylique(3R, 4R) -A- [3- (R, S) -hydroxy-3- (6-methoxyquinin-4-yl) propyl] -1- [3- (pyrimidin-5-yl) thiopropyl] piperidine-3-acid carboxylic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoEn-4-yl)propyl]-1 -[3-(pyrazin-2-yl)propyl]pipéridine-3-carboxylique 2 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(pyrazin-2- yl)butyl]pipéridine-3 -carboxyEque(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinin-4-yl) propyl] -1- [3- (pyrazin-2-yl) propyl] piperidine acid 3-carboxylic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrazin-2-yl) ) butyl] piperidine-3-carboxylicEque

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoEn-4-yl)propyl]-l -[2-(pyrazin -2-y])thioéthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinin-4-yl) propyl] -1- [2- (pyrazin-2-yl) thioethyl] piperidine acid -3-carboxylic acid

Acide (3R,4R)A-[3-(R,S)-hydroxy-3-(6-méthoxyqmnolin-4-yl)propyl]-1 -[3-(pyrazin-2-30 yl)thiopropyl]pipéridine-3-carboxylique(3R, 4R) -A- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) thiopropyl] piperidine acid 3-carboxylic acid

Acide (3R,4R)“4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridazin-3-yl)propyl]pipéridine-3-carboxylique4- (3- (3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) propyl] piperidine acid (3R, 4R) 3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(pyridazin-3-yl)butyl]pipéridine-3-carboxvlique 3 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyridazin-3- yi)Îhioéthyl]pipéridine-3-carboxylique 12022 38(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridazin-3-yl) butyl] piperidine acid 3-Carboxylic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridazin-3-yl) ) 1Hioethyl] piperidine-3-carboxylic acid 12022 38

Acide (3R,4R)-4-[3-(R,S>hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridazin-3-yl)thiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) thiopropyl] piperidine-3 acid carboxylic

Acide (3R,4R)^-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridazin-4-yl)propyl]pipéridine-3-carboxy’lique 5 Acide (3R4R)-4-[3-(RS)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(pyridazin-4-yl)buîyl]pipéridine-3-carboxylique(3R, 4R) - [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4-yl) propyl] piperidine-3-carboxy acid (3R4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridazin-4-yl) methyl] piperidine-3-acid carboxylic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyridazin-4-yl)thioéthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridazin-4-yl) thioethyl] piperidine acid 3-carboxylic acid

Acide (3R4R)A-[3-(R.S)-hydroxy-3-(6-mé±oxyqumolm-4-yl)propyl]-1 -[3-(pyridazm-4~ 2 o yl)thiopropyl]pipéridine-3-carboxylique(3R4R) -A- [3- (RS) -hydroxy-3- (6-methyl-4-yl) -propyl] -1- [3- (pyridaz-4-yl) thiopropyl] -piperidine-3-acid (3R4R) carboxylic

Acide (3R4R) A-[3-(RS)-bydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-phényl-prop-2-ynyl]-pipéridine-3-carboxylique(3R4R) A- [3- (RS) -Bydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenyl-prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-CR_S)-hydroxy-3-(6-méthoxyquinoLin-4-yl)propyl]-1 -[3-(2-fluoro-phényl)-prop-2-\'nyl]-pipéridine-3-carboxylique 2 5 Acide (3R4R)-4-[3-(RS)-hydroxy-3-(6-méthûxyquinolin-4-yl)propyl]-1 -[3-(4-fluoro-pbényl)-prop-2-ynyl] -pipéridine-3 -carboxylique(3R, 4R) -4- [3-CR-S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluoro-phenyl) -prop-2-yl] acid nyl] -piperidine-3-carboxylic acid (3R4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluoro) -2- pbenyl) -prop-2-ynyl] -piperidine-3-carboxylic

Acide (3R4R)-4-[3-(RS)-hydrox>--3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-chloro-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R4R) -4- [3- (RS) -Hydrox-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-phenyl) -prop-2-ynyl) acid ] -piperidine-3-carboxylic acid

Acide (3R4R)-4-[3-(RS)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-chloro-2 0 phényl)-prop-2-ynyl]-pipéridine-3-carboxyhque(3R4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-phenyl) -prop-2-ynyl) acid ] -piperidine-3-carboxyhque

Acide (3R4R)-4-[3-(P_S)-hydroxy-3-(6-méthoxyquinolin-l-yl)propyl]-1 -[3-(4-chloro-phényl)-prop-2-\'nyl]-pipéridine-3-carboxylique(3R4R) -4- [3- (P_S) -hydroxy-3- (6-methoxyquinolin-1-yl) propyl] -1 - [3- (4-chloro-phenyl) -prop-2-ylyl) -acid ] -piperidine-3-carboxylic acid

Acide (3R4R)-4-[3-(R.S)-hydroxy'-3-(6-méthoxyquinolin-l-yl)propyl]-1 -[3-(2-méthyl-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique 2 Ξ Acide (3R,4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl- phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R4R) -4- [3- (RS) -Hydroxy-3- (6-methoxyquinolin-1-yl) propyl] -1- [3- (2-methyl-phenyl) -prop-2-ynyl] acid -Piperidine-3-carboxylic acid 2 Ξ (3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl) - phenyl) -prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R4R)-4-[3-(RS)-hydroxy-3-(6-méthoxyquinolm-i-yl)propyl]-1 -[3-(4-méthvl-phényl)-prop-2-yny 1 ]-pipéridine- 3 -carboxylique(3R4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinol-1-yl) propyl] -1- [3- (4-methyl-phenyl) -prop-2-yn] -acid 1] -piperidine-3-carboxylic

Acide (3R4R)-4-[3-(RS)-hydroxy-3-(6-méthoxyquinolin-4-\i)propyl]-1 - [3-( 2- 3 c trifluorométhyl-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethyl-phenyl) -prop-2- acid ynyl] -piperidine-3-carboxylic acid

Acide (3R4R)-4-[3-(RS)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3 - tnfluorométhyl-phén\i)-prop-2-\nyl]-pipéridine-3-carboxybque(3R4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-tnfluoromethyl-phenyl) -prop-2-yl] acid nyl] -piperidine-3-carboxybque

Acide (3R,4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxvquinolin-4-yl)propyl]-1 -[3-(4- trifluorométhyl-phényl )-prop-2->Oyl]-pipéridine-3-carboxylique ’ 3 : Acide (3R,4R)-4-[3-(RS)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-méthoxy- \ phényl)-prop-2-ynyl]-pipéridine-3-carboxylique 120 22 39(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxvquinolin-4-yl) propyl] -1- [3- (4-trifluoromethyl-phenyl) -prop-2-) - acid Oyl] -piperidine-3-carboxylic acid 3 (3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- Methoxyphenyl) -prop-2-ynyl] -piperidine-3-carboxylic acid 120 22 39

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthoxy- phényl)-prop-2-ynyl]-pipéridme-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-methoxyphenyl) prop-2 -acid) ynyl] -pipéridme-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl ;propyl]-l-[3-(4-méthoxy- phényl)-prop-2-ynylJ-pipéridine-3-carboxyiique 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl!propyl]-1 -[3-(3,4-difluoro-phényl)-prop-2-ynyl]-pipéridine-3-caiboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenyl) prop-2) -acid -Nyl-Piperidine-3-carboxylic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl] propyl] -1- [3- , 4-difluoro-phenyl) -prop-2-ynyl] -piperidine-3-caiboxylique

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yI ipropyl]-l -[3-(2,4-difluoro-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique . Acide (3R,4R)4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-y})propyl]-l-[3-(3,4-dichloro-10 phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-difluoro-phenyl) propyl) -acrylic acid; 2-ynyl] -piperidine-3-carboxylic acid (3R, 4R) 4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4-dichloro-phenyl) -prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)^-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yI)propyl]-1 -[3-(23-dichloro-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) - [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (23-dichloro-phenyl) prop-2 -acid] acid ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yi)propyl]-1 -[3-(2 A-dichloro-phényl)-prop-2-ynyl]-pipéridme-3-carboxylique 15 Acide (3R,4R)-4~l3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,4,6-trichloro-phényl)-prop-2-ynyl]-pipéridiiie-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2A-dichlorophenyl) propyl) -acrylic acid; 2-ynyl] -piperidin-3-carboxylic acid (3R, 4R) -4-3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- ( 2,4,6-trichloro-phenyl) -prop-2-ynyl] -pipéridiiie-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3,S-dichlorophényi)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3, 5-dichlorophenyl) prop-2-acid) ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)^4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-chloro3-2 o fluorœphényi)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) 4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro) -2-fluoro-p-phenyl) -prop acid -2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méîhoxyquinolin-4-yl)propyl]-1 -[3 -(3-chloro-4-fluoro-phényl)-prop-2-ynyl]-pipéridine-3-carboxyiique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3 - (3-chloro-4-fluoro-phenyl) acid -prop-2-ynyl] -piperidine-3-carboxylic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yi)propylj-1 -[3-(2-chloro-4-fîuoro-phényl)-prop-2-ynyl]-pipéridine-3-caiboxyiique 2 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4 -yl)propyl]-l -[3-(3-chloro-5- fluoro-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4-fluoro-phenyl) - acid) prop-2-ynyl] -piperidine-3-caiboxyic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (3-Chloro-5-fluoro-phenyl) -prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R4R)-4-[3-(R,S)-hydroxy-3-(6-méihoxyquinolin-4-yl)propyl]-1 -[3-(4-chloro~2-fluoro-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (4-chloro-2-fluoro-phenyl) -prop acid -2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-fluoro-4- 3 0 méthyl-phényl)-prop-2-ynyl]-pipéridme-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-fluoro-4-methyl) -acrylic acid; phenyl) -prop-2-ynyl] -pipéridme-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-chloro-3- trifluorométhyl-phényl)-prop-2-ynyl]-pipéridine-3-carboxyhque(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3-trifluoromethyl-phenyl) acid) -prop-2-ynyl] -piperidine-3-carboxyhque

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-chloro-4- trifluorométhyl-phényl)-prop-2-ynyl]-pipéridine-3-carboxvlique 3 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-chloro-5- trifluorométhyl-phényl)-prop-2*\rnyl]-pipéridine-3*carboxyiique 40(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4-trifluoromethyl-phenyl) acid) 1-Prop-2-ynyl] -piperidine-3-carboxylic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 [3- (2-Chloro-5-trifluoromethyl-phenyl) -prop-2-yl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S>hydroxy-3-(6-méthoxyquinoIm-4-yl)propyl]-1 -[3-(5-chloro-2- méthoxy-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chloro-2-methoxy-phenyl) - prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R>4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3,5-bis- trifluorométhyl-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) 4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-bis-trifluoromethyl-phenyl) - acid) prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(KS)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-(3,5-diméthyl- phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (KS) -hydroxy-3- (6-methoxyquolin-4-yl) propyl] -1 - [3- (3,5-dimethylphenyl) prop-2 -acid] acid ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)^4-[3-(R,S)-hydroxy-3-(6-méthoxy7quinolin-4-yl)propyl]-1 -[3-(2.4-dichloro-6-méîhyl-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) 4- [3- (R, S) -hydroxy-3- (6-methoxy-7-quinolin-4-yl) propyl] -1- [3- (2,4-dichloro-6-methylphenyl) acid) -prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3RAR)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolirM-yl)propyl]-1 -[3-(5-chloro-thien-2-yl)-prop-2-ynyl]-pipéridine-3-carboxylique(3RAR) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-1-yl) propyl] -1 - [3- (5-chloro-thien-2-yl) -prop-2 -acid) ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-chloro-thien-2-yl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-thien-2-yl) acid) -prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R.4R)^i-[3-(R,S)-hydroxy^3-(6-méthoxyquinolin-4-y])propyl]-1 -[3-(5-méthyl-thien-2-yl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R4R) 1- [3- (R, S) -hydroxy) -3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-methyl-thien-2-yl) -acid ) -prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R.4R)^-[3-(R_S)-hydrox>'-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-méihyl-thien-2-yl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) 1- [3- (R) S -hydroxyl] -3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-thien-2-yl) - prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R4R)A-[3-(R.S)-hydroxy-3 (6-méthoxyquinolin-4-yl)propyl]-1 -[3-(thien-3-yl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R4R) -A- [3- (RS) -hydroxy-3 (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) -prop-2-ynyl] -piperidine-acid 3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin^l-yl)propyl]-1 -[3-( 1 -méthyl-pyrrol- 2- yl)-prop-2-\nyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-1-yl) propyl] -1 - [3- (1-methyl-pyrrol-2-yl) acid -prop-2- \ nyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-( 1 -méthyl-pyrrol- 3- yl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methyl-pyrrol-3-yl) prop) -2-ynyl] -piperidine-3-carboxylic acid

Acide (3R.4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-( 1J-thiazol-2-vl)-prop-2-\nyl ] -pipéridine-3 -carboxvlique(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1H-thiazol-2-yl) prop-2-acid) [Nyl] -piperidine-3-carboxy]

Acide (3RAR)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)pfopyl]-1 -[3-( 1,3-thiazol-4-yl)-prop-2-\Tiyl]-pipéridine-3-carboxylique(3RAR) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) pfopyl] -1- [3- (1,3-thiazol-4-yl) -prop-2 -acid) - \ Tiyl] -piperidine-3-carboxylic acid

Acide (3R4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(1.3-thiazol-5-\i)-prop-2-\n\l]-pipendine-3-carbox\iique(3R4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-5-i-prop-2-yl) propanic acid) \ n \ t] -pipendine-3-carbox \ liquefying

Acide (3R.4R)-4-[3-(R.S)-hydroxy-3-(6-méthox\quinolin-4-yl)propyl]-1 -[3-( 1 -méthyl-imidazol-2 -yl)-prop-2-ynyl] -pipéridine-3 -carboxvlique(3R4R) -4- [3- (RS) -hydroxy-3- (6-methoxylquinolin-4-yl) propyl] -1 - [3- (1-methyl-imidazol-2-yl) acid -prop-2-ynyl] -piperidine-3-carboxy

Acide (3RAR)-4-[3-(R-S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl-imidazol-4-yl )-prop-2-ynyl]-pipéridine-3-carboxylique(3RAR) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-methyl-imidazol-4-yl) prop-2 -acid) ynyl] -piperidine-3-carboxylic acid

Acide (3RAR)-4-[3-fR.S)-hydroxy-3-(6-méthoxvquinolin-4-yl)propyI]-1 -[3-(3-méthyl-p\Tazol-4-yl)-prop-2-\Tiyl]-pipéridine-3-carboxylique(3RAR) -4- [3- (3-Pr. S) -hydroxy-3- (6-methoxvquinolin-4-yl) propyl] -1- [3- (3-methyl-p-azol-4-yl) -acid) - prop-2 \ Tiyl] -piperidine-3-carboxylic acid

Acide (3RAR)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(oxazol-2-yl)-prop-2-ynyl]-pipéridine-3-carboxylique 120 2 2 41(3R-R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) -prop-2-ynyl] - acid piperidine-3-carboxylic acid 120 2 2 41

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(oxazol-4-yl)- prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-4-yl) prop-2 acid) ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-métboxyquinolin-4-yl)propyl]-1 -[3-(oxazol-5-yl> prop-2-ynyl]-pipéridine-3-caiboxylique 5 Acide (3R,4R)-4-[3-(R)S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyI3-1 -[3-(pyridin-2-yl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-metboxyquinolin-4-yl) propyl] -1- [3- (oxazol-5-yl) prop-2- acid [(R, 4 R) -4- [3- (R) S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridinyl) -2-yl) -piperidine-3-caiboxylic acid 2-yl) -prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)^4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(pyridin-3-yl)-prop-2-ynyl]-pipéridine-3-carboxylique . Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méÎho?iyquinolin-4-yl)propyl]-1 -[3-(pyridin-4-yl)-10 prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) 4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (pyridin-3-yl) prop-2) acid -ynyl] -piperidine-3-carboxylic acid. (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxy-iyquinolin-4-yl) propyl] -1 - [3- (pyridin-4-yl) -10 -acidic acid prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(RS)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-2-yl)prop-2-ynyl]-pipéridine-3-caiboxylique(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) prop-2-ynyl] acid -piperidin-3-caiboxylique

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl3-1 -[3-(pyrimidin-4-yl)prop-2-ynyl]“pipéridine-3-caiboxylique 15 Acide (3R,4R)-4-[3-(R,S}-hydroxy-3-(6-méthoxyquinolm-4-yi)propyl]-1 -[3-ipyrimidin-5-yl) prop-2-ynyl]-pipéridme-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (pyrimidin-4-yl) prop-2-ynyl) acid ] Piperidine-3-caiboxylic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [3-ipyrimidin-5] -yl) prop-2-ynyl] -piperidin-3-carboxylic

Acide (3R4R)-4-[3-(R,S)-hydioxy-3-(6-méthoxyquinolin-4-yl)propyI]-1 -[3-(pyrazin-2-yl)-prop-2-ynyl]-pipéridine-3-carbo?cylique(3R4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) -prop-2-ynyl) acid ] -piperidine-3-carbo? cylique

Acide (3R,4R)-4-[3-(R,S)-bydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridazm-3-yl)-20 prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -bydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridaz-3-yl) -propyl) -propionic acid; 2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridazin-4-yl)prop-2-ynyl]-pipéridiue-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4-yl) prop-2- acid) ynyl] -pipéridiue-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthox)'quinoUn-4-yl)propyl]-1 -[3-phénylpropèn-2yl]pipéridine-3-carboxylique 2 5 Acide (3R,4R)A-[3-f{tS)-hydroxy-3-(6-méthoxyqumolin-4-yl)propy· r i -[4-phénylbutèn-3- yl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxy) quinolin-4-yl) propyl] -1- [3-phenylpropen-2-yl] piperidine-3- acid carboxylic acid (3R, 4R) A- [3-tert -hydroxy-3- (6-methoxyquolin-4-yl) propyl] - [4-phenylbuten-3-yl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-phénylbutyl]pipéridine-3 -carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4-phenylbutyl] piperidine-3-carboxylic acid

Acide (3R>4R)-4-[3-(R.S)-fluoro-3-(6-méthoxyquinoEn-4-yl)propyl3-1 -[3-(2- 3 o fluorophényl)propyl]pipéridine-3-carboxylique(3R-R) -4- [3- (R) -Fluoro-3- (6-methoxyquinin-4-yl) propyl] -1 - [3- (2-fluorophenyl) propyl] piperidine-3-carboxylic acid

Acide (3R4R)-4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyî]-1 -[4-(2-fluorophényl)butyl]pipéridine-3-carboxylique(3R4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-fluorophenyl) butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-fluorophényl)propyl]pipéridine-3-carboxylique 3 5 Acide (3R,4R)-4-[3-(R.S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[4-(3-fluorophényl)butyl]pipéridine-3-carboxylique 4 120 2 2 42(3R, 4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) propyl] piperidine-3-carboxylic acid 3 (3R, 4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [4- (3-fluorophenyl) butyl] piperidine-3-carboxylic acid 4 120 2 2 42

Acide (3R4R)^4-[3-(R,S)-fluoro-3-(6-méthoxyquinoIin-4-yl)propyl]-1 - [3-(4- fluorophényl)propyl]pipéridine-3-carboxylique(3R4R) 4- [3- (R, S) -Fluoro-3- (6-methoxyquinin-4-yl) propyl] -1- [3- (4-fluorophenyl) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(4- fluorophényl)butyl]pipéridine-3-carboxylique 5 Acide (3R4R)-4-[3-(R,S)-fluor(>-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2.3- difluorophényl)propyl]pipéridine-3-carboxyliqueAcide (3R.4R)-4-[3-(R,S)-fluoro-3-(6-Tnéthoxyquinolin-4-yl)propyl]-1 -[4-12,3-difluorophényl)butyl]pipéridme-3-caiboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-fluorophenyl) butyl] piperidine-3- acid carboxylic acid (3R4R) -4- [3- (R, S) -fluor (> - 3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl) propyl] piperidine- 3-Carboxylic Acid (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4-12,3-difluorophenyl) butyl] piperidin -3-caiboxylique

Acide (3R4R)^4-[3-(R.S)-fluoro-3-(6-méthoxyquinolin^}-yl)propyl]-1 -[3-(2,6-ï o difluorophényl)propyl]pipéridine-3-carboxylique(3R4R) 4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-1-yl) propyl] -1- [3- (2,6-difluorophenyl) propyl] piperidine-3- acid carboxylic

Acide (3R,4R)-4-[3-fR.S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[4-(2,6-difluorophényl)butyl]pipéridine-3-carboxybque(3R, 4R) -4- [3-fluoro] -fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [4- (2,6-difluorophenyl) butyl] piperidine-3-acid -carboxybque

Acide (3R,4R)-4-[3-(R.S)-fluoro-3-(6-rnéihoxx'quinolin-4-yl)propyl]-1 -[3-(2-chlorophényl)propy]]pipéridine-3-carboxylique : : Acide f3R,4R)-4-[3-(R5)-fluoro-3-(6-me±oxYquinolm-l-yl)propyl]-i-[4-(2-chlorophényl)butyl]pipéridine-3-carboxx'lique(3R, 4R) -4- [3- (RS) -Fluoro-3- (6-fluorochenquinolin-4-yl) propyl] -1- [3- (2-chlorophenyl) propyl] piperidine-3-acid -carboxylic acid: f3R, 4R) -4- [3- (R5) -Fluoro-3- (6-methyl-i-yl) quinolin-1-yl) propyl] - [4- (2-chlorophenyl) butyl] piperidine acid; -3-carboxx'lique

Acide (3R4R)-4-[3-fRS)-iluoro-3-(6-méîhoxyquinolin-4-yl)propyl]-l -[3-(3-chlorophényl)propyl]pipéridine-3-carboxylique(3R4R) -4- [3-fRS) -Lluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenyl) propyl] piperidine-3-carboxylic acid

Acide (3R.4R)-4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-]-[4-(3- 2 o chJorophényl)butyl]pipéridine-3-carboxylique(3R4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -] - [4- (3-chlorophenyl) butyl] piperidine-3- acid carboxylic

Acide (3R4R)-4-[3-(R.S)-fluoro-3-(6-méihoxyquinolin-4-yl)propyl]-l-[3-(4-chlorophényl)propy]]pipéridine-3-carboxylique(3R4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenyl) propyl] piperidine-3-carboxylic acid

Acide (3R.4R)^-[3-{R.S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(4-ch]orophényl)butyl]pipéridine-3-caiboxvlique 2 5 Acide (3R4R)-4-[3-(R.S)-fluoro-3-(6-méihoxvquinolin-4-yl)propyl]-l-[2 ,2,3-dichlorophén\-l)prop>i]pipéridine-3-carboxylique(3R4R) 1- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-chlorophenyl) butyl] piperidine-3-caiboxylic acid (3R4R) -4- [3- (RS) -Fluoro-3- (6-methoxivinolin-4-yl) propyl] -1- [2,2,3-dichlorophen-1-prop] -acid] piperidine-3-carboxylic acid

Acide (3R4R)-4-[3-(R.S)-iluoro-3-(6-méthoxyquinolin-4-yl)propyl]-]-[4-(2.3-dichlorophénvl )but> ljpipéridine-3-carbo\> bque(3R4R) -4- [3- (RS) -Lluoro-3- (6-methoxyquinolin-4-yl) propyl] -] - [4- (2,3-dichlorophenyl) butane] piperidine-3-carbohydrate acid

Acide (3R4R)-4-[3-(’RS)-fluoro-3-(6-méthoxyquinolin-4-\l)propyl]-l-[3-(2.6- 5 o dichlorophényl)propyl]pipéridme-3-carboxvlique(3R4R) -4- [3 - ('RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-dichlorophenyl) propyl] piperidin-3- acid carboxylic

Acide (3R4R)-4-[3-(R.S )-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(2.6-dichlorophényl)buty]jpipéridine-3-carboxylique(3R4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-dichlorophenyl) butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R.S)-fluoro3-(6-méthoxyquinolin-4-yl)propyl]-1-(3-(2-méthy]phény])propYl]pipéridine‘-3-carboxylique 5 5 Acide ( 3R.4R>4-[3-(R.S)-fluoro-3-{6-méthoxyquinolin-4-yl)propyl]-l -[4-(2-méthylphénvl )butyl ]pi péridine-3-carboxvhque 120 2 2 43(3R, 4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (2-methyl) phenyl] propyl] piperidine-3-acid carboxylic acid 5 (3R.4R) 4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-methylphenyl) butyl] peridoridin-3 -carboxvhque 120 2 2 43

Acide (3R,4R)-4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1-(5-(2- méthylphényl)pentyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (5- (2-methylphenyl) pentyl] piperidine-3-carboxylic acid

Acide (3R4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(3-(3- méthylphényl)propyl]pipéridine-3-carboxylique 5 Acide (3R,4R)-4-(3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(4-(3-méthylphényl)butyl]pipéridine-3-caiboxylique(3R4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (3-methylphenyl) propyl] piperidine-3-carboxylic acid 5 (3R, 4R) -4- (3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (4- (3-methylphenyl) butyl] piperidine-3- acid caiboxylique

Acide (3R,4R)-4-(3-(R,S)-fluoro-3-(6-mé±oxyquinolin-4-yl)propyl]- i -(3-(4- méthylphényl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- (3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (4-methylphenyl) propyl] piperidine 3-carboxylic acid

Acide (3R4R)-4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(4- 10 méthylphényl)butyl]pipéridme-3-carboxylique(3R4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-methylphenyl) butyl] piperidin-3-carboxylic acid

Acide (3R,4R)-4-(3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l -(3-(2-méthoxyphényl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- (3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (2-methoxyphenyl) propyl] piperidine-3- acid carboxylic

Acide (3R4R)-4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(4-(2-méthoxyphényl)butyî]pipéridine-3-carboxylique 15 Acide (3R4R)-4-[3-(RS}-fluoro~3-(6-méthoxyquinolm-4-yl)prûpyl]-l-[3-(3-méthoxyphényl)propyl]pipéridine-3-caiboxyliqueAcide (3R4R)-4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(4-(3-méthoxyphényl)butyl]pipéridine-3-carboxylique(3R4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (4- (2-methoxyphenyl) butyl] piperidine-3-carboxylic acid acid ( 3R4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (3-methoxyphenyl) propyl] piperidine-3-caiboxylicAcid (3R4R) -4 [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (4- (3-methoxyphenyl) butyl] piperidine-3-carboxylic acid

Acide (3 R,4R)-4-(3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1-(3-(4- 2 o méthoxyphényl)propyl]pipéridine-3-carboxylique(3 R, 4 R) -4- (3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (4-methoxyphenyl) propyl] piperidine acid -3-carboxylic acid

Acide (3R4R)-4-(3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(4-(4-méihoxyphényl)butyl]pipéridine-3-carboxyl i que(3R4R) -4- (3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (4- (4-methoxyphenyl) butyl] piperidine-3-carboxylic acid than

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l -(3-(2-trifluorométhylphényl)propyl]pipéridine-3-carboxylique 2 5 Acide (3R,4R)-4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(4-(2- trifluorométhylphényl)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (2-trifluoromethylphenyl) propyl] piperidine-3- acid carboxylic acid (3R, 4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (4- (2-trifluoromethylphenyl) butyl] piperidine-3 carboxylic

Acide (3R4R)-4-(3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(3-(3- trifluorométhylphényl)propyl]pipéridine-3-carboxylique(3R4R) -4- (3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (3-trifluoromethylphenyl) propyl] piperidine-3-carboxylic acid

Acide (3R4R)-4-[3-(R.S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(4-(3- 3 o trifluorométhylphényl)butyl]pipéridine-3-carboxylique(3R4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (4- (3-trifluoromethylphenyl) butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-(3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(3-(4- trifluorométhylphényl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- (3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (4-trifluoromethylphenyl) propyl] piperidine-3- acid carboxylic

Acide (3R4R)-4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(4-(4- trifluorométhylphényl)butyl]pipéridine-3-carboxylique 3 5 Acide (3R4R)-4-[3-(RS)-fluorO'3-(6-méthoxyquinolin -4-yl)propyl]-1 -[3-phénylthio- éthyl]pipéridine-3-carboxylique 120 2 2 44(3R4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (4- (4-trifluoromethylphenyl) butyl] piperidine-3-carboxylic acid Acid (3R4R) -4- [3- (RS) -FluoroO3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylthioethyl] piperidine-3-carboxylic acid 120 2 2

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolmA-yl)propyl]-1 -[3-phénylthio- propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-yl) propyl] -1- [3-phenylthiopropyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R.S)-fluoro-3-f6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2- fluorophénylthio)propyl]pipéridine-3-carboxylique 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[3-(3-fluorophénylthio)propyl]pipéridine-3-carboxyliqueAcide (3R_4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[2-(2-fluorophénylthio)élhyl]pipéridine-3-carboxyliqueAcide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin^-yl)propyl]-1 -[2-(4- 1 o fluorophénylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (RS) -Fluoro-3-yl-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenylthio) propyl] piperidine-3-carboxylic acid acid (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenylthio) propyl] piperidine-3 Carboxylic acidAct (3R_4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [2- (2-fluorophenylthio) ethyl] piperidine-3-carboxylic acid (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquolin-1-yl) propyl] -1- [2- (4-fluoro-phenylthio) ethyl] piperidine-3 carboxylic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 - [3-(4-fluorophénylthio)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenylthio) propyl] piperidine-3- acid carboxylic

Acide (3R.4R)-4-[3-(KS)-fluoro-3-(6-méthoxyquinolmA-yl)propy:]-1 -[2-(2.3-difluorophénylthio)éthyl]pipéridine-3-caiboxylique : Acide (3R,4R)-4-[3-(R.S)-fluoro-3-(6-méthoxyquinolin^-yl)propyl]-1 -[3-(2.3- difluorophénylthio)propyl]piperidme-3-C3rboxylique(3R.4R) -4- [3- (KS) -Fluoro-3- (6-methoxyquinol-4-yl) propyl]] - 1 - [2- (2,3-difluorophenylthio) ethyl] piperidine-3-caiboxylic acid: Acid (3R, 4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-1-yl) propyl] -1- [3- (2,3-difluorophenylthio) propyl] piperidin-3-carboxylic acid

Acide (3R.4R)- 4-[3-(R_S)-fluoro-3-(6-méthoxyquinoLin-4-yl)propyl]-1 -(2-(2.6- difluorophénylthio)éthyl]pipéridine-3-carboxylique(3R.4R) - 4- [3- (R-S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (2- (2,6-difluorophenylthio) ethyl] piperidine-3-carboxylic acid

Acide (3R.4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl'ipropyl]-1 -[3 -(2,6- 2 o difluorophénylthio)propyl]pipéridine-3-carboxylique(3R4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl-propyl] -1 - [3- (2,6-difluorophenylthio) propyl] acid piperidine-3-carboxylic acid

Acide (3R.4R)^l-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yi)prop> 1]-1-(2-(2-chlorophénvlthio)éthyl]pipéridine-3-carboxylique(3R, 4 R) 1- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) prop-1] -1- (2- (2-chlorophenylthio) ethyl] piperidine acid; 3-carboxylic acid

Acide (3R.4R)-4-[3-(R-S)-fluoro-3-f6-méthoxyquinolin-4-yl ipropyl]-1 -(3-(2-chlorophénylthio)propyl]pipéridine-3-carboxylique 2 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(2-(3-chlorophénylthio)éthyl]pipéridine-3-carboxyliqueAcide (3R.4R)^4-[3-(R.S)-fluoro-3-( 6-mé±oxyquinolin-4-yl)propyl]-l-(3-(3-chlorophénylthio)propyl]pipéridine-3-carboxyliqueAcide (3R.4R)^[3-(R.S)-fluoro-3-(6-méthoxyquinohn-4-\ 1 ipropyl]-1 -(2-(4- ξ o chlorophénylthio)éthyl]pipéridine-3-carboxylique(3R4R) -4- [3- (RS) -Fluoro-3-f-methoxyquinolin-4-yl] propyl] -1- (3- (2-chlorophenylthio) propyl] piperidine-3-carboxylic acid Acid (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (2- (3-chlorophenylthio) ethyl] piperidine-3-carboxylic acid (3R4R) 4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (3-chlorophenylthio) propyl] piperidine-3-carboxylic acid (3R4R) 3- [3- (RS) -Fluoro-3- (6-methoxyquinino-4-propyl) -1- (2- (4-chlorophenylthio) ethyl] piperidine-3-carboxylic acid

Acide (3R.4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl ipropyl]-1 -[3-(4-chlorophénylthio)propyl]pipéridine-3-carboxylique(3R4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenylthio) propyl] piperidine-3-carboxylic acid

Acide (3R.4R)-4-(3-(R,S)-fluoro-3-(6-métlioxyquinolin-4-yl ipropyl]-1 -(2-(2.3- dichlorophénylîhio)éthyl]pipéridine-3-carboxylique * Ξ 5 Acide (3RAR)-4-[3-(KS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2.3- dichlorophénylthio)propyl]pipéndine-3-carboxvlique 120 22 45(3R4R) -4- (3- (R, S) -Fluoro-3- (6-methylquinolin-4-yl) propyl] -1- (2- (2,3-dichlorophenylthio) ethyl] piperidine-3-carboxylic acid * Ξ 5 (3RAR) -4- [3- (KS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichlorophenylthio) propyl] pipetin-3-carboxylic acid 120 22 45

Acide (3R,4R)-4-[3-(R,S)-fluoro3-(6-méthoxyqumolin-4-yl)propyl]-1 -[2-(2,6- dichlorophénylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1 - [2- (2,6-dichlorophenylthio) ethyl] piperidine-3- acid carboxylic

Acide (3R,4R)-4-f3-(RtS')-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l -(3-(2,6- dichlorophényîthio)propyl]pipéridine-3-carboxylique 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolinj4-yl)propyl]-1 -(2-(2-méthylphénylthio)éthyl]pipéridme-3-carboxyliqueAcide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-méthylphénylthio)propyl]pipéridine-3-carboxyliqueAcide (3R,4R)-4-[3-(R,S)-fluora-3-(6-niéthoxyquinolin-4-yl)propyl]-1 -[2-(3 - 1 o méthylphénylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (RtS ') - fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (2,6-dichlorophenylthio) propyl] piperidine-3- acid carboxylic acid (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (2- (2-methylphenylthio) ethyl] piperidin-3- carboxylic acid (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenylthio) propyl] piperidine-3- carboxylic acid (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-1-methylphenylthio) ethyl] piperidine- 3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluora-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3- méthylphénylthio)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenylthio) propyl] piperidine-3- acid carboxylic

Acide (3R,4R)-4-[3-(R,S)-fluor(>-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(4- méthylphénylthio)éthyl]pipéridine-3-caiboxyIique 15 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6~méthoxyquinoün-4-yl)propyl]' 1 -[3-(4- méthylphénylthio)propyi]pipéridine-3-carboxyliqueAcide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(2-(2-trifluorométhylhénylthio)éthyl]pipéridine-3-carboxyliqueAcide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méihoxyquinolin-4-yl)propyl]-l -[3-(2- 2 O triflurométhylphénylthio)propyl]pipéridine-3-caiboxylique(3R, 4R) -4- [3- (R, S) -Fluor (> - 3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methylphenylthio) ethyl] piperidine acid 3-Caiboxylic acid (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquino-4-yl) propyl] -1- [3- (4-methylphenylthio) propyl] Piperidine-3-carboxylic acid (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (2- (2-trifluoromethyl-enylthio) ethyl] piperidine-3-carboxylic acid (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2- [2-trifluromethylphenylthio)) propyl] piperidin-3-caiboxylique

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3- trifluorométhylphénylthio)éllwl]pipéridine-3-carboxyîique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethylphenylthio) propyl] piperidine-3- acid carboxylic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6~méthoxyquinolin-4-yl)propyl]-1 -[3-(3- triflurométhylphényW!!o)propyl]pipéridine-3-caîboxylique 2 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l -[2-(4- trifluorométhylphénylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluromethylphenyl) o) propyl] piperidine acid -3-carboxylic acid (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-trifluoromethylphenylthio)) ethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(RS)-fluoro-3-(6-méthoxyquinoiin^-yl)propyl]-l -[3-(4- triflurométhyiphénylthio)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluromethylphenylthio) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin4-yl)propyl]-1 -[2-(2- 3 o méthoxyphénylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (2-methoxyphenylthio) ethyl] piperidine-3- acid carboxylic

Acide (3K4R)-4-[3-(R,S)-fluorœ3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-(2- méthoxyphénylthio)propyl]pipéridine-3-carix)xylique(3K4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (2-methoxyphenylthio) propyl] piperidine-3-carix) xyl acid

Acide (3R,4R)-4-[3-(KS)-fluoro-3-(6-méthoxyquinoEn-4-yl)propyl]-l -[2-(3- méthoxyphénylthio)éthyî]pipéridine-3-carbox\’lique 3 5 Acide (3R,4R)j4-[3-(R.S)-fluoro-3-(6-méihoxyquinolin-4-yl)propyl]-1 - [3-(3- méthoxyphénylthio)propyl]pipéridine-3-carboxylique 46(3R, 4R) -4- [3- (KS) -Fluoro-3- (6-methoxyquinin-4-yl) propyl] -1- [2- (3-methoxyphenylthio) ethyl] piperidine-3-carbox] acid (3R, 4R) 4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenylthio) propyl] piperidine-3-acid -carboxylic 46

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(4-méthoxyphénylthio)éthyl]pipéridine-3-carboxylique a <n'. 1 c\ n . · · - · méthoxyphénylthio)propyl]pipéridme-3-carboxy]ique5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l - [cyclopropylmé±yl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methoxyphenylthio) ethyl] piperidine-3- acid carboxylic acid a <n '. 1 c \ n. · (Methoxyphenylthio) propyl] piperidin-3-carboxy] acid (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 [cyclopropylmethyl] piperidine-3-carboxylic acid

Acide (3R.4R)-4-[3-CR,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l -[2- (cyclopropyl)éthyl]pipéridine-3-carboxylique(3R4R) -4- [3-CR, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopropyl) ethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-{R,S)-fluoro3-(6-méthoxyquinolin-4-yl)propyl]-1 - 1 o [cyclobuÎylméthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1-o [cyclobutylmethyl] piperidine-3-carboxylic acid

Acide (3R.4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2- (cyclobutyl)éthyl]pipéridine-3-carboxylique(3-4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclobutyl) ethyl] piperidine-3-carboxylic acid

Acide (3R_4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 - [cyclopentylméthyl]pipéridine-3-caiboxylique 15 Acide (3R.4R)-4-[3-(R.S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl j-1 -[2- (cyclopentyl)éÎhyljpipéridme-3-carboxyliqueAcide (3R.4R)-4-[3-(R_S)-fluoro-3-(6-méthoxyquinolin-4-\-l)propyl]-l -[cyclohexylméthyl]pipéridine-3 -carboxylique(3R- [4R] -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [cyclopentylmethyl] piperidine-3-caiboxylic acid Acid (3R.4R) - 4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentyl) hexyl] piperidin-3-carboxylic acidAcid (3R.4R) -4- [3- ( R-S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [cyclohexylmethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R.S)-fluoro-3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[2- 2 0 (cyclohexyl)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (RS) -Fluoro-3- (6-methyloxy-4-yl) propyl] -1 - [2- (cyclohexyl) ethyl] piperidine-3- acid carboxylic

Acide (3R,4R)-4-[3-(R.S)-fluoro3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2- (cyclopropylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopropylthio) ethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-\l)propyl]-1 -[3- (cyclopropylthio)propyl]pipéridine-3-carboxylique 2 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yllpropyl]-1 -[2- (cyclobutylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopropylthio) propyl] piperidine-3-carboxylic acid (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyqumolin-4-ylpropyl) -1- [2- (cyclobutylthio) ethyl] piperidine-3-carboxylic acid

Acide (3R,4R)^4-[3-(R.S)-fluoro-3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[3- (cyclobutylthiopropyl]pipéridine-3-carboxylique(3R, 4R) 4- [3- (RS) -Fluoro-3- (6-methyloxy-4-yl) propyl] -1 - [3- (cyclobutylthiopropyl) piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-( R.S )-fluoro-3-(6-méthox\quinolin-4-yl)propyl]-1 -[2- 3 c (cyclopentylthio)é±yl]pipéridine-3-carboxvlique(3R, 4R) -4- [3- (RS) -Fluoro-3- (6-methoxylquinolin-4-yl) propyl] -1- [2- [3 (cyclopentylthio) ethyl] piperidine] acid 3-carboxylic acid

Acide (3R,4R)-4-[3-fR-S)-fluoro-3-(6-méthoxyquinolin-4-yl ipropyl]-1 -[3-(cyclopentylthio)propyl]pipénd>ne-3-carboxylique , Acide (3R,4R)-4-[3-(R.S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2- » icyclohexylthio)éthyl]pipéridine-3-carboxylique 3 3 Acide (3R.4R)-4-[3-(R.S)-fluoro-3-(6-méthoxyquinolin-4-yl ipropyl ]-1 -[3- x {cyclohexylihio)propyl]pipéridine-3-caiboxylique 120 2 2 47(3R, 4R) -4- [3-flu-S) -fluoro-3- (6-methoxyquinolin-4-ylpropyl] -1- [3- (cyclopentylthio) propyl] pipernd-ne-3-carboxylic acid, (3R, 4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (2-icyclohexylthio) ethyl] piperidine-3-carboxylic acid 3 acid (3R, 4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-x (cyclohexylthio) propyl] piperidine-3-caiboxylic 120 2 2 47

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-méthylthioéthyl]pipéridine-3-carbox}'lique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-methylthioethyl] piperidine-3-carboxylic acid

Acide (3K4R)-4-[3-(R,S)-fluoro-3-(6-méthox}-quinolin-4-yl)propyl]'l -[3-méthylîhiopropyl]pipéridine-3-carboxylique 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinoliii-4-yl)propyl]' 1 -[2- éÙiyithioéthyl]pipéridine-3-carboxylique(3K4R) -4- [3- (R, S) -Fluoro-3- (6-methox) -quinolin-4-yl) -propyl] -1- [3-methyl-i-propyl] -piperidine-3-carboxylic acid acid ( 3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-ethylidioethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]'l-[3-éthylthiopropyl]pipéridine-3'Carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-ethylthiopropyl] piperidine-3'-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(n-10 propylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (n-propylthio) ethyl] piperidine-3 acid carboxylic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-{6-inéthoxyquinolm-4-yl)propyl]-l-[3-(n-propylthio)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (n-propylthio) propyl] piperidine-3- acid carboxylic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]- l-[2-(n-butylthio)éthyl]pipéridine-3-carboxyIique 15 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(n-butylthio)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [2- (n-butylthio) ethyl] piperidine-3- acid Carboxylic acid (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (n-butylthio) propyl] piperidine- 3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)prcpyl]-l -[3-(thien-2-yl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) propyl] piperidine acid 3-carboxylic acid

Acide (3R,4R}-4-[3-(R,S)-fluoro-3-(6-méthoxyquixiolin-4-yl)propyl]-1 -[4-(thien-2-20 yl)butyl]pipàidine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquixiolin-4-yl) propyl] -1- [4- (thien-2-yl) butyl] piperidine acid -3-carboxylic acid

Acide (3R,4R)-4~[3-(R,S)-fluoro-3-(6-méihoxyquinolin-4~yl)propyl]-1 -[3-(thien-2-yI)thiopropyl]pipéridine-3-caiboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) thiopropyl] piperidine- 3-caiboxylique

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méÜioxyqumolm-4-yl)propyl]-l-[3-(5-chloro-thien-2·yî)propyî]pipéridine-3-caihoxyHque 25 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(5-chloro-ihien-2·yl)butyI]pipéridine-3-caiboxyIique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methyloxymolm-4-yl) propyl] -1- [3- (5-chloro-thien-2-yl) acid) propylpiperidin-3-chlorophenic Acid (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (5- chloro-2 · ihien-yl) butyI] piperidin-3-caiboxyIique

Acide (3R4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[2-(5-chloro-thien-2·yl)thioéthyl]pipéridine-3-carboxylique(3R4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [2- (5-chloro-thien-2-yl) thioethyl] acid piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin4-yl)piOpyl]-l-[3-(5-chloro-thien-230 yl)thiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) p-pyl] -1- [3- (5-chloro-thien-230-yl) thiopropyl] piperidine acid -3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-chloro-thien-2yl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-thien-2-yl) propyl] acid piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-iluoro-3-(6-niélhoxyquinolin-4-yl)propyl]-1 -[4-(3-chloro-thien-2yl)butyl]pipéridine-3-caiboxylique 3 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[2-(3-chloro-thien-2 yl)thioéthyl]pipéridine-3-carboxylique 120 2 2 48(3R, 4R) -4- [3- (R, S) -Lluoro-3- (6-niethyloxyquinolin-4-yl) propyl] -1- [4- (3-chloro-thien-2-yl) butyl] acid piperidine-3-caiboxylic acid (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [2- (3-chloro) -thien-2 yl) thioethyl] piperidine-3-carboxylic acid 120 2 2 48

Acide (3R,4R)^4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)prOpyl]-l -[3-(3-chloro-thien-2-yl)tbiopropyl]pipéridine-3-caiboxylique(3R, 4R) 4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-thien-2-yl) acid) tbiopropyl] piperidin-3-caiboxylique

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthox\'quinolin-4-yl)propyl]-l-[3-(5-méthyl -thien-2-vi ;propyi]pipendine-j-carboxylique 5 Acide (3R,4R)^[3-(R3)-fluorcH3-(6-méthoxyquinolin-4-yl)piOpyl]-1 -[4-(5-méthyl -thien-2-yl)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxinolin-4-yl) propyl] -1- [3- (5-methylthien-2) - acid Propyl (piperine) -dicarboxylic acid (3R, 4R) [3- (R3) -fluorcH3- (6-methoxyquinolin-4-yl) piOpyl] -1- [4- (5-methyl-thien) -2-yl) butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthox\'quinolin-4-yl)propyl]-1 -[2-(5-méthyl -thien-2-yl)thioé±yl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (5-methylthien-2) - acid yl) thioé ± yl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(RS)-fluoro-3-(6-méthox}'qumoün-4-yl)propyl]-1 -[3-(5-méthyl -thien-2-10 yl)thiopropyl]pipéridme-3-carboxylique(3R, 4R) -4- [3- (RS) -Fluoro-3- (6-methoxymethyl-4-yl) propyl] -1 - [3- (5-methylthien-2-10) - acid yl) thiopropyl] pipéridme-3-carboxylic acid

Acide (3R_4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl -thien-2-yl)propyl]pipéridine-3-carboxylique(3R_4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylthien-2-yl) propyl] acid piperidine-3-carboxylic acid

Acide (3R.4R)-4-[3-(KS)-fluoro-3-(6-méthoxyqujLnoLin-4-yl)propyl]-l -[4-(3-méthyl -xhien-2-yl)butyl]pipéridine-3-carboxylique 15 Acide (3R,4R)-4-[3-(R.S)-fluoro-3-(6-rriéthoxyquinolin-4-yl)propyl]-1 -[2-(3-méthyl -thien-2-yl)thioéthyl]pipéridine-3-carboxylique(3R4R) -4- [3- (KS) -Fluoro-3- (6-methoxyquinyl-4-yl) propyl] -1- [4- (3-methyl-xhien-2-yl) butyl] acid Piperidine-3-carboxylic acid (3R, 4R) -4- [3- (RS) -fluoro-3- (6-triethoxyquinolin-4-yl) propyl] -1- [2- (3-methyl-thien-1 2-yl) thioethyl] piperidine-3-carboxylic acid

Acide (3R,4R)^-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthvl -thien-2-yl)thiopropyl]pipéridine-3-carboxylique(3R, 4R) - [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-methyl-thien-2-yl) thiopropyl acid ] piperidine-3-carboxylic acid

Acide (3R,4R)^l-[3-(R,S)-fluoro-3-(6-méthoxyquinolin^-yl)propyl]-1 -[3-(thien-3-2 0 yl)propyl]pipéridine-3-carboxylique(3R, 4R) 1- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-2-yl) propyl] -1- [3- (thien-3-yl) propyl] piperidine acid -3-carboxylic acid

Acide (3R,4R)^4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(thien-3-yl)butyl]pipéridine-3-carboxylique(3R, 4R) 4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-3-yl) butyl] piperidine-acid 3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin^4-yl)propyl]-1 -[2-(thien-3-yl)thioéthyl]pipéridine-3-carboxylique 2 5 Acide (3R.4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-\-l)propyl]-1 -[3-(thien-3- yl)thiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-3-yl) thioethyl] piperidine-acid 3-Carboxylic acid (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3) - yl) thiopropyl] piperidine-3-carboxylic

Acide f3R_4R)-4-[3-(R.S)-fluoro-3-(6-méthoxyquinohn-4-\-l)propyl]-1 -[3-(für-2-yl >propyl]pipéridine-3-carboxylique3- [3- (3S) -Fluoro-3- (6-methoxyquinino-4-yl) propyl] -1- [3- (f-2-yl) propyl] piperidine-3-carboxylic acid

Acide (3R.4R)-4-[3-(R.S)-fluoro-3-(6-méthoxyquinolin-4->I)propyI]-1 -[4-(fur-2- 3 0 yl)buryl]pipéridine-3-carboxylique(3R4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-> 1) propyl] -1- [4- (fur-2-yl) buryl] piperidine acid -3-carboxylic acid

Acide (3R.4R)-4-[3-(R-S)-fluoro-3-(6-méthoxyquinolin-4-\-l)propyl]-1 -[2-ffür-2-yl )thioéthyl]pipéridine-3-carboxylique(3-4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (2-fluoro-2-yl) thioethyl] piperidine-3-acid carboxylic

Acide i3R.4R)-4-[3-(R.S)-fluoro-3-(6-méthoxyquinolin-4-\'l)propyl]-l-[3-(fur-2-I3R.4R) -4- [3- (R) S-fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-2-

K yl)thiopropyl]pipéridine-3-carboxylique 3 3 Acide (3R.4R)^-[3-(R.S)-fluoro-3-(6-méthox\quinolin-4-\l)propyl]-l-[3-(fiir-3- yl ipropyljpipéridine-3-carboxyljque 12 0 2 2 49(3R, 4R) N - [3- (RS) -Fluoro-3- (6-methoxydinolin-4-yl) propyl] -1- [3-yl] thiopropyl] piperidine-3-carboxylic acid - (3-yl) -propyl-piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 - [4-(fùr-3 - yl)butyl]pipéridine-3-caiboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (tert-3-yl) butyl] piperidine-acid 3-caiboxylique

Acide (3R,4R)-4-[3-(R,S)-fluorœ3-(6-niéthoxyquinoIin-4-yl)propyl]-1 -[2-(iur-3- yl)thioéthyl]pipéridine-3-caiboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (iur-3-yl) thioethyl] piperidine-3- acid caiboxylique

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-l -[3-(fùr-3-yl)thiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (3-yl) thiopropyl] piperidine acid- 3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinoIin-4-yl)prûpyl]-1 -[3-( 1 -méthyl-pyrrol-2-yl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinin-4-yl) propyl] -1 - [3- (1-methyl-pyrrol-2-yl) acid propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumoIm-4-yl)propyl]-l-[4-(l-méthyl-pyrrol-2-yl)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinim-4-yl) propyl] -1- [4- (1-methyl-pyrrol-2-yl) acid butyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[2-( 1 -méthyl-pyrrol-2-yl)thioéthyl]pipéridine-3-caiboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1 - [2- (1-methyl-pyrrol-2-yl) acid thioethyl] piperidine-3-caiboxylique

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-métboxyquinolin-4-yl)propyl]-l-[3-(l -méthyl-pyrrol-2-yl)Üiiopropyi]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-metboxyquinolin-4-yl) propyl] -1- [3- (1-methyl-pyrrol-2-yl) acid Üiiopropyi] piperidine-3-carboxylic acid

Acide (3R,4R>4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)prq)yl]-1 -[3-( I -méthyl-pyrro? -2-yl)propyl]pipéridine-3-caiboxylique(3R, 4R) 4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl) -1- [3- (1-methyl-pyrrole) -2- yl) propyl] piperidine-3-caiboxylique

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(î-méthyl-pyrrol-3-yl)butyl]pipéridine-3-carboxy!ique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1-methyl-pyrrol-3-yl) acid butyl] piperidine-3-carboxy! ic

Acide (3R,4R)-4-[3-(R,S)-fluor(>-3-(6-méthoxyquinobn-4-yl)propyl]-l-[2-(l-niéthyl-pyrrol-3-yl)thioéthyî]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluor (> - 3- (6-methoxyquinobn-4-yl) propyl] -1- [2- (1-methylpyrrol-3-) - (3R, 4R) - [- (3- (R, S) -fluor yl) thioéthyî] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquiixûlin-4-yl)propyl]-1 -[3-( i -méthyl-pyrrol-3-yi)Üiiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinyl-4-yl) propyl] -1- [3- (1-methyl-pyrrol-3-yl) acid) Üiiopropyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolixi-4-yl)propyl]-1 -[3-( 1,3-thiazol-2-yl)propyl]pipàidine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolix-4-yl) propyl] -1 - [3- (1,3-thiazol-2-yl) acid propyl] pipàidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluorc>-3-(6-méthoxyqumolin-4-yl)propyl]-l-[4-(l, 3-thiazol-2-yl)butyl]pipéridine-3-caiboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [4- (1,3-thiazol-2-yl) -acid ) butyl] piperidine-3-caiboxylique

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méihoxyquinoIin-4-yl)propyl]-l-[2-(l>3-tbiazol-2-yl)thioéthyl]pipéridine-3-caiboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methyloxyquinolin-4-yl) propyl] -1- [2- (1H-3-tbiazol-2-yl) acid) thioethyl] piperidine-3-caiboxylique

Acide (3R,4R)~4-[3-(R,S)-iluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l -[3-(l ,3-thiazol-2-yl)thiopropyl]pipéridine-3-caiboxylique(3R, 4R) -4- [3- (R, S) -Lluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl) acid) thiopropyl] piperidin-3-caiboxylique

Acide (3R,4R)^4-[3-(R,S)-iluoro-3-(6-méthoxyquinoiin-4-yl)propyl]-l-[3-(l-méthyl-imidazol-2-yl)propyl]pipéridine-3-carboxylique(3R, 4R) 4- [3- (R, S) -Lluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methyl-imidazol-2-yl) acid) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)^-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-( 1 -méthyl- imidazol-2-yl)butyl]pipéridine-3-carboxyIique(3R, 4R) - [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [4- (1-methylimidazol-2-yl) butyl] acid ] piperidin-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]- l-[2-(l-méthyl- imidazoi-2-yl)tbioéthyi]pipéridine-3-carboxylique 120 2 2 50(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1-methylimidazol-2-yl) acid) tbioethylpiperidine-3-carboxylic acid 120 2 2 50

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumoIiD-4-yl)propyl]-l-[3-(l-niéthyl- in3idazol-2-yl)thioprOpyI]pipéridine-3-carboxyIique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxy-quinol-4-yl) propyl] -1- [3- (1-methyl-imidazol-2-yl) acid thioprOpyI] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl- imidazol-4-yl)propyl]pipéridine-3-cafboxylique 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-mé±oxyquinoliii-4-yl)propyl]-l-[4-(3-méthyl-imidazol-4-yl)butyl]pipéridine-3-cafboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-methylimidazol-4-yl) acid propyl] piperidine-3-cafboxylic acid (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methyloxyquinolin-4-yl) propyl] -1- [4- 3-methyl-imidazol-4-yl) butyl] piperidine-3-cafboxylique

Acide (3R,4R)-4-[3-(R,S)-iluoro-3-(6-méthoxyquinoliii-4-yl)propyl]- l-[2-(3-méthyl-imidazol-4-yl)thioéthyl]pipéridine-3-caiboxylique(3R, 4R) -4- [3- (R, S) -Lluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methyl-imidazol-4-yl) acid) thioethyl] piperidine-3-caiboxylique

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-mélhoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl-io imidazol-4-yl)titiiopropyl]pipéridine-3-caiboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-melhoxyquinolin-4-yl) propyl] -1 - [3- (3-methyl) imidazol-4-yl) ) titiiopropyl] piperidin-3-caiboxylique

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-niéthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl-pyrazol 4-yl)propyl]pipéridine-3-caiboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-pyrazol-4-yl) -propyl) -acid ] piperidin-3-caiboxylique

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquiQolin-4-yl)propyl]-1 -[4-(3-méthyl-pyrazol 4-yl)butyl]pipéridine-3-carboxylique 15 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3-méthyl-pyrazol 4-yl)thioéthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquiolin-4-yl) propyl] -1- [4- (3-methyl-pyrazol-4-yl) butyl] acid ] Piperidine-3-carboxylic acid (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methyl) pyrazol-4-yl) thioethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl-pyrazol 4-yl)thiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-methyl-pyrazol-4-yl) thiopropyl acid ] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(oxazol-2-20 yl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) propyl] piperidine acid -3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(oxa2ol-2-yl)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (oxa-2-yl) butyl] piperidine-acid 3-carboxylic acid

Acide (3R,4Ry4-[3-(R,S)-fluoro-3-(6-méthoxyquinolinA-yl)propyl]-1 -[2-(oxazol-2-yl)thioéthyl]pipéridine-3-carboxylique 2 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(oxazol-2- yl)thiopropyl]pipéridine-3-caiboxylique(3R, 4Ry4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (oxazol-2-yl) thioethyl] piperidine-3-carboxylic acid (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) thiopropyl] piperidine acid 3-caiboxylique

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridin-2-yl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) propyl] piperidine-acid 3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(pyridin-2- 3 o yl)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-2-yl) butyl] acid piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolinA-yl)propyl]-1 -[3-(pyridin-2-yl)thiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-yl) propyl] -1- [3- (pyridin-2-yl) thiopropyl] piperidine-3- acid carboxylic

Acide (3R,4R)^l-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-((pyridin-3- yl)propyl]pipéridine-3-carboxylique 3 5 Acide (3R,4R)-4-[3-(R.S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(pyridin-3- yl)butyl]pipéridine-3-carboxylique 120 22 51(3R, 4R) 1- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3 - ((pyridin-3-yl) propyl] piperidine acid -3-carboxylic acid (3R, 4R) -4- [3- (RS) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-3-yl)) butyl] piperidine-3-carboxylic acid 120 22 51

Acide (3R,4R)-4-[3-(R,S)-fluoK>-3-(6-méthoxyquinoEn-4-yl)propyl]-l-[2-(pyridin-3- yl)thioéthyl]pipéridine-3-carboxyIique(3R, 4R) -4- [3- (R, S) -FluoroK) -3- (6-methoxyquinin-4-yl) propyl] -1- [2- (pyridin-3-yl) thioethyl] piperidine acid -3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-mélhoxyquinoim^4-yl)propyl3-1 -[3-(pyridin-3- yl)thiopropyl]pipéridme-3-carboxyEque 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinûlm-4-yl)propyl]-l -[3-(pyridin-4-yl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinoimid-4-yl) propyl] -1 - [3- (pyridin-3-yl) thiopropyl] piperidinic acid-3 -carboxyEque (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinim-4-yl) propyl] -1- [3- (pyridin-4-yl) propyl) -carboxylic acid ] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R)S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l -[4-(pyridin-4-yl)butyl]pipéridme-3-caiboxyEque(3R, 4R) -4- [3- (R) S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-4-yl) butyl] piperidinic acid; 3-caiboxyEque

Acide (3R,4R)-4-[3-(RîS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[5-(pyridin-4-10 yl)pentyl]pipéridme-3-caiboxyEque(3R, 4R) -4- [3- (R-S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [5- (pyridin-4-yl) pentyl] piperidin-3-acid -caiboxyEque

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-l -[2-(pyridin-2-yl)thioéthyl]pipéridine-3-caiboxyiique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [2- (pyridin-2-yl) thioethyl] piperidine acid 3-caiboxyiique

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm^-yl)propyl]-l-[2-(pyridm-4-yl)thioéthyl]pipéridine-3-caiboxyEque 15 Acide (3R,4R)-4-[3-(R,S)-iluor(>-3-(6-méthoxyquino!in-4-yl)propyl]-l -[3-(pyridin-4-yl)thiopropyl]pipéridine-3-carbox}:lique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-1-yl) propyl] -1- [2- (pyrid-4-yl) thioethyl] piperidine-3-acid Bicarboxylic acid (3R, 4R) -4- [3- (R, S) -iluor (> -3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4) yl) thiopropyl] piperidin-3-carbox} lic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(pyrii'nidin-2-yl)propyl]pipéridine-3-caiboxyEque(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyriienin-2-yl) propyl] acid piperidin-3-caiboxyEque

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumoEn-4-yl)propyl]-l -[4-(pyrimidin-2-20 yl)butyl]pipéridme-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquen-4-yl) propyl] -1- [4- (pyrimidin-2-yl) butyl] piperidinic acid -3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méîhoxyquinolin-4-yl)propyi]- l-[2-(pyrimidin-2-yl)tbiosthy]]pipéridme-3-caiboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidin-2-yl) tbiosthyl] piperidinic acid -3-caiboxylique

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolm-4-yi)propyl3-l -[3-(pyrimidin-2-yl)thiopropyl]pipéridine-3-caiboxylique 2 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6'méthoxyquinoEn-4-yl)propyl]-l-[3-(pyrnnidm-4- yl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyqumol-4-yl) propyl] -1 - [3- (pyrimidin-2-yl) thiopropyl] piperidine-3 acid -caiboxylic acid (3R, 4R) -4- [3- (R, S) -fluoro-3- (6'-methoxyquinin-4-yl) propyl] -1- [3- (pyrimidin-4-yl) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(pyrimidin-4-yî)butyl]pipéridine-3-caiboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidin-4-yl) butyl] piperidine-acid 3-caiboxylique

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l -[2-(pyrimidin-4-30 yi)thioéthyl]pipéridine-3-carboxyEque(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidin-4-yl) thioethyl] piperidine acid -3-carboxyEque

Acide (3R,4R)^-[3-(R,S)-fluoro-3-(6-méthoxyquinoEn-4-yl)propyl]-l-[3-(pyrimidin-4-yl)îhiopropyl]pipéridine-3-carboxylique(3R, 4R) - [3- (R, S) -Fluoro-3- (6-methoxyquino-en-4-yl) propyl] -1- [3- (pyrimidin-4-yl) i-propyl] -piperidine-3 -acid carboxylic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyriinidin-5-yl)propyl]pipéridine-3-carboxvîique 3 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3’(6-méthoxyquinolin-4-yl)propyl]- l-[4-(pyrimidin-5- yl)butyl]pipéridine-3-caiboxylique 120 2 2 52(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyriinidin-5-yl) propyl] piperidine acid 3-Carboxylic acid (3R, 4R) -4- [3- (R, S) -Fluoro-3 '(6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidin-5-yl) ) butyl] piperidine-3-caiboxylic 120 2 2 52

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyrimidin-5-yl)thioé&amp;yl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidin-5-yl) thioe) -acid] yl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R.S)-fluoro-3-(6-inéthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-5-yl)thiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-5-yl) thiopropyl] piperidine-3- acid carboxylic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrazin-2-yl)propyl]pipéridme-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) propyl] piperidinic acid; 3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-iluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(pyrazin-2-yl)butyl]pipéridine-3-caiboxylique(3R, 4R) -4- [3- (R, S) -Lluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrazin-2-yl) butyl] piperidine-acid 3-caiboxylique

Acide (3R,4R)-4-[3-{R,S)-fluoiO-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(pyrazin -2-yl)thioéthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrazin-2-yl) thioethyl] piperidine acid 3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrazin-2-yl)üiiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) -propiopyl] piperidine-acid 3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridazin-3-yl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) propyl] piperidine acid 3-carboxylic acid

Acide (3R,4R)^4-[3-(R.S)-fluoro-3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[4-(pyridazin-3-yl)bulyl]pipéridine-3-cafboxylique(3R, 4R) 4- [3- (RS) -Fluoro-3- (6-methoxyquinin-4-yl) propyl] -1- [4- (pyridazin-3-yl) bulyl] piperidine-3- acid cafboxylique

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-l -[2-(pyridazin-3-yl)thioé±yl]pipéridine-3-carboxy!ique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxy-iminolin-4-yl) -propyl] -1- [2- (pyridazin-3-yl) thio-yl] -acid] piperidine-3-carboxy! ic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridazin-3-yl)thiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) thiopropyl] piperidine acid 3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l -[3-(pyridazm-4-yl)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridaz-4-yl) propyl] piperidine acid 3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(pyridazin^t-yl)butyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridazin-1-yl) butyl] piperidine-acid 3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyridazin-4-yl)thioéthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridazin-4-yl) thioethyl] piperidine acid 3-carboxylic acid

Acide (3R4R)^4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-l-[3-(pyridazin-4-yl)thiopropyl]pipéridine-3-carboxylique(3R4R) 4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (pyridazin-4-yl) thiopropyl] piperidine-3- acid carboxylic

Acide (3R4R)-4-[3-(R,S)-fluoro-3-(6-méîhoxyquinolin-4-yl)propyl]-1 -[3-phényl-prop-2-ynyl]-pipéridine 3-carboxylique(3R4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenyl-prop-2-ynyl] -piperidine 3-carboxylic acid

Acide (3R,4R)-4-[3-(RS)-iluoro-3-(6-méthoxyqumolin^-yl)propyl]-1 -[3-(2-fluoro-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (RS) -Lluoro-3- (6-methoxy-trimolin-1-yl) propyl] -1- [3- (2-fluoro-phenyl) -prop-2-ynyl] acid -piperidine-3-carboxylic acid

Acide (3R4R)-4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-fluoro-phényl)- prop-2-ynyl]-pipéridine-3-carboxylique(3R4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluoro-phenyl) -prop-2-ynyl] - acid piperidine-3-carboxylic acid

Acide (3R.4R>4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-chloro-phényl)- prop-2-ynyl]-pipéridine-3-caiboxyiique 120 2 2 53(3R.4R) 4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (2-chlorophenyl) prop-2- acid ynyl] -piperidine-3-carboxylic acid 120 2 2 53

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méÜioxyquinolin-4-yl)propyl]-1 -[3-(3-chloro-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methyloxyquinolin-4-yl) propyl] -1 - [3- (3-chloro-phenyl) -prop-2 -acid] acid ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fIuoro-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-(4-chioro-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique 5 Acide (3R,4R)-4-[3-(R,S>fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l -[3-(2-méthyl-phényl)-prqp-2-ynyl]-pipéridine-3-carboxyIique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1 - [3- (4-chloro-phenyl) prop-2 -acid] acid -ynyl] -piperidine-3-carboxylic acid (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2) -methyl-phenyl) -prqp-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-l-[3-(3-méthyl-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (3-methyl-phenyl) prop-2) -acid ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(4-méthyl-phényl)-10 prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methyl-phenyl) -10 propionic acid; 2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(2-trifluorométhyl-phényl)-prop-2-ynyl]'pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (2-trifluoromethyl-phenyl) -prop-2) -acid ynyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yi)propyl]-l-[3-(3-trifluoroinéthyl-phényl)-prop-2-ynyl]-pipéridine-3-carboxy!ique 15 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumo]in-4-yl)propyl]-l-[3-(4-trifluorométhyl-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoroinethyl-phenyl) prop-2-acid) -ynyl] -piperidine-3-carboxyic acid (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxy-quin-4-yl) propyl] -1- [3- (4-trifluoromethylphenyl) -prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6~méthoxyquinolin-4-yl)propyl]-l-[3-(2-inéthoxy-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxy-phenyl) prop-2 -acid) ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-(3-méthoxy-2 o phényî)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (3-methoxy-2-phenyl) -propoic acid -2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-mélhoxyquinolin-4-yl)propyl]-l-[3-(4-méthoxy-phényl)-prop-2-ynyI]-pipéridme-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-melhoxyquinolin-4-yl) propyl] -1- [3- (4-methoxy-phenyl) -prop-2) -acid -ynyI] -pipéridme-3-carboxylic acid

Acide (3R,4R)-4-[3-(R1S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3,4-difluoro-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique 2 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3~(6-méthoxyquinolin-4-yl)propyl]-1-(3-(2,4-difluoro- phényl)-prop-2-ynyl]-pipéridine-3-carboxyiique(3R, 4R) -4- [3- (R1S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3,4-difluoro-phenyl) -prop-2 -acid] acid -ynyl] -piperidine-3-carboxylic acid (3R, 4R) -4- [3- (R, S) -fluoro-3 - (6-methoxyquinolin-4-yl) propyl] -1- (3- (2,4-Difluorophenyl) -prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-niéÜioxyquinolin-4-yl)propyl]-l-[3-(3,4-dichiorophényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methylaminoquinolin-4-yl) propyl] -1- [3- (3,4-dichlorophenyl) prop-2-acid) ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fiuoro-3-(6-méthoxyquinolin-4-yl)propyi]-1 -[3-(2,3-dichloro- 3 0 phényl)-prop-2-ynyl]-pipéridme-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichlorophenyl) acid) -prop-2-ynyl] -pipéridme-3-carboxylic acid

Acide (3Rs4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(2,4-dichloro-phényl)-prop-2-ynyl]-pipéridine-3-caiboxylique(3Rs4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (2,4-dichloro-phenyl) prop-2) -acid ynyl] -piperidine-3-caiboxylique

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,4,6-trichloro-phényl)-prop-2-ynyl]-pipéridine-3 -carboxylique 3 5 Acide (3R,4R)-4-t3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3,5-dichloro-phényl)-prop-2-ynyl]-pipéridine-3-caiboxylique 120 2 2 54(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (2,4,6-trichlorophenyl) acid prop-2-ynyl] -piperidine-3-carboxylic acid (3R, 4R) -4-t3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-dichloro-phenyl) -prop-2-ynyl] -piperidine-3-caiboxylic 120 2 2 54

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(4-chloro-3-fluorc>-phényi)-prop-2-ynyl]-pipéridine-3-caiboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3-fluorophenyl) acid ) -prop-2-ynyl] -piperidine-3-caiboxylique

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumoIin-4-yl)propyl]-1 -[3-(3-chloro-4-fluoro-phényl)-prop-2-ynyI]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinin-4-yl) propyl] -1- [3- (3-chloro-4-fluoro-phenyl) acid) -prop-2-ynyI] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méihoxyquinolin-4-yl)propyl]-1 -[3-(2-chlor&amp;-4-fluoro-phényl)-prop-2-ynyl]-pipéridine-3-caiboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (2-chloro) -4-fluoro-phenyl acid ) -prop-2-ynyl] -piperidine-3-caiboxylique

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-inéthoxyquinolin-4-yl)propyl]-1 -[3-(3-chloro-5-fluoro-phényl)-prop-2-ynyl3-pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-5-fluoro-phenyl) acid) -prop-2-ynyl3-piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-chloro-2-fluoro-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-2-fluoro-phenyl) acid) -prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-fluoro-4-méthyl·phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-4-methylphenyl) acid) -prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-chloro-3- trifluorométhyl-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3-trifluoromethyl-phenyl) acid) -prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin^-yl)propyl]-l-[3-(2-chloro-4- trifluorométhyl-phôiyl)-prop-2-ynyl3-pipéridme-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-1-yl) propyl] -1- [3- (2-chloro-4-trifluoromethyl-phenyl) - prop-2-ynyl3-pipéridme-3-carboxylic acid

Acide (3R,4R)^i-[3-(R,S)-fluoro-3~(6-méthoxyqumolin-4-yl)propyl]-1 -[3-(2-chloro-5- trifluorométhyl-phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) 1- [3- (R, S) -Fluoro-3 ~ (6-methoxyquolin-4-yl) propyl] -1- [3- (2-chloro-5-trifluoromethyl-phenyl) acid) -prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin^t-yl)propyl]-1 -[3-(5-chloro-2- méthoxy-phényl)-prop-2-ynyl]-pipéridine-3-cafboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-3-yl) propyl] -1- [3- (5-chloro-2-methoxy-phenyl) acid) -prop-2-ynyl] -piperidine-3-cafboxylique

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3,5-bis- trifluorométhyl-phényl)-prop-2-ynyl]-pipéridine-3-caiboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-bis-trifluoromethyl-phenyl) acid) -prop-2-ynyl] -piperidine-3-caiboxylique

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3,5-diméthyl- phényl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3,5-dimethylphenyl) prop) acid -2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin^1-yl)propyl]-1 -[3-(2,4-dichloro-6-méthyl-phényl)-prop-2-ynyl]-pipéridine-3-caiboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-1-yl) propyl] -1- [3- (2,4-dichloro) -6-methyl) -acrylic acid; phenyl) -prop-2-ynyl] -piperidine-3-caiboxylique

Acide (3R.4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[3-(5-chloro-thien-2-yl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinin-4-yl) propyl] -1 - [3- (5-chloro-thien-2-yl) acid -prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R.4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-ch]oro-thien-2-yl)-prop-2-ynyl]-pipéridine-3 -carboxylique(3R4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-chloro-thien-2-) -acid yl) -prop-2-ynyl] -piperidine-3-carboxylic

Acide (3R,4R)-4-[3-(R,S)-fluoro3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(5-méthyl-thien-2-yl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (5-methyl-thien-2-yl) -prop acid -2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluor©-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl-thien-2-yl)-prop-2-vnyl]-pipéridine-3-Carboxylique(3R, 4R) -4- [3- (R, S) -Fluor? -3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-methyl-thien-2-yl) -acid ) -prop-2-vnyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(thien-3-yl)-prop-2-ynyl]^ipéridine-3-carboxylique 120 2 2 55(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) -prop-2) -acid -ynyl] iperidine-3-carboxylic acid 120 2 2 55

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(l-inéthyl-pyirol-2-yl)-prop-2-ynyl]-pipéridine-3-carboxyiique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methyl-pyirol-2-yl) acid) -prop-2-ynyl] -piperidine-3-carboxylic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinoIin-4-yl)propyl]-l -[3-(l -métbyl-pyrrol-3-yl)-prop-2-ynyl]-pipéridine-3-caiboxylique 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(l,3-thia2ol-2-yl)- prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinin-4-yl) propyl] -1- [3- (1-methylbenzyl) pyrrol-3-yl) 1-Prop-2-ynyl] -piperidine-3-caiboxylic acid (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (1,3-thia2ol-2-yl) prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 >[3-(l ,3-thiazol-4-yl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (1,3-thiazol-4-yl) acid -prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-( 1,3-thiazol-5-yl)-10 prop-2-ynyl]-pipéridine-3-carboxyiique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (1,3-thiazol-5-yl) acid 10-prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumoIm-4-yl)propyl]-1 -[3-( 1 -méthyl-imidazol-2-yl)-prop-2-ynyl]-pipéridine-3-carboxyIique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxy-im-im-4-yl) -propyl] -1 - [3- (1-methyl-imidazol-2-yl) acid -prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl-imidazol-4-yi)-prop-2-ynyi]-pipàidme-3-caiboxyIique 15 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méÙioxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl-pyrazol-4-yl)-prop-2-ynyl]-pipéridine-3-carboxyEque(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-imidazol-4-yi) acid) 1-Prop-2-ynyl] -piperid-3-carboxylic acid (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-pyrazol-4-yl) -prop-2-ynyl] -piperidine-3-carboxyEque

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumoIin-4-yl)propyl]-1 -[3-(oxazol-2-yl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinin-4-yl) propyl] -1 - [3- (oxazol-2-yl) -prop-2) -acid ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(oxazol-4-yl)-prop-20 2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-4-yl) -prop-20) -acid 2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(oxazol-5-yl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (oxazol-5-yl) -prop-2 -acid] acid ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méÙîOxyquinolin-4-yl)propyl]-1 -[3-(pyridin-2-yl)-prop-2-ynyl]-pipéridine-3-carboxylique 2 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridin-3-yl)-prop- 2-ynyl]-pipéridine-3-cait>oxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methyloxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) prop-2) -acid -ynyl] -piperidine-3-carboxylic acid (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl) -prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridin-4-yl)-prop-2-ynyl]-pipéridme-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl) prop-2) -acid ynyl] -pipéridme-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-2-yl)-30 prop-2-ynyl]-pipéridine-3-carboxyiique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (pyrimidin-2-yl) propionic acid; 2-ynyl] -piperidine-3-carboxylic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqxiinolin-4-yl)propyl]-1 -[3-(pyrimidin-4-yl)-prop-2-ynyl]-pipéridine-3-caiboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxy-quinolin-4-yl) propyl] -1 - [3- (pyrimidin-4-yl) -prop-2 -acid] acid ynyl] -piperidine-3-caiboxylique

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinoIin-4-yl)propyl]-l -[3-(pyrimidin-5-yl)-prop-2-ynyl]-pipéridine-3-cait>oxylique 3 5 Acide (3R4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyi]-1 -[3-(pyrazm-2-yl)- prop-2-ynyl]-pipéridine-3-caiboxyIique Τ2θ 2 2 56(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinin-4-yl) propyl] -1 - [3- (pyrimidin-5-yl) prop-2) -acid -ynyl] -piperidine-3-carboxylic acid (3R4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazm-2-yl) -prop-2-ynyl] -piperidine-3-caiboxylic Τ2θ2 2 56

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquiiiolin-4-yl)propyl]-l-[3-(pyridazin-3-yl)-prop-2-ynyl]-pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) prop-2) -acid ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquino]in-4-yl)propyl]-1 -[3-(pyridazin-4-yl)-prop-2-ynyl]-pipéridine-3-caiboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinino-4-yl) propyl] -1 - [3- (pyridazin-4-yl) -prop acid -2-ynyl] -piperidine-3-caiboxylique

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl^)ropyl]-l-[3-phénylpropèn-2-yl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylpropen-2-yl] piperidine-3- acid carboxylic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[4-phénylbutèn-3-yl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [4-phenylbuten-3-yl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-phénylbutyl]pipéridine-3-acétiqueAcide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-fluorophényl)propyl]pipëridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4-phenylbutyl] piperidine-3-acetic acidAcid (3R, 4R) -4- [3- Methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenyl) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(2-fluorophényl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (2-fluorophenyl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-fluorophényl)propyl]pipéridme-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) propyl] piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(6-nié±oxyquinolin-4-yl)propyl]-1 -[4-(3-fluorophényl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Nie-Oxyquinolin-4-yl) propyl] -1- [4- (3-fluorophenyl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-fluorophényl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(4-fluorophényl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (4-fluorophenyl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,3-difluorophényl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl) propyl] piperidine-3-acetic acid

Acide (3R.4R)-4-[3-(6-méthoxyquinolin^-yl)propyl]-1 -[4-(2,3-difluorophényl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-1-yl) propyl] -1- [4- (2,3-difluorophenyl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxvquinolin-4-yl)propyl]-1 -[3-(2,6-difluorophényl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxvquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl) propyl] piperidine-3-acetic acid

Acide (3R.4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(2.6-difluorophényl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (2,6-difluorophenyl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-chlorophényl)propyl]pipéridme-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenyl) propyl] piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(2-chlorophényl)butyl]pipéridine- 3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (2-chlorophenyl) butyl] piperidine-3-acetic acid

Acide (3R.4R)^4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-chlorophênyl)propyl]pipéridine- 3-acétique 12 Ο ? 57(3R4R) 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenyl) propyl] piperidine-3-acetic acid 12 Ο? 57

Acide (3R,4R)-4-[3-(6-mé±oxyquinolin-4-yî)propyl]- l-[4<3-chlorophényl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methyl-oxyquinolin-4-yl) propyl] -1- [4- (3-chlorophenyl) butyl] piperidine-3-acetic acid

Acide (3R4R)-4-[3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(4<hlorophényl)propyl]pipéridine-3-acétique 5 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(4-cHorophényl)butyi]pipéridine- 3-acétique(3R4R) -4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [3- (4-chlorophenyl) propyl] piperidine-3-acetic acid (3R, 4R) -4- [Acid (3R, 4R) -4- 3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (4-chlorophenyl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]- l-[3-(2,3-dichlorophényl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichlorophenyl) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(2,3-dichlorophényl)butyl] 10 pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (2,3-dichlorophenyl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méihoxyquinoim-4-yi)propyl]-1 -[3-(2,6-dichiorophényI)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methyloxyquinoim-4-yl) propyl] -1- [3- (2,6-dichlorophenyl) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(2,6-dichlorophényl)butyî]pipéridine-3-acéüque 15 Acide (3R,4R)-4-[3-(6-méthoxyquinolin^i-yl)propyl]-l-[3-(2-méthylphényl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (2,6-dichlorophenyl) butyl] piperidine-3-acetic acid Acid (3R, 4R) -4- [3- (6-methoxyquinolin ^ i-yl) propyl] -l- [3- (2-methylphenyl) propyl] piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolm-4-yl)propyl]-1 -[4-(2-méthylphényl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [4- (2-methylphenyl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-niéthoxyquinoIin-4-yl)propyl]-1 -[5-(2-méthylphényl)pentyl] 20 pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [5- (2-methylphenyl) pentyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-mé±oxyqumoIm-4-yl)propyl]-l-[3-(3-méthylphényl)propyi]pipéridinc-3-acétique(3R, 4R) -4- [3- (6-Methylmethyl-4-yl) propyl] -1- [3- (3-methylphenyl) propyl] piperidin-3-acetic acid

Acide (3R,4R>4-[3-(6-méÎhoxyquinolin-4-yl)propyl]-1 -[4-(3-méthylphôiyl)butyl]prpéridine-3-acétique 2 5 Acide (3R,4R)-4~[3-(6-méthoxyquinoiin-4-yl)propyl]-1 -[3-(4~méthylphényl)propyl] pipéridine-3-acétique(3R, 4R) 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (3-methylphosphinyl) butyl] -prperidine-3-acetic acid (3R, 4R) -4 ~ [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenyl) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolm-4-yl)propyl]-l-[4-(4-méthylphényl)butyi]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [4- (4-methylphenyl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-méthoxyphényl)propyl] 30 pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenyl) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-inéthoxyquinolm-4-yl)propyl3-1 -[4-(2-méthoxyphényl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Inethoxyquinol-4-yl) propyl] -1 - [4- (2-methoxyphenyl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(3-méthoxyphényl)propyl]pipéridine-3-acétique 3 5 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(3-méthoxyphényl)butyl] pipéridine-3-acétique 120 22 58(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenyl) propyl] piperidine-3-acetic acid (3R, 4R) - 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (3-methoxyphenyl) butyl] piperidine-3-acetic acid 120 22 58

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(4-métboxyphényl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-metboxyphenyl) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(4-méthoxyphényl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (4-methoxyphenyl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolm^-yl)propyl]-1 -[3-(2-trifluoromélhylphényl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinol-1-yl) propyl] -1- [3- (2-trifluoromethylphenyl) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(2-trifluorométhylphényl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (2-trifluoromethylphenyl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyi]-1 -[3-(3-trifluorométhylphényl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenyl) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(3-trifluorométhylphényl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (3-trifluoromethylphenyl) butyl] piperidine-3-acetic acid

Acide (3R,4R)^-[3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(4-trifluorométhylphényl)propyl]pipéridine-3-acétique(3R, 4R) - [3- (6-Methoxyqumolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenyl) propyl] piperidine-3-acetic acid

Acide (3R,4R)^4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(4-trifluorométhylphényl)butyl]pipéridine-3-acétique(3R, 4R) 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (4-trifluoromethylphenyl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méîhoxyquinolin-4-yl)propyl]-l-[2-phénylthio-éThyrjpipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2-phenylthio-ethyl] piperidine-3-acetic acid

Acide (3R,4R)^-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-phénylthio-propyl]pipéridine-3-acétique(3R, 4R) - [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3-phenylthiopropyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2-fluorophénylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (2-fluorophenylthio) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-fluorophénylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenylthio) propyl] piperidine-3-acetic acid

Acide (3R,4R)^4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3-fluorophénylthio)éthyl]pipéridine-3-acétique(3R, 4R) 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (3-fluorophenylthio) ethyl] piperidine-3-acetic acid

Acide (3R4R)-4-[3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[3-(3-fluorophénylthio)propyl]pipéridine-3-acétique(3R4R) -4- [3- (6-Methoxyquinin-4-yl) propyl] -1- [3- (3-fluorophenylthio) propyl] piperidine-3-acetic acid

Acide (3R4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(4-fluorophénylthio)éihyl]pipéridine-3-acétique(3R4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (4-fluorophenylthio) hexyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-fluorophénylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenylthio) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2,3-difluorophénylthio)éthyl] pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (2,3-difluorophenylthio) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,3-difluorophénylthio)propyl] pipéridine-3 -acétique 12 0 2 2 59(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenylthio) propyl] piperidine-3-acetic acid 12 0 2 2 59

Acide (3R4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l -[2-(2,6-difluorophénylthio)éthyl]pipéridine-3-acétique(3R4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (2,6-difluorophenylthio) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl3-1 -[3-(2,6-difluorophénylthio)propyl jpipéridine-3-acétique 5 Acide (3R4R)-4-[3-(6-méthoxyquinolm-4-yl)propyl]-l-[2-(2-chlorophénylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenylthio) propyl] piperidine-3-acetic acid (3R4R) -4- [ 3- (6-méthoxyquinolm-4-yl) propyl] -l- [2- (2-chlorophenylthio) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-chlorophénylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenylthio) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)prppyl]-l -[2-(3-chlorophénylthio)éthyl] 10 pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (3-chlorophenylthio) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-chlorophénylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenylthio) propyl] piperidine-3-acetic acid

Acide (3R4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(4-chiorophénylthio)éthyl]pipéridine-3-acétique 15 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l -[3-(4-chlorophénylthiû)propyl]pipéridine-3-acétique(3R4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (4-chlorophenylthio) ethyl] piperidine-3-acetic acid Acid (3R, 4R) -4- [ 3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenylthi) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2,3-dichlorophénylthio)éÎhyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (2,3-dichlorophenylthio) ethyl] piperidine-3-acetic acid

Acide (3Rs4R)-4-[3-(6-méÎhoxyquinolin-4-yl)propyl]-l-[3-(2,3-dich]orophénylthio)propyl]20 pipéridine-3-acétique(3Rs4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichlorophenylthio) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2,6-dichlorophénylthio)éth>'i]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (2,6-dichlorophenylthio) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3 -(6-méthoxyquinolin-4-yI)propyl]-1 -[3 -(2,6-dichlorophénylthio)propyl]pipéridine-3-acétique 2 5 Acide (3R,4R)-4-[3-(6-méîhoxyqiünolin-4-yl)propyl]-l -[2-(2-métiiylphényiihio)éthyl] pipéridine-3-acétique(3R, 4R) -4- [3 - (6-Methoxyquinolin-4-yl) propyl] -1 - [3 - (2,6-dichlorophenylthio) propyl] piperidine-3-acetic acid Acid (3R, 4R) 4- [3- (6-Methoxy-4-yl) propyl] -1- [2- (2-methyl-phenyl) ethyl] -piperidine-3-acetic acid;

Acide (3R,4R)4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-méthylphénylthio)propyl]pipéridine-3-acétique(3R, 4R) 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenylthio) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méâoxyquinolin-4-yl)propyl]' 1 -[2-(3-méthylphényltbio)éthylj 3 o pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (3-methylphenylthio) ethyl] 3-piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méihoxyquinolin-4-yl)propyl]-1 -[3-(3-méthylphénylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methyloxyquinolin-4-yl) propyl] -1- [3- (3-methylphenylthio) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinoiin-4-yl)propyl]-1 -[2-(4-méthylphénylthio)éthyl] pipéridine-3-acétique 3 5 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-méthylphénylthio)propyl] pipéridine-3-acétique 60(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (4-methylphenylthio) ethyl] piperidine-3-acetic acid Acid (3R, 4R) - 4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenylthio) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyqumolm-4-yl)propyl]-l-[2-(2-trifluarométhylhéQylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyqumol-4-yl) propyl] -1- [2- (2-trifluaromethylethyl) ethylthio) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-triflurométhylphénylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluromethylphenylthio) propyl] piperidine-3-acetic acid

Acide (3R4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3-trifluoromélhylhénylthio)é±yl]pipéridine-3-acétique(3R4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethylphenylthio) ethyl] piperidine-3-acetic acid

Acide (3R4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-triflurométhylphénylthio)propyl]pipéridine-3-acétique(3R4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluromethylphenylthio) propyl] piperidine-3-acetic acid

Acide (3R4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(4-trifluorométhylhénylthio)éthyl]pipéridine-3-acétique(3R4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (4-trifluoromethyl-phenylthio) ethyl] piperidine-3-acetic acid

Acide (3R4R)-4-[3-(6-méthoxyqumoIin^-yl)propyl]-1 -[3-<4-îriflurométhylphénylthio)propyl]pipéridine-3-acétique(3R4R) -4- [3- (6-Methoxyquinyl-yl) propyl] -1- [3- (4-trifluoromethylphenylthio) propyl] piperidine-3-acetic acid

Acide (3R,4R>4-[3-(6-méthoxyqumolin-4-yl)propyl]-1 -[2-(2-méthoxyphénylthio)éthyl]pipéridine-3-acétique(3R, 4R) 4- [3- (6-Methoxyquolin-4-yl) propyl] -1- [2- (2-methoxyphenylthio) ethyl] piperidine-3-acetic acid

Acide (3R4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-méthoxyphénylthio)propyl]pipéridine-3-acétique(3R4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenylthio) propyl] piperidine-3-acetic acid

Acide (3R4R)^i-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3-méthoxyphénylthio)éthyl]pipéridine-3-acétique(3R4R) 1- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (3-methoxyphenylthio) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthoxyphénylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenylthio) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin^4-yl)propyl]-1 -[2-(4-mé±oxyphénylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (4-methylphenylthio) ethyl] piperidine-3-acetic acid

Acide (3R4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-méthoxyphénylthio)propyl]pipéridine-3-acétique(3R4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenylthio) propyl] piperidine-3-acetic acid

Acide (3R4R)-4-[3-(6-méthoxyquinolin^l-yl)propyl]-1 -[cyclopropylméthyl]pipéridine-3-acétique(3R4R) -4- [3- (6-Methoxyquinolin-1-yl) propyl] -1- [cyclopropylmethyl] piperidine-3-acetic acid

Acide (3R4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(cyc]opropyl)éthyl]pipéridine-3-acétique(3R4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (cyc) opropyl) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[cyclobutylméthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [cyclobutylmethyl] piperidine-3-acetic acid

Acide (3R4R)-4-[3-(6-méthoxyquinolin-4-yi)propyl]-1 -[2-(cyclobutyl)éthyl]pipéridine-3-acétique(3R4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (cyclobutyl) ethyl] piperidine-3-acetic acid

Acide (3R4R)-4-[3-(6-méthoxyquinolin^-yl)propyl]-1 -[cyclopentylméthyl]pipéridine-3- acétique *(3R4R) -4- [3- (6-Methoxyquinolin-yl) propyl] -1 - [cyclopentylmethyl] piperidine-3-acetic acid *

Acide (3R4R)-4-[3-(6-mélhoxyquinolin-4-yl)propyl]-1 -[2-(cyclopentyl)éthyl]pipéridine-3- acétique x 12 0 2 2 61(3R4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentyl) ethyl] piperidine-3-acetic acid x 12 0 2 2 61

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[cyclohexylméthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1 - [cyclohexylmethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(cyclohexyî)éthyl]pipéridine-3-acétique 5 Acide (3R,4R)-4-[3-(6-méthoxyquinoIin-4-yl)propyl]-l-[2-(cyclopropylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-3-acetic acid Acid (3R, 4R) -4- [ 3- (6-méthoxyquinoIin-4-yl) propyl] -l- [2- (cyclopropylthio) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolm-4-yl)propyl]- l-[3-(cyclopropylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [3- (cyclopropylthio) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(cyclobutylthio)éthyl3pipéridine-3-îo acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (cyclobutylthio) ethyl) piperidine-3-ol acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyqumolm-4-yl)propyl]-l-[3-(cyclobutylthiopropyl]pipàridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyqumol-4-yl) propyl] -1- [3- (cyclobutylthiopropyl) piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(cyclopentylthio)éthyl3pipéridine-3-acétique 15 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(cyclopentylthio)propyi]pipéridme- 3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-3-acetic acid (3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (cyclopentylthio) propyl] piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl3-1 -[2-(cyclohexylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperidine-3-acetic acid

Acide (3R,4R)^-[3-(6-méthoxyquinoim-4-yl)propyl]-1 -[3-(cyclohexylthio)propyl]pipéridine-20 3-acétique(3R, 4R) 1- [3- (6-Methoxyquinoim-4-yl) propyl] -1- [3- (cyclohexylthio) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-méthylthioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2-methylthioethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-méthylthiopropyl]pipéridine-3-acétique 2 5 Acide (3R,4R)-4~[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-éthylthioét}iyl]pipéridine-3- acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3-methylthiopropyl] piperidine-3-acetic acid (3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2-ethylthio] -yl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinoIm-4-yl)propyî]-1 -[3-éthylÛiiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinimin-4-yl) propyl] -1- [3-ethyl-iiopropyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(n-propylthio)éthyl]pipéridine-3-30 acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (n-propylthio) ethyl] piperidine-3-30 acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propylj-1 -[3-(n-propylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (n-propylthio) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yi)propy]]-l-[2-(n-butylthio)éthyî]pipéridme-3-acétique 3 5 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(n-butylthio)propyl}pipéridine-3- acétique 1 2 0 2 2 Ί 62(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (n-butylthio) ethyl] piperidin-3-acetic acid Acid (3R, 4R) 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (n-butylthio) propyl] piperidine-3-acetic acid 1 2 0 2 2 Ί 62

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)piOpyl]- l-[3-(thien-2-yl)prüpyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) p-propyl] -1- [3- (thien-2-yl) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyqumolin-4-yl)propyl]-l-[4-<thien-2-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquolin-4-yl) propyl] -1- [4- (2-yl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[2-(thien-2-yl)thioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolm-4-yl)propyl]-l-[3-(tbien-2-yl)thiopropyl3pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [3- (tert-2-yl) thiopropyl) -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(5-chloro-thien-2-yl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquolin-4-yl) propyl] -1- [3- (5-chloro-thien-2-yl) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyqumolm-4-yl)propyl]-1 -[4-(5-chloro-thien-2-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyqumol-4-yl) propyl] -1- [4- (5-chloro-thien-2-yl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[2-(5-chloro-thien-2-yl)thioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinin-4-yl) propyl] -1- [2- (5-chloro-thien-2-yl) thioethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(5-chloro-thien-2-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (5-chloro-thien-2-yl) thiopropyl] piperidine-3-acetic acid

Acide (3R,4R)^4-[3-(6-méthoxvquinolin-4-yl)propyl]-1 -[3-(3-chloro-thien-2-yl)propyl]pipéridine-3-acétique(3R, 4R) 4- [3- (6-Methoxvquinolin-4-yl) propyl] -1- [3- (3-chloro-thien-2-yl) propyl] piperidine-3-acetic acid

Acide (3R,4R)^î-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(3-chloro-thien-2-yl)butyl]pipéridine-3-acétique(3R, 4R) 1- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (3-chloro-thien-2-yl) butyl] piperidine-3-acetic acid

Acide (3R.4R)^4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3-chloro-thien-2-yl)thioéthyl]pipéridine-3-acétique(3R4R) 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (3-chloro-thien-2-yl) thioethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin^-yl)propyl]-1 -[3-(3-chloro-thien-2-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-1-yl) propyl] -1- [3- (3-chloro-thien-2-yl) thiopropyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(5-méthyl -thien-2-yl)propyl]pipéridine-3 -acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthien-2-yl) propyl] piperidine-3-acetic acid

Acide (3R,4R)^-[3-(6-méthoxyquinolin^i-yl)propyl]-l -[4-(5-méthyl -thien-2-yl)butyl]pipéridine-3 -acétique(3R, 4R) - [3- (6-Methoxyquinolin-1-yl) propyl] -1- [4- (5-methyl-thien-2-yl) butyl] piperidine-3-acetic acid

Acide (3RAR)-4-[3-(6-méthoxyquinolin-4-yI)propyl]-1 -[2-(5-méthyl -thien-2-yl)thioéthyl]pipéridine-3-acétique(3RAR) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (5-methyl-thien-2-yl) thioethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(5-méthyl -thien-2-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthien-2-yl) thiopropyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl -thnen-2-yl)propyl] pipéridine-3-acétique ’(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-thnen-2-yl) propyl] piperidine-3-acetic acid

Acide (3R,4R)^-[3-(6-méthoxyquinolin-4-yl)propyl]- l-[4-(3-méthyl -thien-2-yl)butyl] \ pipéridme-3-acétique 120 2 2 63(3R, 4R) - [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (3-methyl-thien-2-yl) butyl] -piperidin-3-acetic acid 120 2 2 63

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(3-méthyl -tbien-2-yl)thioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (3-methyl-tert-2-yl) thioethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]' 1 -[3-(3-méthyl -thien-2-yl)thiopropyl]pipéridine-3-acétique 5 Acide (3R,4R)-4-[3-(6-méthoxyquinoIin-4-yl)propyl]-l-[3-(thien-3-yl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-methylthien-2-yl) thiopropyl] piperidine-3-acetic acid acid ( 3R, 4R) -4- [3- (6-méthoxyquinoIin-4-yl) propyl] -l- [3- (thien-3-yl) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyqumolin-4-yl)propyl]-l-[4-(thien-3-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquolin-4-yl) propyl] -1- [4- (thien-3-yl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(thien-3-yl)thioéthyl]pipéridine-3-10 acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (thien-3-yl) thioethyl] piperidine-3-10 acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yi)propyl]- l-[3-(thien-3-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) thiopropyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyqumolm-4-yl)propyl]-l-[3-(iur-2-yl)propyl]pipéridine-3-acétique 15 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(iùr-2-yl)butyl]pipéridine-3- acétique(3R, 4R) -4- [3- (6-Methoxyqumol-4-yl) propyl] -1- [3- (iur-2-yl) propyl] piperidine-3-acetic acid Acid (3R, 4R) 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (tri-2-yl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin4-yl)propyl]-1 -[2-(fur-2-yl)thioétbyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (fur-2-yl) thioetyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]“l -[3-(fur-2-yl)thiopropyl]pipéridine-3-20 acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (fur-2-yl) thiopropyl] piperidine-3-20 acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(iur-3-yl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (iur-3-yl) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4- [3-(6-méthoxyquinolin-4-y])propyl]-1 -[4-(fur-3-yl)butyl]pipéridine-3-acétique 2 5 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propy]]-1 -[2-(fur-3-yl)thioéthyl]pipéridine-3- acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (fur-3-yl) butyl] piperidine-3-acetic acid Acid (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (fur-3-yl) thioethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(fiir-3-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (1-flu-3-yl) thiopropyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinoIin-4-yl)propylj-1 -[3-( 1 -méthyl-pyrrol-2-yl)propyl] 30 pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinin-4-yl) propyl] -1- [3- (1-methyl-pyrrol-2-yl) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1-(4-(1 -méthyl-pyrrol-2-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- (4- (1-methyl-pyrrol-2-yl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(l-méthyl-pyrrol-2-yl)thioéthyl]pipéridine-3 -acétique 3 5 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-( 1 -méthyl-pyrrol-2-yl)thiopropyî] pipéridme-3-acétique 12 0 2 2 64(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (1-methyl-pyrrol-2-yl) thioethyl] piperidine-3-acetic acid 5 Acid (3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (1-methyl-pyrrol-2-yl) thiopropyl] piperidin-3-acetic acid 12 0 2 2 64

Acide (3R,4R)-4-[3-(6-méthoxyqiiinolin-4-yl)propyl]-l-[3-(l-méthyl-pyirol-2-yl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (1-methyl-pyirol-2-yl) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-métboJcyquinolin-4-yl)propyl]-1 -[4-( 1 -méthyl-pyrrol-3-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Metbocyclinolin-4-yl) propyl] -1- [4- (1-methyl-pyrrol-3-yl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(l-méthyl-pyrrol-3-yl)ihioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (1-methyl-pyrrol-3-yl) thioethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyqumolm-4-yl)propyl]-1 -[3-( 1 -méthyl-pyrrol-3-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyqumol-4-yl) propyl] -1- [3- (1-methyl-pyrrol-3-yl) thiopropyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(thiazol-2-yl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (thiazol-2-yl) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(thiazol-2-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (thiazol-2-yl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquijnolin-4-yl)propyl]-l-[2-(thiazol-2-yl)thioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (thiazol-2-yl) thioethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-{thia2ol-2-yl)thiopropyl]pipéridine3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- {thia2ol-2-yl) thiopropyl] piperidine3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-( 1 -métbyl-imidazol-2-yl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (1-methyl-imidazol-2-yl) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinoIin^-yl)propyl]-1 -[4-( 1 -méthyl-imidazol-2-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquininyl-yl) propyl] -1- [4- (1-methyl-imidazol-2-yl) butyl] piperidine-3-acetic acid

Acide (3R4R)^-[3-(6-méthoxyquinolin-4-yl)propyI]-1-[2-( l-méthyl-imidazol-2-yl)thioéthyl]pipéridine-3-acétique(3R4R) 1- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (1-methyl-imidazol-2-yl) thioethyl] piperidine-3-acetic acid

Acide (3R4R)^[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-( 1 -méthyl-imidazol-2-yl)thiopropyl]pipéridine-3-acétique(3R4R) 3- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (1-methyl-imidazol-2-yl) thiopropyl] piperidine-3-acetic acid

Acide (3R4R)-4-[3-(6-méthoxyquinohn-A-yl)propyl]-1 -[3-(3-méthyl-imidazol^-yl)propyl]pipéridine-3-acétique(3R4R) -4- [3- (6-Methoxyquinino-A-yl) propyl] -1- [3- (3-methyl-imidazol-yl) propyl] piperidine-3-acetic acid

Acide (3R4R)^[3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[4-(3-méthyl-imidazol-4-yl)butyl]pipéridine-3-acétique(3R4R) ^ [3- (6-Methyl-quinolin-4-yl) propyl] -1- [4- (3-methyl-imidazol-4-yl) butyl] piperidine-3-acetic acid

Acide (3R4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3-méthyl-imidazol-4-yl)thioéthyl]pipéridine-3-acétique(3R4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (3-methyl-imidazol-4-yl) thioethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl-imidazol -4-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-imidazol-4-yl) thiopropyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl-pyrazol-4-yl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-pyrazol-4-yl) propyl] piperidine-3-acetic acid

Acide (3R4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(3-méthyl-pyrazol-4-yl)butyl]pipéridine-3-acétique 120 2 2 65(3R4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (3-methyl-pyrazol-4-yl) butyl] piperidine-3-acetic acid 120 2 2 65

Acide (3R,4R)-4-[3-(6-méthoxyqumolm-4-yl)piOpyl]-l-[2-(3-méthyl-pyra2ol-4-yl)thioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyqumol-4-yl) p-pyl] -1- [2- (3-methyl-pyra-2-yl) thioethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-niéthoxyquinolin-4-yl)propyl3-l-[3-(3-méthyl-pyrazol-4-yl)ihiopropyl]pipéridine-3-acétique 5 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(oxazol-2-yl)propyl]pipéridme-3- acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-pyrazol-4-yl) i-propyl] piperidine-3-acetic acid Acid (3R) 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) propyl] piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]- l-[4-(oxazol-2-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (oxazol-2-yl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méÜioxyquinolin-4-yl)propyl]-1 -[2-(oxazol-2-yl)thioéthyl]pipéridme-10 3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (oxazol-2-yl) thioethyl] piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(oxazol-2-yl)thioprOpyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) thiopropyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(pyridm-2-yl)propyl]pipéridine-3-acétique 15 Acide (3R,4R)-4-[3-(6-méûioxyquinolm-4-yl)propyl]-l-[4-(pyridin-2-yl)butyl]pipéridme-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) propyl] piperidine-3-acetic acid Acid (3R, 4R) -4- [3- (6-méûioxyquinolm-4-yl) propyl] -l- [4- (pyridin-2-yl) butyl] pipéridme-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)prOpyl]-1 -[2-(pyridin-2-yl)thioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-yl) thioethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridin-2-yl)thiopropyl] 20 pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) thiopropyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyi]-1 -[3-(pyridin-3-yl)propyl]pipéridme-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl) propyl] piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinoli«-4-yi)propyl]-1 -[4-(pyiidin-3-yl)butyl]pipàidine-3-acétique 25 Acide (3R,4R)-4-[3-(6-méîhoxyquiiiolin-4-yl)propyl]-l-[2-(pyridin-3-yl)thioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [4- (pyidin-3-yl) butyl] pipalidin-3-acetic acid (3R, 4R) ) -4- [3- (6-méîhoxyquiiiolin-4-yl) propyl] -l- [2- (pyridin-3-yl) thioethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolm-4-yI)propyl]-l -[3-{pyridin-3-yl)thiopropyI]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [3- (pyridin-3-yl) thiopropyl] piperidine-3-acetic acid

Acide (3R,4R)^4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(pyridin-4-yl)propyl]pipéridine-3-30 acétique(3R, 4R) 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl) propyl] piperidine-3-30 acetic acid

Acide (3R4R)^-[3-(6-méthoxyquinolin-4-yl)prûpylJ- l-[4-(pyridin-4-yl)butyl]pipéridine-3-acétique(3R4R) 1- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-4-yl) butyl] piperidine-3-acetic acid

Acide (3R04R)^-[3-(6-méthoxyquinolin-4-yl)propyl]-l -[5-(pyridin-4-yl)pentyl]pipéridine-3-acétique 3 5 Acide (3R,4R)-4-[3-(6-méthoxyqumolm-4-yl)propyl]-1 -[2-(pyridin-4-yl)tiuoéthyl]pipéridine-3-acétique 120 22 66(3R04R) - [3- (6-Methoxyquinolin-4-yl) propyl] -1- [5- (pyridin-4-yl) pentyl] piperidine-3-acetic acid 5 (3R, 4R) -4 -Acid [3- (6-Methoxyqumol-4-yl) propyl] -1- [2- (pyridin-4-yl) thiethyl] piperidine-3-acetic acid 120 22 66

Acide (3R,4R)-4-[3-(6-méthoxyquinolm-4-yl)propyl]-l-[3-(pyridm-4-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [3- (pyrid-4-yl) thiopropyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méîhoxyquinolin-4-yl)propyl]-l -[34pyrimidin-2-yl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1 - [(3-pyrimidin-2-yl) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolm-4-yl)propyl]-1 -[4-{pyriinidin-2-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [4- (pyriinidin-2-yl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyrimidin-2-yl)thioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidin-2-yl) thioethyl] piperidine-3-acetic acid

Acide (3R,4R)^t-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-2-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) 1- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) thiopropyl] piperidine-3-acetic acid

Acide (3R,4R)^4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-4-yl)propyl]pipéridine-3-acétique(3R, 4R) 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-4-yl) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(pyrimidin-4-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidin-4-yl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxvquinolin-4-yl)propyl]-1 -[2-(pyrimidin-4-yl)±ioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxvquinolin-4-yl) propyl] -1- [2- (pyrimidin-4-yl) ± ioethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthûxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-4-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methylquinolin-4-yl) propyl] -1- [3- (pyrimidin-4-yl) thiopropyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-5-yl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-5-yl) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(pyriinidin-5-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (pyriinidin-5-yl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinoIin-4-yl)propyl]-l -[2-{pyrimidin-5-yl)tbioétbyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinin-4-yl) propyl] -1- [2- (pyrimidin-5-yl) tbioetyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-(pyrimidin-5-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquolin-4-yl) propyl] -1- [3- (pyrimidin-5-yl) thiopropyl] piperidine-3-acetic acid

Acide (3R4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrazin-2-yl)propyl]pipéridine-3-acétique(3R4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) propyl] piperidine-3-acetic acid

Acide (3R4R)^!-[3-(6-méthoxyquinolm-4-yl)propyl]-1 -[4-(pyrazm-2-yl)butyl]pipéridine-3-acétique(3R4R) N1- [3- (6-Methoxyquinol-4-yl) propyl] -1- [4- (pyrazol-2-yl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyrazin -2-yl)thioéthyl]pipéridme-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (pyrazin-2-yl) thioethyl] piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrazin-2-yl)thiopropyl]pipéridine-3-acétique »(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) thiopropyl] piperidine-3-acetic acid »

Acide (3R4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridazin-3-yl)propyi]pipéridine-3-acétique x 12 0 2 2 67(3R4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) propyl] piperidine-3-acetic acid x 12 0 2 2 67

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(pyrida2m-3-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-2-yl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)piOpyI]-l-[2-(pyridazin-3-yl)thioéthyl]pipéridine-3-acétique 5 Acide (3R,4R)-4-[3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(pyrida2in-3-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) p10-pI] -1- [2- (pyridazin-3-yl) thioethyl] piperidine-3-acetic acid (3R, 4R) -4- [3- (6-méthoxyqumolin-4-yl) propyl] -l- [3- (pyrida2in-3-yl) thiopropyl] piperidin-3-acetic acid

Acide (3R,4R)^-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(pyridazin-4-yl)propyl]pipéridine-3-acétique(3R, 4R) - [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4-yl) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(pyridazin-4-yl)butyi]pipéridme-3-10 acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (pyridazin-4-yl) butyl] piperidin-3-10 acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyqumolin-4-yl)propyl]-l-[2-(pyrida2in-4-yl)thioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquolin-4-yl) propyl] -1- [2- (pyridinyl) -4-yl) thioethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyi]-l-[3-(pyridazin-4-yl)thiopropyl3pipéridine-3-acétique 15 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-phényl-prop-2-ynyl]-pipéridine-3- acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4-yl) thiopropyl) piperidine-3-acetic acid (3R, 4R) -4 acid [3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenyl-prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinoiin-4-yl)propyl]-1 -[3-(2-fluoro-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-fluoro-phenyl) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolm-4-yl)propyl3-l-[3-(3-fluori)-phényl)-prop-2-ynyl]-2 O pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [3- (3-fluoro) -phenyl) -prop-2-ynyl] -2-piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(6-méthoxyquinolin~4-yl)propyl]-l-[3-(4-fluoro-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-fluoro-phenyl) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(b-méthoxyqumolm-4-yl)propyl]-1 -[3-(2-chloro-phényl)-prop-2-ynyl]-pipéridine-3-acétique 2 5 Acide (3R,4R)-4~[3-(6-mctho?<yquinoIin-4-yl)propyl]-l -[3-(3-chloro-phényl)-prop-2-ynyl]- pipéridine-3-acétique(3R, 4R) -4- [3- (b-Methoxyqumol-4-yl) propyl] -1- [3- (2-chloro-phenyl) -prop-2-ynyl] -piperidine-3-acetic acid 2 (3R, 4R) -4- [3- (6-Methyl) -quinoquin-4-yl) propyl] -1- [3- (3-chloro-phenyl) -prop-2-ynyl] -piperidine- 3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-ch]oro-phényl)-prop-2-yny]]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-chl) oro-phenyl) prop-2-yn]] - piperidine-3 acid -acetic

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-méthyi-phényl)-prop-2-ynyl]-30 pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenyl) prop-2-ynyl] -3-piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-méthyl-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-phenyl) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(4-méthyl-phényl)-prop-2-ynyl]-pipéridine-3-acétique 3 5 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2-trifluorométhyl-phényl)-prop2 ynyî]-pipéridine-3-acétique 120 2 2 68(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-methyl-phenyl) -prop-2-ynyl] -piperidine-3-acetic acid 3 (3 R, 4 R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethyl-phenyl) -propyl] -piperidine-3-acetic acid 120 2 2 68

Acide (3R,4R)-4-[3-(6-méthoxyqumolm-4-yl)propyl]-l-[3-(3-triiluoromé±yl-phényl>-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyqumol-4-yl) propyl] -1- [3- (3-triiloromethyl) phenyl-prop-2-ynyl] -piperidine-3-acid acetic

Acide (3R,4R)-4-[3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(4-trifluorométhyl-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [3- (4-trifluoromethyl-phenyl) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]- l-[3-(2-méthoxy-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxy-phenyl) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R.4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthoxy-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3-4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxy-phenyl) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R>4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(4-méthoxy-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxy-phenyl) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolm-4-yl)propyl3-l-[3-(3,4-difluoro-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [3- (3,4-difluoro-phenyl) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2.4-difluoro-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,4-difluoro-phenyl) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3.4-dichIoro-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3,4-dichlorophenyl) prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2.3-dichloro-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichloro-phenyl) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,4-dichloro-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,4-dichloro-phenyl) -prop-2-ynyl] -piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,4,6-trichloro-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trichlorophenyl) prop-2-ynyl] -piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3,5-dichloro-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3,5-dichloro-phenyl) -prop-2-ynyl] -piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(4-chloro-3-fluoro-phényl)-prop-2-ynylj-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3-fluoro-phenyl) -prop-2-ynyl] -piperidine-3-acid -acetic

Acide (3R4R)-4-[3-(6-méthoxyqumolin^-yl)propyl]-l-[3-(3-chloro-4-iluoro-phényl)-prop-2-\nyl]-pipéridine-3-acétique(3R4R) -4- [3- (6-Methoxy-iminolin -yl) propyl] -1- [3- (3-chloro-4-fluoro-phenyl) -prop-2-yl] -piperidine-3 -acid acetic

Acide (3R4R)-4-[3-(6-méthoxy'qumolin-4-yl)propyl]-l-[3-(2-chloro-4-fluoro-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R4R) -4- [3- (6-Methoxy-iminolin-4-yl) propyl] -1- [3- (2-chloro-4-fluoro-phenyl) -prop-2-ynyl] -piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-chloro-5-fluorophényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-5-fluorophenyl) prop-2-ynyl] -piperidine-3-acid acetic

Acide (3R,4R)-4-[3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(4-chloro-2-fluoro-phényl)-prop-2-ynvl]-pipéridine-3-acétique *(3R, 4R) -4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [3- (4-chloro-2-fluoro-phenyl) -prop-2-yn] -1-piperidine-acid 3-acetic *

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-fluoro-4-méthyl-phé3iyl)-prop- 2-}Tiyl]-pipéridine-3-acétique 120 22 69(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-4-methyl-phenyl) -prop-2-yl] Tiyl] -piperidine Acid -3-acetic 120 22 69

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-chloro-3-trifluorométhyl-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3-trifluoromethyl-phenyl) -prop-2-ynyl] -piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]- l-[3-(2-chloro4-trifluoroméihyl-phényl)-prop-2-ynyl]-pipéridine-3-acétique 5 Acide (3R,4R)-4-[3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(2-chloro-5-trifluorOméthyl-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4-trifluoromethyl-phenyl) -prop-2-ynyl] -piperidine-3- acid Acetic acid (3R, 4R) -4- [3- (6-Methoxyquolin-4-yl) propyl] -1- [3- (2-chloro-5-trifluoromethyl-phenyl) -prop-2-ynyl] - piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolm-4-yl)propyl]-l-[3-(5-chloro-2-méthoxy-phényl)-prop-2-ynyl]-pipéridme-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [3- (5-chloro-2-methoxy-phenyl) -prop-2-ynyl] -piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyqumolm-4-yl)propyl]-l-[3-(3J5-bis-trifluorométhyl-phényl)-io prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyqumol-4-yl) propyl] -1- [3- (3H-bis-trifluoromethyl-phenyl) -io-prop-2-ynyl] -piperidine-3 -ic acid -acetic

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3,5-diinéthyl-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3,5-diinyl-phenyl) -prop-2-ynyl] -piperidine-3-acid acetic

Acide (3R,4R)-4-[3-(6-méthoxyquinoliD-4-yl)propyl]-l -[3-(2,4-dichlorc>-6-méthyl-phényl)-prop-2-ynyl]-pipéridine-3-acétique 15 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(thien-2-yl)-prop-2-ynyl]- pipéridine-3-acétiqiie(3R, 4R) -4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [3- (2,4-dichloro-6-methyl-phenyl) -prop-2-ynyl] acid -piperidine-3-acetic acid (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(5-chloro-thien-2-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (5-chloro-thien-2-yl) -prop-2-ynyl] -piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolm-4-yl)propyl]-l-[3-(3-chloro-thien-2-yl)-prop-2-ynyl]-20 pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [3- (3-chloro-thien-2-yl) -prop-2-ynyl] -20-piperidine acid -3-acetic acid

Acide (3R,4R)-4-[3-(6-méÜioxyquinoliii-4-yl)propyl]-l-[3-(5-méthyl-thien-2-yl)'prop-2-ynyl]-pipéridine-3-acéüque(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (5-methyl-thien-2-yl) prop-2-ynyl] -piperidine-acid 3-acéüque

Acide (3R,4R)-4-[3-(6-méthoxyqinnolin-4-yl)propyl]-1 -[3-(3-métliyl-thien-2-yl)-prop-2-ynyl]-pipéridine-3-acétique 2 5 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l -[3-(thien-3-yl)-prop-2-ynyl]- pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-thien-2-yl) -prop-2-ynyl] -piperidine-acid 3-acetic acid (3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop-2-ynyl] piperidine -3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[3-( 1 -méthyl-pyrrol-2-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinin-4-yl) propyl] -1- [3- (1-methyl-pyrrol-2-yl) -prop-2-ynyl] -piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(l-méthyl-pyrrol-3-yl)-prop-2- 3 0 ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (1-methyl-pyrrol-3-yl) prop-2-ynyl] - acid piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thiazol-2-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (thiazol-2-yl) prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(thiazol-4-yl)-prop-2-ynyl]-pipéridine-3-acétique 3 5 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyî]-1 -[3-(thiazol-5-yl)-prop-2-ynyl]-pipéridine-3-acétique 120 2 2 70(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (thiazol-4-yl) prop-2-ynyl] -piperidine-3-acetic acid 3 (3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (thiazol-5-yl) prop-2-ynyl] -piperidine-3-acetic acid 120 2 2 70

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(l-méthyl-imidazol-2-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (1-methyl-imidazol-2-yl) -prop-2-ynyl] -piperidine-acid 3-acetic acid

Acide (3R,4R)^4-[3-(6-mélhoxyquinolin-4-yl)piOpyl]-1 -[3-(3-méthyl-imidazol-4-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) 4- [3- (6-Methoxyquinolin-4-yl) piOpyl] -1- [3- (3-methyl-imidazol-4-yl) -prop-2-ynyl] -piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl-pyrazol-4-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-pyrazol-4-yl) -prop-2-ynyl] -piperidine-acid 3-acetic acid

Acide (3R,4R)^4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(oxazol-2-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méüioxyquinolin-4-yl)propyl]-1 -[3-(oxazol-4-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-4-yl) prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(oxazol-5-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-5-yl) prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-<pyridin-2-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquolin-4-yl) propyl] -1- [3- (pyridin-2-yl) prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R.4R)-4-[3-(6-méthoxyqumolin-4-yl)propy]]-1 -[3-(pyridin-3-yl)-prop-2-ynyl]-pipéndine-3-acétique . Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridiii-4-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4 R) -4- [3- (6-Methoxyquolin-4-yl) propyl] -1- [3- (pyridin-3-yl) prop-2-ynyl] -piperine-3-acetic acid . (3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyridi-4-yl) prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-2-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-4-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-4-yl) prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-5-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-5-yl) prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R.4R)^l-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrazin-2-yl)-prop-2-ynyl]-pipéridine-3 -acétique(3R4R) 1- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridazin-3-yl)-prop-2-ynyl]-pipéridine-3-acérique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) prop-2-ynyl] -piperidine-3-aceric acid

Acide (3R.4R)-4-[3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(pyridazm-4-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R4R) -4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [3- (pyridazm-4-yl) prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-phénylpropèn-2-yl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3-phenylpropen-2-yl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-phénylbutèn-3-yl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4-phenylbuten-3-yl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-phénylpropyl] pipéridine-3-acétique 120 2 2 71(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylpropyl] piperidine-3-acetic acid 120 2 2 71

Adde (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[4-phénylbutyl]pipéridine-3-acédqueAdde (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4-phenylbutyl] piperidine-3-acedic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-niéthoxyquinolin-4-yl)propyl]-l-[3-(2-fluoiOphényl)propyl]pipéridine-3-acéùque 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(2-fluorophényl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluoro-phenyl) -propyl] piperidine-3- acid Acetic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-fluorophenyl) butyl] piperidine- 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydiOxy-3-(6-méthoxyqumolm-4-yl)propyl]-l-[3-(3-fiuorophàiyl)propyl]pipéridine-3-acétiç[ue(3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyqumol-4-yl) propyl] -1- [3- (3-fluorophenyl) propyl] piperidine-3- acid Acetic [ue

Acide (3R4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquino]in-4-yl)propyl]'l-[4-(3-iluorophényl)10 butyi]pipéridine-3-acétique(3R4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinino-4-yl) propyl] -1- [4- (3-iluorophenyl) butyl] piperidine-3-acid -acetic

Adde (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-fluorophényl)prppyl]pipdidine-3-acétiqueAdd (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) propyl] pipdidine-3 acetic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(4-fluorophényl)butyl]pipéridm.e-3-acétique 15 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,3-difluoropbényl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-fluorophenyl) butyl] piperidyl acid; 3-acetic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluoropbenyl)) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)prapyl]-l -[4-(2,3-difluorophényl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) -propyl] -1- [4- (2,3-difluorophenyl) butyl] piperidine-acid 3-acetic acid

Acide(3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl3-l-[3-(2,6-2 o difluorophényl)propyl]pipéridine-3-acéiique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl) propyl] piperidine acid -3-acéiique

Acide (3R,4R>4-[3-(R,S)-hydroxy-3-(6-métboxyquinolin-4-yl)propyl]-1 -[4-(2,6-difluorophényl)butyl]pipéridine-3-acétique(3R, 4R) 4- [3- (R, S) -hydroxy-3- (6-metboxyquinolin-4-yl) propyl] -1- [4- (2,6-difluorophenyl) butyl] piperidine-3 acid -acetic

Acide (3R,4R)-4-[3-(R,S)-hydiOxy-3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[3-(2-chlorophényl)propyl]pipéridine-3 -acétique 2 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3'<6-méthoxyquinolin-4-yl)propyl]-l -[4-(2-cHorophényl) butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinin-4-yl) propyl] -1- [3- (2-chlorophenyl) propyl] piperidine-3-acid - Acetic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3 '(6-methoxyquinolin-4-yl) propyl] -1- [4- (2-chlorophenyl) butyl] piperidine -3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-chlorophényl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenyl) propyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R,S)-hydiOxy-3-(6-méthoxyquinolm-4-yl)propyl]-l-[4-(3-ch]orophényl) 3 o butyl]pipëridine-3-acétique(3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [4- (3-chlorophenyl) 3-butyl] acid piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-chlorophényl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenyl) propyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(4-chiorophényl)butyi]pipéridine-3-acétique 3 5 Acide (3R,4R)-4-f3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[3-(2,3-dichlorophényl)propyI]pipéridine-3-acétique 12 0 2 2 72(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-chlorophenyl) butyl] piperidine-3- acid Acetic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichlorophenyl) propyl] piperidine-3-acetic 12 0 2 2 72

Acide(3R,4R)-4-[3-<R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-l-[4-(2,3- dichIorophényl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- <R, S) -hydroxy-3- (6-methoxyquolin-4-yl) propyl] -1- [4- (2,3-dichlorophenyl) butyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-inéthoxyqumolin-4-yl)propyl]-1 -[3-(2,6-dichlorophényl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-ethoxyquinolin-4-yl) propyl] -1- [3- (2,6-dichlorophenyl) propyl] piperidine acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(2,6-dichlorophényî)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-dichlorophenyl) butyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-méthylphényl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenyl) propyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(2-méthylphényl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-methylphenyl) butyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méùioxyquinolin-4-yl)propyl]-1 -[5-(2-méthylphényl)pentyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [5- (2-methylphenyl) pentyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyqiiinolin-4-yl)propyl]-1 -[3-(3-méthylphényl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenyl) propyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin^-yl)propyl]-1 -[4-(3-méthylphényl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-1-yl) propyl] -1- [4- (3-methylphenyl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl3-l-[3-(4-méthylphényl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenyl) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoliji-4-yl)propyl]-1 -[4-(4-méthylphényl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [4- (4-methylphenyl) butyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-méthoxy-phényl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenyl) propyl] piperidine acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(2-méthoxy-phényl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-methoxy-phenyl) butyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-(3-méthoxy-phényl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (3-methoxy-phenyl) propyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-mé±oxyquinolin^4-yl)propyl]-1 -[4-(3-méthoxy-phényl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methyloxyquinolin-4-yl) propyl] -1- [4- (3-methoxy-phenyl) butyl] acid piperidin-3-acetic acid

Acide (3R.4R)-4-[3-(KS)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-(4-méthoxy-phényl)propyl]pipéridine-3-acétique(3-4R) -4- [3- (KS) -hydroxy-3- (6-methoxy-iminolin-4-yl) propyl] -1- [3- (4-methoxy-phenyl) propyl] -piperidine-3- (4R), (3- (4R acetic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(4-méthoxy-phényl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-methoxy-phenyl) butyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-trifluoro-méthylphényl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethylphenyl) propyl] piperidine acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(2-trifluoro- méthylphény])butyl]pipéridmè-3-acétique 120 22 ’ 73(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-trifluoromethylphenyl)) butyl] piperidene acid -3-acetic 120 22 '73

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-iriiluoro-méthylphényl)propyl]pipéridme-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-iriiluoromethylphenyl) propyl] piperidinic acid; 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(3-trifluoro-méthylphényl)butyl]pipéridme-3-acétique 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yî)propyl]-1 -[3-(4-trifluoro- méthylphényl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-trifluoromethylphenyl) butyl] piperidinic acid; 3-acetic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenyl)) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-<6-méthoxyquinoIin-4-yl)propyl]-l-[4-(4-trifluoro-méthylphényl)butyl]pipàidine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinin-4-yl) propyl] -1- [4- (4-trifluoromethylphenyl) butyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-phéQylthio-10 éthyljpipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-phenylthio-ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[3-phénylthio-propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylthiopropyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-métboxyquinolin-4-yl)propyl]-l-[2-(2-fluoro-phénylthio)éthyl]pipéridine-3-acétique 15 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl3-l-[3-(2-fluorophénylthio)propyi]pipéridme-3-acéüque(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-metboxyquinolin-4-yl) propyl] -1- [2- (2-fluoro-phenylthio) ethyl] piperidine-acid 3-acetic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenylthio) propyl] piperidin -3-acéüque

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolm-4-yl)propyl]-l -[2-(3-fluoro-phényltMo)éthyljpipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyqumol-4-yl) propyl] -1- [2- (3-fluoro-phenyl) -methyl) -piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R,S>hydroxy-3-(6-méthoxyquinolm-4-yl)propyî]-l -[3-(3-fluoro-20 phénylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (3-fluoro-phenylthio) propyl] piperidine- 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méîhoxyqiiinolin-4-yl)propyl]-1 -[2-(4-iluoro-phénylthio)éthyl]pipéridme-3~acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methyloxyquinolin-4-yl) propyl] -1- [2- (4-fluoro-phenylthio) ethyl] piperidinic acid; 3 ~ acetic

Acide (3R,4R)-4-[3-(R,S>-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-l-[3-(4-fluoro-phényltHo)propyl]pipéridine-3-acétique 2 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[2-(2,3-difluoro- phénylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (4-fluoro-phenyl) -H-propyl] piperidine-acid 3-acetic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-difluoroacetate) - phenylthio) ethyl] piperidine-3-acetic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,3-difluoro-phényîthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluoro-phenylthio) propyl] acid piperidin-3-acetic acid

Acide (3R,4R)jA[3-(RS)-hydroxy-3-(6-méthoxyquinolin^i-yî)propyl]-1 -[2-(2,6-difluoro-30 phénylthio)éthyl]pipéridine-3-acétique(3R, 4R) -A [3- (RS) -hydroxy-3- (6-methoxyquinolin-1-yl) propyl] -1- [2- (2,6-difluoro-phenylthio) ethyl] piperidine-3 acid -acetic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,6-difluoro-phénylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluoro-phenylthio) propyl] acid piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2-chlorophényl-thio)éthyl]pipéridine-3-acétique 3 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-chlorophényl- thio)propyl]pipéridine-3-acétique 12 0 2 74(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-chlorophenylthio) ethyl] piperidine-acid 3-acetic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenylthio) ) propyl] piperidine-3-acetic acid 12 0 2 74

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-l-[2-(3-chlorophénylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquolin-4-yl) propyl] -1- [2- (3-chlorophenylthio) ethyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-inéthoxyquinolin-4-yl)propyl]-l -[3-(3-chlorophénylthio)propyl]pipéridme-3-acétique 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[2-(4-chlorophényl tbio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenylthio) propyl] piperidin-3- acid Acetic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquolin-4-yl) propyl] -1- [2- (4-chlorophenylthio) ethyl] piperidine -3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(4-chlorophénylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (4-chlorophenylthio) propyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2,3-dichloro-îo phénylthio)éthyl]pipéridine-3-acéüque(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-dichloro-1-phenylthio) ethyl acid ] piperidin-3-acéüque

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,3-dichloro-phénylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichloro-phenylthio) propyl] acid piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2,6-dichloro-phénylthio)éthyl]pipéridine-3-acétique 15 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinobn-4-yl)propyl]-1 -[3-(2,6-dichloro- phénylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-dichloro-phenylthio) ethyl] acid Piperidine-3-acetic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinob-4-yl) propyl] -1- [3- dichlorophenylthio) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquiiiolm-4-yl)propyl]-1 -[2-(2-méthyl-phénylthio)éîhyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxy-4-yl) -propyl] -1- [2- (2-methyl-phenylthio) hexyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinobn-4-yl)propyl]-1 -[3-(2-métbyl-2 o phénylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinob-4-yl) propyl] -1- [3- (2-methyl-2-phenylthio) propyl] acid piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumobn-4-yl)propyl]-1 -[2-(3-méthyl-phénylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxybimob-4-yl) propyl] -1- [2- (3-methyl-phenylthio) ethyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl-phénylthio)propyl]pipéridine-3-acétique 2 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinobn-4-yl)propyl]-1 -[2-(4-méthyl- phénylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-phenylthio) propyl] piperidine-acid 3-acetic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinob-4-yl) propyl] -1- [2- (4-methylphenylthio) ) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-iné±oxyquinobn-4-yl)propyl]-1 -[3-(4-méthyl-phénylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-ineoxyquinobut-4-yl) propyl] -1- [3- (4-methyl-phenylthio) propyl] acid piperidin-3-acetic acid

Acide (3R,4R) A-[3-(R,S)-hyckoxy-3-(6-méthoxyqumolin-Ayl)propyl]-1 -[2-(2-trifluoro 3 o méthylhénylthio)éthyl]pipéridine-3-acétique(3R, 4R) -A- [3- (R, S) -Hycoxy-3- (6-methoxy-iminolin-Ayl) -propyl] -1- [2- (2-trifluoro-3-methylhienylthio) ethyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolinA-yl)propyl]-1 -[3-(2-trifluro-méthylphénylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-yl) propyl] -1- [3- (2-trifluoromethylphenylthio) propyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinobn-4-yl)propyl]-1 -[2-(3-trifluoro-méthylhénylthio)éthyl]pipéridine-3-acétique * 3 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-trifluro- méthylphénylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinob-4-yl) propyl] -1- [2- (3-trifluoromethyl-phenylthio) ethyl] piperidine-acid 3-acetic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluro- methylphenylthio) propyl] piperidine-3-acetic acid

12022W 7512022W 75

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-niéthoxyquinolm-4-yl)propyl]- l-[2-(4-trifluoro-méthylhéaylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [2- (4-trifluoromethylhe) thio] ethyl] piperidine acid- 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoim-4-yl)propyl]-1 -[3-(4-trifluro-méthylphényltbio)propyl]pipéridme-3-acétique 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2-méthoxy- phénylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinoim-4-yl) propyl] -1- [3- (4-trifluoromethylphenylbio) propyl] piperidinic acid; 3-acetic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methoxyphenylthio)) ethyl] piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-métboxy-phénylthio)propyl3pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-metoxyphenylthio) propyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-l-[2-(3-méthoxy-10 phénylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [2- (3-methoxy-phenylthio) ethyl] piperidine acid -3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-bydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[3-(3-méthoxy-phénylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -bydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxy-phenylthio) propyl] piperidine-acid 3-acetic acid

Acide (3R,4R>4-[3-(R,S)-hydroxy-3-{6-méthoxyqumolin-4-yl)propyl3-l-[2-(4-méthoxy-phénylthio)éthyl]pipéridine-3-acétique 15 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-inéthoxyqumolin-4-yl)propyl]"l-[3-(4-niéùioxy-phénylthio)propylJpipéridine-3-acétique(3R, 4R) 4- [3- (R, S) -hydroxy-3- (6-methoxyquolin-4-yl) propyl] -1- [2- (4-methoxy-phenylthio) ethyl] piperidine-3- acid Acetic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxy-iminolin-4-yl) propyl] -1- [3- (4-nitrioxy-phenylthio) propyl] -piperidine- 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-inéthoxyquinolin-4-yl)propyl]-l-[cyclopropyl-méthyl]pipéridine-3-acéùque(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclopropylmethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(cyclopropyl) 20 éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopropyl) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méîhoxyquinoIin-4-yl)piOpyl]-1 -[cyclobutylméthyl]pipéridine-3-acétique ·(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) p-pyl] -1- [cyclobutylmethyl] piperidine-3-acetic acid ·

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -p-(cyclobutyl)éthyl]pipéridine-3-acétique 2 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méÛioxyquiaolin-4-yl)propyl]- l-[cyclopentylmétbyl] pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - (- cyclobutyl) ethyl] piperidine-3-acetic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methyloxyquiaolin-4-yl) propyl] -1- [cyclopentylmethyl] piperidine-3-acetic acid

Acide (3R,4R) ^4-[3-(R,S)-hydroxy-3-(6-métboxyquinolin-4-yl)propyl]-1 -[2-(cyclopentyl)thyl]pipéridine-3-acétique(3R, 4R) 4- [3- (R, S) -hydroxy-3- (6-metboxyquinolin-4-yl) propyl] -1- [2- (cyclopentyl) thyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(RS)-hydroxy-3-(6-méthoxyqumolm-4-yi)propyl]-1 -[cyclohexyhnétbyl]30 ipéridine-3-acétique(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyqumol-4-yl) propyl] -1 - [cyclohexy-butyl] -teridine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méÛioxyquinolin-4-yl)propyl]-1 -[2-(cyclohexyl)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methyloxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yî)propyl]-1 -[2-(cyciopropylthio)éthyl]pipéridine-3-acétique 3 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(cyclopropylîhio) propyl]pipéridine-3-acétique 76 12 0 2 2(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyciopropylthio) ethyl] piperidine-3-acetic acid 3 (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopropylthio) propyl] piperidine-3-acetic acid 76 12 0 2 2

Acide (3R,4R)-4-[3-(RS)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-l -[2/cyclobutylthio)éthyl]pipàidme-3-acétique(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- (2-cyclobutylthio) ethyl] pipalidin-3-acetic acid

Acide (3R4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(cyclobutylthio-propyl]pipéridine-3-acétique(3R4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclobutylthio-propyl) piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S}-hydroxy-3-(6-mélhoxyquinoIin-4-yl)propyl]-1 -[2-(cyclopentylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methyloxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquiiiolin-4-yl)propyl]-l -[3-(cyclopenÎyhhio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopenylchio) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(RS)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(cyclohexylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-inéÙioxyquinolin-4-yl)propyl]-1 -[3-(cyclohexylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-acetioquinolin-4-yl) propyl] -1- [3- (cyclohexylthio) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(RS)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-méthylthioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-methylthioethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(RS)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-méthylthio-propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-methylthio-propyl] piperidine-3-acetic acid

Acide (3R,4R)^4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-éthylthioéthyl]pipéridine-3-acétique(3R, 4R) 4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-ethylthioethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(RS)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-éthylthiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-ethylthiopropyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(RS)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(n-propylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (n-propylthio) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(n-propylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (n-propylthio) propyl] piperidine-3- acid acetic

Acide (3R4R)-4-[3-(RS)-hydroxy-3-(6-méihoxyquinolin-4-yl)propyl]-1 -[2-(n-butylthio)éthyl]pipéridine-3-acétique(3R4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (n-butylthio) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(n-butylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R) S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (n-butylthio) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(RS)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(thien-2-yl)prüpyl]pipéridine-3-acétique(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (thien-2-yl) propyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(RS)-hydroxy-3-(6-méthoxyqumolm-4-yl)propyl]-1 -[4-(thien-2-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyqumol-4-yl) propyl] -1 - [4- (thien-2-yl) butyl] piperidine-3- acid acetic

Acide (3R,4R)^-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[2-(thien-2-yl) thioéthyl]pipéridine-3-acétique(3R, 4R) - [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperidine-3-acid -acetic

Acide (3R,4R)-4-[3-(RS)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(thien-2- yl)thiopropyl]pipéridine-3-acétique 120 77(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) thiopropyl] piperidine-3- acid acetic 120 77

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-niéthoxyquinolin-4-yl)prûpyl]- l-[3-(5-chloro-tbien-2-yl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chloro-tert-2-yl) acid) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-inéthoxyquinoIm-4-yl)propyl]-1 -[4-(5-chloro-thien-2-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-ethoxyquinino-4-yl) propyl] -1 - [4- (5-chloro-thien-2-yl) acid butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(5-chloro-thien-2-yl)thioéthyl]pipéridme-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (5-chloro-thien-2-yl) acid) thioethyl] pipéridme-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(5-chloro-thien-2-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chloro-thien-2-yl) acid) thiopropyl] piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(3-chloro-ihien-2-yl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (3-chloro-1-yl) -2-yl) acid propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-métboxyquinolin-4-yl)propyl]-1 -[4-(3-chloro-thien-2-yl)butyl]pipéridine-3-acéüque(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-metboxyquinolin-4-yl) propyl] -1- [4- (3-chloro-thien-2-yl) acid butyl] piperidine-3-acéüque

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(3-ch3ora-thien-2-yl)thioéthyl]pipéridme-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chloro-thien-2-yl) acid) thioethyl] pipéridme-3-acetic acid

Acide (3R,4R}-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolm-4-yl)propyl]-l-[3-(3-chloro-thien-2-yl)thiopropyl3pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyqumol-4-yl) propyl] -1- [3- (3-chloro-thien-2-yl) acid) thiopropyl3pipéridine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-inéthoxyquinolin-4-yl)propyl]-1 -[3 -(5-méthyl -thien-2-yl)propyl]pipéridme-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3 - (5-methylthien-2-yl) acid propyl] pipéridme-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[4-(5-méthyl -thien-2-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [4- (5-methylthien-2-yl) acid butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)~b.ydroxy-3-(6-méthoxyqumolin-4-y])propyl]-l-[2-(5-méthyl-thien-2-y 1 )thioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) - b.hydroxy-3- (6-methoxyqumolin-4-y)) propyl] -1- [2- (5-methylthien-2 -acid] acid -y 1) thioethyl] piperidine-3-acetic

Acide (3R54R)-4-[3~(R3S)-hydroxy-3-(6-méthox)quinolin-4-yl)propyl]- l-[3-(5-méthyl -thien-2-yl)thiopropyl]pipéiidine-3-acétique(3R54R) -4- [3 - (R3S) -hydroxy-3- (6-methoxy) quinolin-4-yl) propyl] -1- [3- (5-methylthien-2-yl) thiopropyl] acid pipéiidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-l-[3-(3-méthyl-thien-2-yl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (3-methylthien-2-yl) acid) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[4-(3-méthyl -thien-2-yl)butyl]pipéridine-3 -acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [4- (3-methylthien-2-yl) acid butyl] piperidine-3-acetic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl3-1 -[2-(3-méthyl -thien-2-yl)thioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (3-methylthien-2-yl) thioethyl) acid ] piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-méthyl-thien-2-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylthien-2-yl) acid) thiopropyl] piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-(thien-3-yl) propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (thien-3-yl) propyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(thien-3-yl) butyl]pipéridine-3-acétique 1 2 0 2 2 78(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-3-yl) butyl] piperidine-acid 3-acetic acid 1 2 0 2 2 78

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolm-4-yl)propyl]-l-[2-(tbien-3-yl)tMoéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxy-im-4-yl) propyl] -1- [2- (tert-3-yl) methyl] piperidine acid; 3-acetic acid

Acide (3R,4R)-4-[3-(RS)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(thien-3-yl)thiopropyl]pipéridme-3-acétique(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) thiopropyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-{R,S)-hydroxy-3-(6-niéthoxyqumoIin-4-yl)propyl]-1 -[3-(far-2-yl)propyl]pipéridme-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxy-4-yl) propyl] -1- [3- (far-2-yl) propyl] piperidinic acid; 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[4-(fur-2-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [4- (fur-2-yl) butyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-xnéthoxyqumolin-4-yl)propyl]-1 -[2-(fur-2-yl)tbioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxymolin-4-yl) propyl] -1- [2- (fur-2-yl) tbioethyl] piperidine acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-niéthoxyquinolin-4-yl)propyl]-1 -[3 -(fur-2-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3 - (fur-2-yl) thiopropyl] piperidine acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[3-(fur-3-yl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methyloxyquinolin-4-yl) propyl] -1- [3- (fur-3-yl) propyl] acid piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-l -[4-(fur-3-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [4- (fur-3-yl) butyl] piperidine-acid 3-acetic acid

Acide (3R,4R)^4-[3-(R,S)-hydroxy-3-(6-métboxyquiiiolin^l-yl)propyl]-l-[2-(iur-3-yl)thioéîhyl]pipéridine-3-acétique(3R, 4R) 4- [3- (R, S) -hydroxy-3- (6-metboxyquinolin-1-yl) propyl] -1- [2- (iur-3-yl) thioheyl] piperidine acid; 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[3-(iùr-3-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methyloxyquinolin-4-yl) propyl] -1- [3- (1H-3-yl) thiopropyl] acid piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-( 1 -méthyl-pyrrol-2-yl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (1-methyl-pyrrol-2-yl) acid propyl] piperidine-3-acetic acid

Acide (3R_4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-( 1 -méthyl-pyrrol-2-yl)butyl]pipéridine-3-acétique(3R_4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1-methyl-pyrrol-2-yl) butyl] acid piperidin-3-acetic acid

Acide (3R,4R)^-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-( 1 -méthyl-pyrrol-2-yl)thioéîhyl]pipéridine-3 -acétique(3R, 4R) - [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1-methyl-pyrrol-2-yl) thioheyl) acid ] piperidine-3 -acetic

Acide (3R,4R)^-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin^-yl)propyl]-1 -[3-( 1 -méthyl-pyrrol-2-yl)thiopropyl]pipéridine- 3 -acétique(3R, 4R) - [3- (R, S) -hydroxy-3- (6-methoxyquinolin-1-yl) propyl] -1 - [3- (1-methyl-pyrrol-2-yl) thiopropyl] acid piperidine-3-acetic acid

Acide (3R,4R)^4-[3-(RS)-hydroxy-3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[3-( 1 -méthyl-pwol- 2- yl)propyl]pipéridine-3-acétique(3R, 4R) 4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methyl-pwol-2-yl) acid) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(RS)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[4-( 1 -méthyl-pyrrol- 3- yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [4- (1-methyl-pyrrol-3-yl) butyl] acid piperidin-3-acetic acid

Acide (3R.4R)-4-[3-(RS)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-( 1 -méthyl-pyrrol-3-yl)thioéthyl]pipéridine-3<-acétique(3-4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1-methyl-pyrrol-3-yl) thioethyl] acid piperidin-3 <-acetic acid

Acide (3R4R)-4-[3-(RS)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3 -( 1 -méthyl-pyrrol- 3-yl)thiopropyl]pipéridine-3-acétique 120 2 2 79(3R4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3 - (1-methyl-pyrrol-3-yl) thiopropyl] piperidine acid 3-acetic 120 2 2 79

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méùioxyquiDolin-4-yl)propyI]-1 -[3-(thiazol-2-yl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methyloxy) -Dolin-4-yl) propyl] -1- [3- (thiazol-2-yl) propyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[4-(tbiazol-2-yl)butyl]pipéridine-3-acétique 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(thiazol-2-yl)thioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (tbiazol-2-yl) butyl] piperidine acid 3-acetic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thiazol-2-yl)) thioethyl] piperidine-3-acetic acid

Acide (3R,4R}4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(ihiazol-2-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) 4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-thiazol-2-yl) thiopropyl] piperidine acid -acetic

Acide (3R,4R)4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-l-[3-(l-mélhyl-10 imidazol-2-yl)propyl]pipéridme-3-acétique >(3R, 4R) 4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (1-methyl-10-imidazol-2-yl) acid) propyl] piperidin-3-acetic acid>

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-( 1 -méthyl-ixnidazol-2-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [4- (1-methyl-ixnidazol-2-yl) acid butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoEn-4-yl)propyl]-l-[2-(l-méthyl-imidazol-2-yl)tbioéthyl]pipéridine-3-acétique 15 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(l-méthyl·imidazol-2-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinin-4-yl) propyl] -1- [2- (1-methyl-imidazol-2-yl) acid) [3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1H) -benzylethyl) piperidine-3-acetic acid · methyl imidazol-2-yl) thiopropyl] piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-niéthyl-inûdazol4-yl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-imidazol-4-yl) propyl] acid piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(3-méthyl-20 imidazol-4-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [4- (3-methyl-imidazol-4-yl) -acid ) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3-méthyl-imidazol-4-yl)thioéîhyl]pipéridme-3-'acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methyl-imidazol-4-yl) acid) thioéîhyl] pipéridme-3-'acétique

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-méihyl-imidazol-4-yl)tbiopropyl]pipéridine-3-acétique 2 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl- pyrazol-4-yl)propyl3pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylimidazol-4-yl) acid) tbiopropyl] piperidine-3-acetic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3) methyl-pyrazol-4-yl) propylpiperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoIin-4-yl)propyl]-l -[4-(3-méthyl-p)Tazo]-4-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinin-4-yl) propyl] -1 - [4- (3-methyl-p) azo] - acid yl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3-méthyl- 3 o pyrazol-4-yl)thioéthyI3pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (3-methyl-3-pyrazol-4- (3R, 4R) -acid] yl) thioéthyI3pipéridine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]- l-[3-(3-méthyl-pyrazol-4-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxy-iminolin-4-yl) propyl] -1- [3- (3-methyl-pyrazol-4-yl) -acid thiopropyl] piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyi]-1 -[3-(oxazol-2- y])propy]]pipéridine-3-acétique 3 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(oxazol-2- yi)butyl]pipéridine-3-acétique 120 2 2 80(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) propyl]] acid Piperidine-3-acetic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (oxazol-2) - yi) butyl] piperidine-3-acetic 120 2 2 80

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoliii-4-yl)propyl]-1 -[2-(oxazol-2-yl)tbioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (oxazol-2-yl) benzo] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(b-méthoxyquinoIin-4-yl)propyl]-1 -[3-(oxazol-2-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (b-methoxyquinin-4-yl) propyl] -1- [3- (oxazol-2-yl) thiopropyl] piperidine acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyqmnolin-4-yl)propyl]-1 -[3-(pyridin-2-yl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxy-iminolin-4-yl) propyl] -1- [3- (pyridin-2-yl) propyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[4-(pyridin-2-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinin-4-yl) propyl] -1- [4- (pyridin-2-yl) butyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquniolin-4-yl)propyl]-1 -[2-(pyridin-2-yl)thioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-yl) thioethyl] piperidine acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridm-2-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) thiopropyl] piperidine acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridin-3-yl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl) propyl] piperidine acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,£)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(pyridin-3-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, e) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-3-yl) butyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-mé±oxyquinolin-4-yl)propyI]-1 -[2-(pyridin-3-yl)thioé±yl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methyloxyquinolin-4-yl) propyl] -1- [2- (pyridin-3-yl) thio] acid yl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(pyridin-3-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (pyridin-3-yl) thiopropyl] piperidine acid 3-acetic acid

Acide (3R,4R)^i-[3-(R,S)-hydroxy-3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[3-(pyridin-4-yl)propyl]pipéridine-3-acétique(3R, 4R) 1- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl) propyl] acid piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-mé±oxyqumolin^l-yl)propyl]-l -[4-(pyridin-4-yl)butyl]pipëridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methyloxymolin-1-yl) propyl] -1- [4- (pyridin-4-yl) butyl] acid piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin^-yl)propyl]-l -[5-(pyridin-4-yl)pentyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxy-iminolin-2-yl) propyl] -1- [5- (pyridin-4-yl) pentyl] piperidine-3 acid -acetic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[2-(pyridin-4-yl)thioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-4-yl) thioethyl] acid piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridin-4-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl) thiopropyl] piperidine acid 3-acetic acid

Acide (3R,4R)^4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(pyrimidin-2-yl)propyl]pipéridine-3-acétique(3R, 4R) 4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) propyl] piperidine acid; 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxy?quinolin-4-yl)propyl]-1 -[4-(pyrimidin-2-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidin-2-yl) butyl] acid piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-bydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(pyrimidin-2-yl) thioéthyl]pipéridine-3-acétique ’20 22 81(3R, 4R) -4- [3- (R, S) -Bydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidin-2-yl) thioethyl] piperidine acid 3-acetic '20 22 81

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquiiiolin-4-yl)propyl]-1 -[3-(pyrimidin-2-yl)thiopropyl]pipéridme-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) thiopropyl] piperidinic acid; 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(pyrimidin-4-yl)propylJpipéridine-3-acéiique 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(pyrimidm-4-yl)butyljpipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-4-yl) propyl] piperidine-3- acid Acetic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidin-4-yl) butyl] piperidine 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(pyrijmidin-4-yl)tbioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidin-4-yl) benzo] piperidine acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(pyrimidin-4-yl)îo thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-4-yl) thiopropyl] piperidine acid -3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl3-l-[3-(pyrimidin-5-yl)propyljpipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-5-yl) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[4-(pyrixnidin-5-yl)butyl]pipéridine-3-acétique 15 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(pyrimidin-5-yl)tbioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrixnidin-5-yl) butyl] piperidine-acid 3-acetic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidin-5-yl)) tbioéthyl] piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-inéthoxyquinolin-4-yl)propylj-1 -[3-(pyrirnidin-5-yl) _thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-5-yl) thiopropyl] piperidine-3-acid -acetic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrazin-2-yl) 20 propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) propyl] piperidine acid -3-acetic acid

Acide (3R,4R)A-[3-(R,S)-hydroxy-3-(b-méthoxyquinoliii-4-yl)propyl]-1 -[4~(pyrazm-2-yl)buty]]pipéridine-3 -acétique(3R, 4R) -A- [3- (R, S) -hydroxy-3- (b-methoxyquinolin-4-yl) propyl] -1- [4 - (pyrazm-2-yl) butyl] piperidine acid 3 -acetic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-roéthoxyquinolm-4-yl)propyl]- l-[2-(pyrazin -2-yl)thioéthyl]pipéridine-3-acétique 2 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-^yrazin-2-yl) thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [2- (pyrazin-2-yl) thioethyl] piperidine acid 3-acetic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-yrazin-2-yl] thiopropyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-mêîhoxyquinolin-4-yl)propyl]-1 -[3-(pyridazin-3-yl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) propyl] piperidine acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(pyridazin-3-yl)30 butyl3pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridazin-3-yl) butyl] piperidine-3-acid -acetic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoXyquinolin-4-yl)propyl]-1 -[2-(pyridazin-3-yl)thioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methyl-quinolin-4-yl) propyl] -1- [2- (pyridazin-3-yl) thioethyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(pyrida2in-3-yl)thiopropyî]pipéridine-3-acétique 3 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 ~[34pyridazin-4-yi) propyl]pipéridine-3-acétique 82(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl) thiopropyl] piperidine acid 3-acetic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [34-pyridazin-4-yl] propyl] piperidine-3-acetic acid 82

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoliii-4-yl)propyl]-l-[4-(pyridazin-4-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridazin-4-yl) butyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[2-(pyridazin-4-yl)tbioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquolin-4-yl) propyl] -1- [2- (pyridazin-4-yl) butyl] piperidine acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-(pyridazm-4-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (pyridaz-4-yl) thiopropyl] piperidine acid 3-acetic acid

Acide (3R,4R)^-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-phényl-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) - [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1 - [3-phenyl-prop-2-ynyl] -piperidine-3 -acid -acetic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm^-yl)propyl]-l -[3-(2-fluoro-phényl)-prop-2-ynyl]-pipéridme-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1 - [3- (2-fluoro-phenyl) -prop-2- acid ynyl] -pipéridme-3-acetic acid

Acide (3R,4R>4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-fluoro-phényl)-prop-2-ynyl]-pipéridme-3-acétique(3R, 4R) 4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-fluoro-phenyl) prop-2 -acid] acid ynyl] -pipéridme-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-fluoro-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (4-fluoro-phenyl) -prop-2 -acid] acid ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-chlorophényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenyl) -prop-2-ynyl) -acid ] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-chloro-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-chlorophenyl) prop-2 -acid) ynyl] -piperidine-3-acetic acid

Acide (3R.4R)^[3-(R,S)-hydroxy-3-(6-méthoxyquiiiolin-4-yl)propyl]- l-[3-(4-chloro-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R4R) 3- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-phenyl) -prop-2-ynyl) acid ] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hvdroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-méthyl-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (2-methyl-phenyl) -prop-2 -acid] acid ynyl] -piperidine-3-acetic acid

Acide (3R,4R)^-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) - [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-methyl-phenyl) prop-2 -acid] acid ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(KS)-hydroxy-3-(6-méthoxyquinolin^-yl)propyl]-l-[3-(4-méthyl-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (KS) -hydroxy-3- (6-methoxyquinolin-1-yl) propyl] -1- [3- (4-methyl-phenyl) -prop-2-ynyl] acid piperidine-3-acetic acid

Acide (3R_4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-trifluoro-méthyl-phény!)-prop-2-\Tiyl]-pipéridinc-3-acétique(3R_4R) -4- [3- (RS) -Hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethyl-phenyl) prop-2 -acid] \ Tiyl] -pipéridinc-3-acetic acid

Acide (3R.4R)-4-[3-(R.S)-hydroxy-3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[3-(3-trifluoro-méthyl-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3-4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenyl) prop) -2-ynyl] -piperidine-3-acetic acid

Acide (3Rt4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-trifluoro-méthyl-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3Rt4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethyl-phenyl) -prop-2 -acid) ynyl] -piperidine-3-acetic acid

Acide (3R.4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin^-yl)propyl]-1 -[3-(2-méthoxy-phénvl)-prop-2-ynyl]-pipéridine-3-acétique(3-4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-1-yl) propyl] -1- [3- (2-methoxy-phenyl) prop-2- (4R) -R ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[3-(3-méthoxy-phényl)-prop-2-ynyl]-pipéridine-3-acétique 120 22 83(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinin-4-yl) propyl] -1 - [3- (3-methoxy-phenyl) -prop-2 -acid) -ynyl] -piperidine-3-acetic 120 22 83

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquiiiolin-4-yl)propyl]-l -[3-(4-méthoxy-phényi)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxy-phenyl) prop-2-acid) ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3,4-difluoro-phényl>prcp-2-ynyl]-pipéridine-3-acétique 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-niéthoxyquinolin-4-yl)prOpyl]-l-[3-(2,4-difluoro-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4-difluoro-phenyl) prcp- 2-ynyl] -piperidine-3-acetic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-difluoro-phenyl) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3,4-dichloro-phényl)-prop-2-ynyl]-pipàidine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4-dichloro-phenyl) prop) acid -2-ynyl] -pipàidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,3-dichloro-io phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichloro-10-phenyl) - prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolm-4-yl)propyl]-1 -[3-(2,4-dichloro-phényl)-prop-2-ynyl]-pipâidine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyqumol-4-yl) propyl] -1- [3- (2,4-dichloro-phenyl) prop) acid -2-ynyl] -pipâidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yi)propyl]-l-[3-(2,4,6-trichlorc>-phényl)-prop-2-ynyl]-pipéridine-3-acétique 15 Acide (3R,4R)-4-[3-(R,S>-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-l-[3-(3,5-dichloro-phényi)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trichloro) -phenyl) -acid ) -prop-2-ynyl] -piperidine-3-acetic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1 - [3- (3,5-dichloro-phenyl) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-mëthoxyquinolin-4-yl)propyl]-l -[3-(4-chIoro-3-fluoro-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3-fluoro-phenyl) acid) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3~(3-chloro-4-2 0 fluoro-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3 - (3-chloro-4-fluorophenyl) -acrylic acid; phenyl) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-(2-chloro-4-fluoro-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (2-chloro-4-fluoro-phenyl) acid) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydrox5?-3-(6-méihoxyqu)iiolm-4-yl)propyl]-l-[3-(3-chloro-5-fluoro-phényl)-prop-2-ynyl]-pipéridine-3-acétique 2 5 Acide (3R,4R)-4-[3“(R,S)4iydroxy-3-(6-mé!hoxyquinolin-4-yl)propyl]-1 -[3-(4-chloro-2- fluoro-phényl)-prop-2-ynyI]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Hydrox5 -3- (6-methyloxy) iolol-4-yl) propyl] -1- [3- (3-chloro-5-fluoro) -acid phenyl) -prop-2-ynyl] -piperidine-3-acetic acid (3R, 4R) -4- [3 - (R, S)) 4-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-2-fluoro-phenyl) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-fluoro-4-méthyl-phényi)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-4-methyl-phenyl) acid) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(4-chloro-3- 3 o trifluorométhyl-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (4-chloro-3-yl) trifluoromethyl) acid, phenyl) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-niéthoxyquinoiin-4-yl)propyl]- l-[3-(2-chloro-4-trifluorométhyl-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4-trifluoromethyl-phenyl) acid) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)^-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-chloro-5-trifluorométhyl-phényl)-prop-2-ynyl]-pipéridine-3-acétique 3 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(5-chioro-2-méthoxy-phényî)-prop-2-ynyl]-pipéridine-3-acétique 120 22 84(3R, 4R) - [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (2-chloro-5-trifluoromethyl-phenyl) - acid prop-2-ynyl] -piperidine-3-acetic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-Chioro-2-methoxy-phenyl) -prop-2-ynyl] -piperidine-3-acetic acid 120 22 84

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl3-l-[3-(3,5-bis-trifluoro-méthyl-phényl)-prop-2-ynyl]-pipéridme-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-bis-trifluoromethyl) phenyl) -acrylic acid ) -prop-2-ynyl] -pipéridme-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-l-[3-(355-diinéthyl-phényl)-prop-2-ynyl]-pipéridme-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (355-diinyl-phenyl) -prop-2) -acid ynyl] -pipéridme-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin4-yl)propyl]-l -[3-(2,4-dichloro-6-méthyl-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-dichloro-6-methyl-phenyl) acid) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(tbien-2-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (tbien-2-yl) prop-2) -acid ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[3-(5-chloro-thien-2-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chloro-thien-2-yl) acid) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-niéthoxyquiiiolin-4-yl)propyl]-1 -[3-(3-chloro-thien-2-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-thien-2-yl) acid) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl3-1 -[3-(5-méthyl-thien-2-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquolin-4-yl) propyl] -1 - [3- (5-methylthien-2-yl) - acid prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-méthyl-thien-2-yl)-prop-2-ynyi]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylthien-2-yl) acid) -prop-2-ynyi] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(thien-3-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop-2) -acid ynyl] -piperidine-3-acetic acid

Acide (3R,4R)4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-( 1 -méthyl-pyrrol- 2- yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) 4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methyl-pyrrol-2-yl) acid - prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R4R)-4-[3-(R,S)-hydroxy-3-{6-méthoxyquinoIin-4-yl)propyl]-1 -[3-( 1 -méthyl-pyrrol- 3- \’l)-prop-2-ynyl]-pipéridine-3-acétique(3R4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinin-4-yl) propyl] -1- [3- (1-methyl-pyrrol-3-yl)) acid -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3RAR)4-[3-(R,S)4iydroxy446-méthoxyquinoliii-4-yl)piOpyl]-1 -[3-(thiazol-2-yl)-prop-2-\Tiyl]-pipéridine-3-acétique(3RAR) 4- [3- (R, S) 4-Hydroxy-446-methoxyquinol-4-yl) pIpyl] -1- [3- (thiazol-2-yl) -prop-2-yl] -piperidine-3- acid acetic

Acide (3R,4R)4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyI]-1 -[3-(thiazol-4-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) 4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazol-4-yl) prop-2- acid) ynyl] -piperidine-3-acetic acid

Acide (3R.4R)-4-[3-(R,S)-bydroxy-3-(6-méthoxyquinolin4-yl)propyl]-1 -[3-(thiazol-5-yl)-prop-2-\"iylj-pipéridbie-3-acélique(3R, 4R) -4- [3- (R, S) -Bydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazol-5-yl) prop-2-) - acid "iylj-pipéridbie-3-acélique

Acide (3R4R)-A[3-(R,S)-hydroxy-3-(6-méthoxyquinolmA-yl)propyl]-1 -[3-( 1 -méthyl-imidazol-2-yl)-prop-2'ynyl]-pipéridine-3-acétique(3R4R) -A [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1 - [3- (1-methyl-imidazol-2-yl) prop-2 'acid ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-métho?cyquinolin-4-yl)propyl]-1 -[3-(3-méthyl-imidazol4-yl)-prop-2-ynyl]-pipéridme-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-metho-cyquinolin-4-yl) propyl] -1 - [3- (3-methyl-imidazol-4-yl) acid -prop-2-ynyl] -pipéridme-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl-p\Tazol-4-yl)-prop-2-ynyl]'-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl) p -azol) acid; 4-yl) -prop-2-ynyl] '- piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(oxazol-2-yl)-prop-2-ynyl]-pipéridine-3-acétique 120 22 85(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) prop-2) -acid -ynyl] -piperidine-3-acetic acid 120 22 85

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-(oxazol-4-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxy-iminolin-4-yl) -propyl] -1 - [3- (oxazol-4-yl) -prop-2 -acid) ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-{6-méthoxyquinolin-4-yl)propyl]-1 -[3-(oxaziol-5-yl)-prop-2-ynyl]-pipéridine-3-acétique 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(pyridin-2-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxaziol-5-yl) prop-2) -acid -ynyl] -piperidine-3-acetic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquolin-4-yl) propyl] -1- [3- pyridin-2-yl) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridm-3-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) prop-2) -acid ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin^4-yl)propyl]-1 -[3-(pyridin-4-yl)-10 prop-2-ynyi]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl) -propionic acid; 2-ynyi] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl3-l-[3-(pyrimidin-2-yl)-prop-2-ynyî]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) prop-2- acid) ynyî] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-4-yl)-prqp-2-ynyl]-pipéridine-3-acétique 15 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-5-yl)··prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-4-yl) -prop-2) acid -ynyl] -piperidine-3-acetic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- pyrimidin-5-yl) ·· prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yi)propyl]-1 -[3-(pyrazin-2-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) prop-2) -acid ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]- l-[3-(pyridazin-3-yl)-20 prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxy-iminolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) -propyl) -propionic acid; 2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(pyridazin-4-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (pyridazin-4-yl) prop-2) -acid ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-<R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-phœylpropèn-2-yl]pipéridine-3-acétique 2 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-phénylbutèn-3- yl]pipéridine-3-acétique(3R, 4R) -4- [3- <R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylpropen-2-yl] piperidine-3-acetic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4-phenylbuten-3-yl] piperidine-3-acid -acetic

Acide (3R,4R)A-[3-(R,S>fluoro-3-(6-méthoxyquinolin-4-yl)propyl]4-[3-phénylpropyl]pipéridine-3-acétique(3R, 4R) -A- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -4- [3-phenylpropyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinoIin-4-yl)propyl]-l-[4-phénylbutyl] 3 0 pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinin-4-yl) propyl] -1- [4-phenylbutyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-fluorophényl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenyl) propyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-métlioxyqumolin-4-yl)propyl]-1 -[4-(2~fluorophényl)butyl]pipéridine-3-acétique 3 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinoiin-4-yl)propyl]-1 -[3-(3-fluorophényl) propyl]pipéridine-3-acétique 86(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methylquinolin-4-yl) propyl] -1- [4- (2-fluorophenyl) butyl] piperidine-3- acid Acetic acid (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) propyl] piperidine -3-acetic 86

Acide (3R,4R)-4-[3-<R,S)-fluOTO-3-(6-méthoxyqiimoIin-4-yl)propyl]-l-[4-(3-fluoiOphényl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- <R, S) -FluO- (3- (6-methoxyquinyl-4-yl) propyl] -1- [4- (3-fluoro-phenyl) butyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(RS)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(4-fluorophényl)propyljpipéridine-3-acétique(3R, 4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (4-fluorophenyl) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(4-fluorophényl)hutyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-fluorophenyl) hutyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R,S)-iluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(2,3-difluoro-phényl)propyl]pipéridme-3-acétique(3R, 4R) -4- [3- (R, S) -Lluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (2,3-difluoro-phenyl) propyl] acid pipéridme-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-inéthoxyquinolin-4-yl)propyl]-1 -[4-(2,3-difluorophényl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,3-difluorophenyl) butyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[3-(2,6-difluoro-phényl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinin-4-yl) propyl] -1- [3- (2,6-difluoro-phenyl) propyl] acid piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(2,6-difluoro-phényl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-difluorophenyl) butyl] acid piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-niéthoxyquinolm-4-yl)propyl]-1 -[3-(2-chlorophényl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxy-4-yl) propyl] -1- [3- (2-chlorophenyl) propyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R.S)-fluorc>-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(2-chlorophényl)butyl]pipéridme-3-acétique(3R, 4R) -4- [3- (RS) -Fluoro) -3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-chlorophenyl) butyl] piperidin-3-acetic acid

Acide (3R,4R)^-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-chlorophényl)propyl]pipéridine-3-acétique(3R, 4R) 1- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenyl) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(3-chlorophényl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-chlorophenyl) butyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinotin-4-yl)propyl]-1 -[3-(4-chlorophényl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinotin-4-yl) propyl] -1- [3- (4-chlorophenyl) propyl] piperidine-3- acid acetic

Acide (3R,4R)^-[3-(R,S)-iluoro-3-(6-méthoxyquinolm-4-\'l)propyl]-1 -[4-(4-chlorophényl)butyl]pipéridine-3-acétique(3R, 4R) 1- [3- (R, S) -Lluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [4- (4-chlorophenyl) butyl] piperidine-3-acid -acetic

Acide (3R-4R)^l-[3-(KS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,3-dichloro-phényl)propy]]pipéridine-3-acétique(3R-4R) 1- [3- (KS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichloro-phenyl) propyl] piperidine acid -3-acetic acid

Acide (3R.4R)-4-[3-(R_S)-fluoro-3-(6-méthoxyquinolin-4->ï)propyl]-1 -[4-(2.3-dichloro-phényl)butyl]pipéridine-3 -acétique(3R4R) -4- [3- (R-S) -Fluoro-3- (6-methoxyquinolin-4- (1H) propyl] -1- [4- (2,3-dichloro-phenyl) butyl] piperidine-3-acid -acetic

Acide (3R.4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,6-dichlorophényl)propyl]pipéridine-3-acétique(3-4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-dichlorophenyl) propyl] piperidine acid 3-acetic acid

Acide (3R.4R)-4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(2,6-dichloro-phényl)butyl]pipéridine-3-acétique ,(3R4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-dichloro-phenyl) butyl] piperidine-acid 3-acetic,

Acide (3R4R)-4-[3-(KS)-fluoro-3-(6-méthoxyquinoiin-i-\'l)propyl]-1 -[3-(2-méthylphénvl)propyl]pipéridine-3-acétique x 1?0 2ÿ 87(3R4R) -4- [3- (KS) -Fluoro-3- (6-methoxyquinolin-1-yl) propyl] -1- [3- (2-methylphenyl) propyl] piperidine-3-acetic acid x 1? 0 2ÿ 87

Acide (3R,4R}4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l -[4-(2-méthylphényl)butyl]pipéridine-3-acétique(3R, 4R) 4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-methylphenyl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinoIin-4-yl)propyl]-l -[5-(2-méthylphényl)pentyl]pipéridine-3-acétique 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-inélhoxyquinolin-4-yi)propyl]-1 -[3-(3-méthylphényl) propyi]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinin-4-yl) propyl] -1 - [5- (2-methylphenyl) pentyl] piperidine-3- acid Acetic acid (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenyl) propyl] piperidine 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-{luoro3-(6-méÜioxyqumolin-4-yl)propyl]-l-[4-(3-méthylphényl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) - (Luoro) - (6-methyloxy-4-yl) propyl] -1- [4- (3-methylphenyl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-l -[3-(4-méthylphényl) 10 propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (4-methylphenyl) propyl] piperidine-3 acid -acetic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méth.oxyquinolin-4-yl)propyl]-l-[4-(4-méthylphényl)butyl]pipàidine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-methylphenyl) butyl] pipaladine- 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumoliii^l~yl)propyl]-l-[3-(2-méthoxyphényl)propyl]pipéridine-3-acétique 15 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méü^oxyqumolin-4-yl)propyl]'l-[4-(2-méîhoxyphényl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxy-iminol-1-yl) -propyl] -1- [3- (2-methoxyphenyl) -propyl] -piperidine-3- acid Acetic acid (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methyloxy) iminolin-4-yl) propyl] 1- [4- (2-methoxyphenyl) butyl] piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthoxyphényl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenyl) propyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méüioxyquinoliii-4-yl)propyl]-l-[4-(3-méthoxyphényl)20 butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methyloxyquinolin-4-yl) propyl] -1- [4- (3-methoxyphenyl) butyl] piperidine-3-acid -acetic

Acide (3R,4R)^-[3<R,S)-fluoro-3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[3-{4-méthoxyphényl)propyl]pipéridine-3-acétique(3R, 4R) 1- [3 R, S) -Fluoro-3- (6-methoxyquinin-4-yl) propyl] -1- [3- (4-methoxyphenyl) propyl] piperidine-3-acetic acid

Acide (3R,4R>4-[3-(R,S)-fluoro-3-(6-inéthoxyquinolm-4-yl)propyl]-l-[4-(4-méthoxyphényl)butyl)pipéridine-3-acétique 2 5 Acide (3R,4R)-4-[3-<R,S)-fluorc>-3-(6-niéthoxyquinoIin-4-yl)propyl]-l-[3-(2-trifluorométhyl- phényl)propyl]pipéridine-3-acétique(3R, 4R) 4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [4- (4-methoxyphenyl) butyl) piperidine-3-acetic acid (3R, 4R) -4- [3- <R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethylphenyl) propyl) -acid ] piperidin-3-acetic acid

Acide (3R,4R>4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(2-trifluorométhyl-phényl)butyl]pipéridine-3~acétique(3R, 4R) 4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-trifluoromethyl-phenyl) butyl] piperidine-3-acid ~ acetic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-trifluorométhyl-30 phényl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenyl) propyl] piperidine acid -3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yi)propyl]- l-[4-(3-trifluorométhyl-phényl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-trifluoromethyl-phenyl) butyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-trifluorométhyl-phényl)propyl]pipéridme-3-acétique 3 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(4-trifluorométhyl- phényl)butyl]pipéridine-3-acétique ’?0 2ί' - 88(3R, 4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethyl-phenyl) propyl] piperidin-3- acid Acetic acid (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-trifluoromethylphenyl) butyl) ] piperidine-3-acetic acid '? 0 2ί' - 88

Acide (3R,4R)-4-[3-(R,S)-iluoro-3-(6-inéthoxyquino!in-4-yl)propyl]-1 -[2-phénylthio-étiiyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Lluoro-3- (6-ethoxyquinino-4-yl) propyl] -1- [2-phenylthio-etiyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[ 3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-phénylthio-propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylthiopropyl] piperidine-3-acetic acid

Acide (3R,4R)-4-i3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yI)propyl]-1 -[2-(2-fluorophényl-thio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-fluorophenylthio) ethyl] piperidine-3 acid -acetic

Acide (3R,4R)-4-[ 3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-fluorophényl-thio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenylthio) propyl] piperidine acid 3-acetic acid

Acide (3R,4R)-4-i3-(R,S)-iluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3-fluorophényl-thio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Lluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluorophenylthio) ethyl] piperidine-3-acid -acetic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[3-(3-fluorophényl-thio)propyl]pipéricme-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenylthio) propyl] acid pipéricme-3-acetic acid

Acide (3R-4R)^-[ S-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(4-fluorophényl-tbio)éthyl]pipéridhe-3-acétique(3R-4R) 1- [S - (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-fluorophenyl-tbio) ethyl] piperid-3-acid -acetic

Acide (3R-4R)-4-‘ 3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-fluorophényl-thio)propyl]pipériGine-3-acétique(3R-4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenylthio) propyl] piperidinic acid; 3-acetic acid

Acide (3R,4R)^4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2,3-difluoro-phénylthio)éthyl]p4?éridine-3-acétique(3R, 4R) 4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-difluoro-phenylthio) ethyl] acid p4? éridine-3-acetic

Acide (3R,4R)-4-[ 3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,3-difluoro-phénylthio)propylpipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluoro-phenylthio) propylpiperidine) acid 3-acetic acid

Acide (3R,4R)-4-: 3-(R,S)-fluoro-3-(6-méthoxyquinolin^l-yl)propyl]-1 -[2-(2,6-difluoro-phénylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4-: 3- (R, S) -Fluoro-3- (6-methoxyquinolin-1-yl) propyl] -1- [2- (2,6-difluoro-phenylthio) ethyl] acid piperidin-3-acetic acid

Acide (3R,4R)-4-i ?-(R,S)-fluoro-3-(6-mé±oxyquinoIin-4-yl)propyl]-1 -[3-(2,6-difluoro-phénylthio)propylbipéridine-3-acétique(3R, 4R) -4-1- (R, S) -Fluoro-3- (6-methyloxyquinolin-4-yl) propyl] -1- [3- (2,6-difluoro-phenylthio) acid) propylbipéridine-3-acetic acid

Acide (3R,4R)-4-’?-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2-chlorophényl-thio)éthyl]pipéridr.e-3-acétique(3R, 4R) -4- [N- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-chlorophenylthio) ethyl] piperid] acid. e-3-acetic acid

Acide (3R-4R)^4-'?-(R,S)-iluoro-3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[3-(2-chlorophényl-thio)propyl]pipén—ie-3-acétique(3R-4R) -4- (R, S) -Lluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenylthio) propyl] acid Pipen-ie-3-acetic acid

Acide (3R.4R)-4-i3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)prqpyl]-l-[2-(3-chlorophényl-thio)éthyl]pipéridne-3-acétique(3R- (4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chlorophenylthio) ethyl] piperid-3-acid -acetic

Acide (3R,4R)-4-\;-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(3-chlorophényl-thio)propyl]pipéncine-3-acétique(3R, 4R) -4- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (3-chlorophenyl-thio) propyl] pipercinic acid; 3-acetic acid

Acide (3R.4R)-4-^?-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(4-chlorophényl-thio)éthyl]pipéridr-e-3-acétique(3R4R) -4- [N- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-chlorophenylthio) ethyl] piperid] acid e-3-acetic acid

Acide (3R,4R)-4- ?-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-chlorophényl-thio)propyl]pipéri±ne-3-acétique 120 2 2 89(3R, 4R) -4-? - (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenylthio) propyl] piperanic acid -3-acetic 120 2 2 89

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-métiioxyqumolin-4-yl)propyl]-l-[2-(2,3-dichlorc>-phénylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-dichloro) -phenylthio) ethyl acid ] piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumoim-4-yl)propyl]-l-[3-(2,3-dichloro-phénylthio)propyl]pipéridme-3-acétique 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-l-[2-(2J6-dichIoro-phénylthio)éîhyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquimmon-4-yl) propyl] -1- [3- (2,3-dichloro-phenylthio) propyl] acid piperidin-3-acetic acid (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [2- (2H-dichloro) -acrylic acid) phenylthio) éîhyl] piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méÜioxyquinolin-4-yl)prppyl]-l-[3-(2,6-dichloro-phénylthio)propyî]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methyloxyquinolin-4-yl) propyl] -1- [3- (2,6-dichloro-phenylthio) propyl] acid piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolm-4-yl)propyl]-1 -[2-(2-méthylphényl-io thio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyqumol-4-yl) propyl] -1- [2- (2-methylphenyl-10-thio) ethyl] piperidine acid -3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]- l-[3-(2-méthylphényl-thio)propyl]pipéridme-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (2-methylphenylthio) propyl] piperidinic acid; 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-l-[2-(3-méth.ylphényl-thio)éthyl3pipéridine-3-acéùque 15 Acide (3R,4R)-4-[3-(R,S)-iluoro-3-(6-mélhoxyquinolin-4-yl)propyl]-1 -[3-(3-méthylphén.yl- thio)prqpyl]pipâidme-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [2- (3-methylphenylthio) ethyl) piperidine-acid 3-Acetic acid (3R, 4R) -4- [3- (R, S) -Lluoro-3- (6-methoxyphenolin-4-yl) propyl] -1- [3- (3-methylphenyl) ethyl) thio) prqpyl] pipâidme-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méÛioxyquinolin-4-yl)propyl]-1 -[2-(4-méthylphényl-1hio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methyloxyquinolin-4-yl) propyl] -1- [2- (4-methylphenyl-1H) -ethyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-métfaoxyquinolin-4-yl)propyl]-1 -[3-(4-méthylphényl-20 tbio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-metfaoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenyl) -bio] propyl] piperidine acid -3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-inéthoxyquinolin-4-yl)propyI]-1 -[2-(2-trifluorométhyl-phénylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-trifluoromethyl-phenylthio) ethyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2-trifluiOméthyl-phénylthio)propyl]pipéridine-3-acéùque 2 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3-trifluorométhyl- phénylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethyl-phenylthio) propyl] piperidine-acid 3-Acetic acid (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethylphenylthio) ) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin^-yl)propyl]-1 -[3-(3-triflurométhyl-phénylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-1-yl) propyl] -1- [3- (3-trifluromethyl-phenylthio) propyl] piperidine-3-acid -acetic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[2-(4-trifluoromé±yl-30 phénylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [2- (4-trifluoromethyl) phenylthio) ethyl acid ] piperidin-3-acetic acid

Acide (3R4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-triflurométhyl-phénylthio)propyl]pÎpéridine-3-acétique(3R4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluromethyl-phenylthio) propyl] -piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propylj-1 -[2-(2-méthoxyphénylthio)éthyl]pipéridine-3 -acétique 3 5 Acide (3R4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propylj-1 -[3-(2-méthoxyphényl thio)propyl3pipéridine-3-acétique 90(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methoxyphenylthio) ethyl] piperidine-3-acetic acid (3R4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenylthio) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-{6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3-méthoxyphényl-tbio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methoxyphenyl-tbio) ethyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S>-fluoro-3-(6-méthoxyqumoiin-4-yl)propyl]-1 -[3-(3-méthoxyphényl-tbio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxy-4-yl) propyl] -1- [3- (3-methoxyphenyl-tbio) propyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-<6-méthoxyquinolin-4-yl)propyl]-l-[2-<4-méthoxyphényl-thio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methoxyphenylthio) ethyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(4-méthoxyphényl-ihio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenyl) halo) propyl] piperidine acid; 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[cyclopropylméthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [cyclopropylmethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin^4-yl)propyl]-1 -[2-(cyclopropyl)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopropyl) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-l -[cyclobutybnéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxy-iminolin-4-yl) propyl] -1 - [cyclobutybethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R!S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(cyclobutyl)éthyl]ipéridine-3-acétique(3R, 4R) -4- [3- (R1 S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclobutyl) ethyl] iperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[cyclopentyhnéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [cyclopentyhnethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(cyclopentyl)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentyl) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[cyclohexylméthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [cyclohexylmethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[2-(cyclohexyl)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(cyclopropylthio)é±yl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopropylthio) ethyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(cyclopropylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopropylthio) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R.S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(cyclobutylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclobutylthio) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R.S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-{cyclobutylthio-propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- {cyclobutylthio-propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R.S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[2-(cyclopentylthio)éthyl]pipéridine-3-acétic(be(3R, 4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-3-acetic acid (be

Acide (3R,4R)-4-[3-(KS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(cyclopentylthio)propyl]pipéridine-3-acétique 120 2 2 91(3R, 4R) -4- [3- (KS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopentylthio) propyl] piperidine-3-acetic acid 120 2 2 91

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[2-(cyclohexylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méihoxyquiQolin-4-yl)propyl]-l-[3-(cyclohexylthio)propyl]pipéridine-3-acétique 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinoIin-4-yl)propyl]-l-[2-méthylthioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methyloxyquiolin-4-yl) propyl] -1- [3- (cyclohexylthio) propyl] piperidine-3-acetic acid (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinin-4-yl) propyl] -1- [2-methylthioethyl] piperidine-3-acetic acid

Acide (3R,4R)4-[3-(R,S)-fluorc>-3-(6-méthoxyqumolm-4-yl)propyl]-l-[3-inéthylthiopropyljpipéridine-3-acétique(3R, 4R) 4- [3- (R, S) -Fluoro) -3- (6-methoxyqumol-4-yl) propyl] -1- [3-ethylthiopropyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(RîS)-fluOTO-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-éthylÎhioéthyl]îo pipéridine-3-acétique(3R, 4R) -4- [3- (R 1 S) -FluO-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-ethyl-hydroxyethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-iluorc>-3-(6-méthûxyquinolin-4-yl)propyl]-1 -[3-éthyltbiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Lucu) -3- (6-methylquinolin-4-yl) propyl] -1- [3-ethyltbiopropyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-inéthoxyquinolin-4-yl)propyl]-l-[2-(n-propylÜîio)étbyl]pipéridine-3-acétique 15 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(n-propylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (n-propyl-ethyl) ethyl] piperidine-3- acid Acetic acid (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (n-propylthio) propyl] piperidine 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(n-butylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (n-butylthio) ethyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yi)propyl]-1 -[3-(n-butylthio)propyl]20 pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (n-butylthio) propyl] piperidine-3 acid -acetic

Acide (3R,4R)^-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(thien-2-yl)propyl]pipéridine-3-acétique(3R, 4R) 1- [3- (R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (thien-2-yl) propyl] piperidine-3 acid -acetic

Acide (3R,4R)-4-[3-(R,S)-iluoro-3-(6-métboxyquinolin-4-yl)propyl]-l-[4-(tbien-2-yl)butyl]pipéridine-3-acétique 2 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[2-(thien-2-yl)thio- éthyl]pipéridine'3-acétique(3R, 4R) -4- [3- (R, S) -Lluoro-3- (6-metboxyquinolin-4-yl) propyl] -1- (4- (tert-2-yl) butyl] piperidine-acid 3-acetic acid (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyqumolin-4-yl) propyl] -1- [2- (thien-2-yl) ) thioethylpiperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 - [3-(thien-2 -yl)thio-propyljpipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) thio-propyl] piperidine acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(5-chloro-thien-2-30 yl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (5-chloro-thien-2-yl) -acid ) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(5-chloro-thien-2-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [4- (5-chloro-thien-2-yl) acid butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 ^-(S^hloro-thien^-ylXhioéthy^pipéridine-S-acétique 3 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(5-chloro-thien-2- yl)thiopropyl]pipéridine-3-acétique 120 ? 2 92(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1H- (5H-chloro-thien-1-yl) ethyl) piperidine-S acid Acetic acid (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chloro-thien) 2-yl) thiopropyl] piperidine-3-acetic acid 120-292

Acide (3R,4R)-4-[3-(R,S)-fluor(>-3-(6-méthoxyquinolm-4-yl)propyI]-l-[3-(3-chloro-thien-2-yl)prqpyl]pipéridme-3-acétique(3R, 4R) -4- [3- (R, S) -Fluor (> - 3- (6-methoxyquinol-4-yl) propyl] -1- [3- (3-chloro-thien-2-yl) -acrylic acid yl) prqpyl] pipéridme-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluon>3-(6-méthoxyquinoIin-4-yl)piOpyl]-1 -[4-(3-chloro-thien-2-yl)buîyl]pipéridine-3-acétique 5 Acide (3R,4R)-4-[3-<R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3-chloro-thien-2- yl)îhioéihyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluon> 3- (6-methoxyquinin-4-yl) p-pyl] -1 - [4- (3-chloro-thien-2-yl) acid [3 R, 4 R) -4- [3- (R) S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3- (3R, 4R) -4- [3- (R) S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- chloro-thien-2-yl) thiohexyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-chloro-thien-2-yl)tMopropyl]pipéridirie-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-chloro-thien-2-yl) acid tMopropyl] pipéridirie-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-niéthoxyquinolin-4-yl)propyl]-l-[3-(5-méthyl -thien-2-10 yl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-methyl-thien-2-10 yl) -acid ) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquiiiolm-4-yl)propyl]-l-[4-(5-méthyl -thien-2-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxy-4-quinol-4-yl) propyl] -1- [4- (5-methyl-thien-2-yl) -acid butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(5-méthyl -thien-2-yl)thioéthyl]pipéridine-3-acétique 1 s Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-niéîhoxyquinoliii-4-yl)propyl]-1 -[3-(5-métby] -thien-2- yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (5-methylthien-2-yl) acid) thioethyl] piperidine-3-acetic acid 1S (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-nitroxyquinolin-4-yl) propyl] -1- [3- -metby] -thien-2-yl) thiopropyl] piperidine-3-acetic acid

Acide (3R,4R)4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl -tbien-2-yl)propyl]pipéridine-3-acétique(3R, 4R) 4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-tert-2-yl) propyl] acid ] piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(3-inétbyl -thien-2-20 yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-butyl-thien-2-yl) -yl ) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-niéthoxyquinolm-4-yl)propyl]-l-[2-(3-inéthyl -thien-2-yl)thioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxy-4-yl) propyl] -1- [2- (3-ethyl-thien-2-yl)) acid thioethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]- l-[3-(3-métiiyl -thien-2-yl)thiopropyl]pipéridine-3-acétique 2 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(thien-3-yl)propyl] pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-thien-2-yl) acid thiopropyl] piperidine-3-acetic acid (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- 3-yl) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(thien-3-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-3-yl) butyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]- l-[2-(thien-3-yl)thio-30 éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [2- (thien-3-yl) thio-ethyl) acid ] piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(thien-3-yl)thio-propyl]pipéridine-3 -acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (thien-3-yl) thio-propyl] acid Piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[3-(fur-2-yl)propyl]pipéridine-3-acétique ' 3 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[4-(fur-2-yl)butyl] pipéridine-3-acétique T2022 93(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinin-4-yl) propyl] -1- [3- (fur-2-yl) propyl] piperidine-acid 3-acetic acid (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [4- (fur-2- yl) butyl] piperidine-3-acetic acid T2022 93

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquiiiolin-4-yl)propyl]-l-[2-(fur-2-yl)thioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (fur-2-yl) thioethyl] piperidine acid; 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-(fur-2-yl)thio-propyl]pipéridine-3-acétique 5 Acide (3R,4R)-4-[3-(R,S)-iluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(fur-3-yl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (fur-2-yl) thio-propyl] acid Piperidine-3-acetic acid (3R, 4R) -4- [3- (R, S) -Lluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (fur-3- yl) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-iluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(fur-3-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Lluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (fur-3-yl) butyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[2-(fur-3-yl)thioéthyl]îo pipéridine-3-acéüque(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [2- (fur-3-yl) thioethyl] piperidine acid -3-acéüque

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(fur-3-yl)thio-propyl]pipéridme-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (fur-3-yl) thio-propyl] acid pipéridme-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-( 1 -méfliyl-pynol-2-yl)propyl]pipéridine-3-acétique ï 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-( 1 -méthyl-pyrrol-2- yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-mefliyl-pynol-2-yl) acid) propyl] piperidin-3-acetic acid (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1) methyl-pyrrol-2-yl) butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l -[2-(l -méthyl-pyrrol-2-yl)thioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (1-methyl-pyrrol-2-yl) acid thioethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-( 1 -méthyl-pyrrol-2·20 yl)thiopropyI]pipéridme-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1 - [3- (1-methyl-pyrrol-2-yl) -acid ) thiopropyI] pipéridme-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-( 1 -méthyl-pyrrol-2-yl)propyl]pipéridine-3~acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (1-methyl-pyrrol-2-yl) acid propyl] piperidine-3-acetic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l -[4-(l -méthyl-pyrrol-3yl)butyl]pipéridine-3-acéüque 2 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(l -méthyl-pyirol-3 yl)thioéthy 1 Jpipéridine-3 -acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1-methyl-pyrrol-3-yl) butyl] acid Piperidine-3-acetic acid (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1-methyl) -pyirol-3-yl) thioethyl-3-piperidine-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-( 1 -méthyl-pyrrol-3yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methyl-pyrrol-3-yl) thiopropyl] acid piperidin-3-acetic acid

Acide (3R,4R) -4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3 -(thiazol-2-yl) 30 propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1 - [3 - (thiazol-2-yl) propyl] piperidine acid -3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(thiazol-2-yl)butyljpipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [4- (thiazol-2-yl) butyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(thiazol-2-yl)thio-éthyl]pipéridine-3-acétique 3 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propylj-1 -[3-(thiazol-2-yl)thio- propyl]pipéridine-3-acétique ’?022 94(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thiazol-2-yl) thio-ethyl] acid Piperidine-3-acetic acid (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazol-2- yl) thio-propyl] piperidine-3-acetic acid 022 94

Acide (3R,4R)-4-[3 -(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-( 1 -méthyl-imidazol-2-yl)prOpyl]pipéridme-3-acétique(3R, 4R) -4- [3 - (R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1 - [3- (1-methylimidazol-2-yl) acid propyl] pipéridme-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-niéthoxyqumolm-4-yl)propyl]-1 -[4-( 1 -méthyl-imidazol-2-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxy-4-yl) propyl] -1 - [4- (1-methyl-imidazol-2-yl) acid butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoiO-3-(6-méîhoxyquinolin-4-yl)propyl]-1 -[2-( 1 -méthyl-imidazol-2-yl)tbioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -FluoroO-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (1-methylimidazol-2-yl) acid tbioéthyl] piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin.-4-yl)propyl]-1 - [3 -( 1 -méthyl-imidazol-2-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3 - (1-methyl-imidazol-2-yl) ) thiopropyl] piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-inéthoxyquiiiolin-4-yl)propyl]-1 -[3-(3-méthyl-imidazol-4-yl)propyl]pipéridme-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-ethoxyquinolin-4-yl) propyl] -1 - [3- (3-methyl-imidazol-4-yl) acid propyl] pipéridme-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(3-méthyl-imidazol-4-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [4- (3-methyl-imidazol-4-yl) acid butyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fiuoro-3-(6-méthoxyquinolin-4-yl)propyl]-l -[2-(3-méthyl-imidazol-4-yl)thioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methyl-imidazol-4-yl) acid) thioethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3 -(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl-imidazol-4-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3 - (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-methyl-imidazol-4-yl) acid thiopropyl] piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl-pyrazol4-yl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-pyrazol-4-yl) propyl] acid piperidin-3-acetic acid

Acide (3R,4R>4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[4-(3-méthyl-pyrazol4-yl)butyl]pipéridine-3-acétique(3R, 4R) 4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [4- (3-methyl-pyrazol-4-yl) butyl] piperidine acid -3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-inéthoxyquinolin-4-yl)propyl]-1 -[2-(3-méthyl-pyrazol4-yl)thioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methyl-pyrazol-4-yl) thioethyl] acid piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(3-méthyl-pyrazol4-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (3-methyl-pyrazol-4-yl) thiopropyl] acid piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-inéthoxyquiiiolin-4-yl)propyl]-1 -[3-(oxazol-2-yl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-ethoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) propyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[4-(oxazol-2-yl)but) l]pipéridine-3-acéiique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methyloxyquinolin-4-yl) propyl] -1- [4- (oxazol-2-yl) butyl) acid) t] piperidine-3-acéiique

Acide (3R4R)^l-[3-ÇRS)-fluoro-3-(6-méthoxyquinoLLn-4-yl)propyl]-1 -[2-(oxazol-2-yl)thioéthyl]pipéridine-3-acétique(3R4R) 1- [3-CRS) -Fluoro-3- (6-methoxyquinyl-4-yl) propyl] -1- [2- (oxazol-2-yl) thioethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(oxazol-2-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) thiopropyl] piperidine acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridin-2-yl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) propyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-vl)propyl]-1 -[4-(pyridin-2-yl)butyl]pipéridine-3-acétique 95(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-2-yl) butyl] piperidine-acid 3-acetic 95

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)prapyl]-l -[2-(pyridin-2-yl)tHoéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) -propyl] -1 - [2- (pyridin-2-yl) -ethyl] piperidine-acid 3-acetic acid

Acide (3RXR)-4-[3-(R,S)-fluoio-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-(pyridin-2-yl)thiopropyljpipéridine-3-acétique 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(pyridin-3-yl)propyl]pipéridine-3-acétique(3RXR) -4- [3- (R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (pyridin-2-yl) thiopropyl] piperidine-3-acetic acid (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl) propyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méÜioxyquinolin-4-yl)propyI]-l-[4-(pyridin-3-yl)butylJpipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methyloxyquinolin-4-yl) propyl] -1- (4- (pyridin-3-yl) butyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[2-(pyridin-3-yl) 10 thioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [2- (pyridin-3-yl) thioethyl] piperidine acid -3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-iluoro-3-(6-méthoxyqumolm-4-yl)propyl]-l-[3-(pyridm-3-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Lluoro-3- (6-methoxyqumol-4-yl) propyl] -1- [3- (pyrid-3-yl) thiopropyl] piperidine acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4~yl)propyl]-l-[3-(pyridin-4-yl)propyl]pipéridine-3-acétique 15 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(pyridin-4-yl)butylJpipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (pyridin-4-yl) propyl] piperidine acid 3-acetic acid (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-4-yl) butylJpipéridine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumoIin-4-yl)propyl]-1 -[5-(pyridin-4-yl)penlyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxy-quinolin-4-yl) propyl] -1 - [5- (pyridin-4-yl) penyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[2-(pyridin-4-yl) 2 0 thioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinin-4-yl) propyl] -1- [2- (pyridin-4-yl) thioethyl] acid piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méihoxyquinolb-4-y!)propyî]-î-[3-(pyridm-4-yl)thiopropyljpipéridine-3 -acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolb-4-yl) propyl] -1- [3- (pyrid-4-yl) thiopropyl] piperidine-3-acid -acetic

Acide (3R,4R)-4-[3-(R5S)-fluoro-3-(6-méthoxyquinolin-4-yl)prcp3'l]-1 -[3-fcyrunidin-2-yl)propyl]pipéridine-3-acétique 2 5 Acide (3R54R)-4-[3-(R,S)-fluoro-3-(6-méîboxyquinoIin-4-yi)propyl]-1 -[4-(pyrimidin-2-yl) butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R5S) -Fluoro-3- (6-methoxyquinolin-4-yl) prcp3'l] -1- [3-fcyrunidin-2-yl) propyl] piperidine-3-acid Acetic acid (3R54R) -4- [3- (R, S) -fluoro-3- (6-methylbenzylquin-4-yl) propyl] -1- [4- (pyrimidin-2-yl) butyl] piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyrimidin-2-yl)thioéihyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidin-2-yl) thioheyl] piperidine acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méihoxyquinolin-4-yl)propyi]- l-[3-(pyrimidin-2-yl)30 thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) thiopropyl] piperidine acid -3-acetic acid

Acide (3R,4R)^-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-l -[3-(pyrimidin-4-yl)propyl]pipéridine-3-acétique(3R, 4R) 1- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (pyrimidin-4-yl) propyl] piperidine-3 acid -acetic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(pyrimidm-4-yl)butyl]pipéridine-3-acétique 3 5 Acide (3R,4R)-4-(3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyrimidin-4-yl) thioéthyÎ]pipéridine-3-acétique 120 2 2 96(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidin-4-yl) butyl] piperidine acid 3-acetic acid (3R, 4R) -4- (3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidin-4-yl) ) thioethylpiperidine-3-acetic 120 2 2 96

Acide (3R,4R)-4-[3-{R,S)-fluoro-3-(6-méthoxyqumolm-4-yl)propyl]-1 -[3-(pyrimidin-4-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyqumol-4-yl) propyl] -1- [3- (pyrimidin-4-yl) thiopropyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(pyriinidin-5-yl)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (pyriinidin-5-yl) propyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(pyrimidin-5-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidin-5-yl) butyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[2-(pyrimidin-5-yl)tbioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [2- (pyrimidin-5-yl) butyl] piperidine acid 3-acetic acid

Acide (3R,4R)-4-[3-(RS)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-(pyrimidin-5-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (pyrimidin-5-yl) thiopropyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyra2in-2-yl)propyljpipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrain-2-yl) propyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(pyrazin-2-yl)butyl]pipéridine-3-acétique(3R, 4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrazin-2-yl) butyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-l-[2-(pyra2in -2-yl)thioétbyl]pipéridine-3-acétiquc(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [2- (pyrain-2-yl) thioetyl] piperidine acid 3-acétiquc

Acide (3R,4R)-4-[3-(R,S)-fluora 3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(pyra2m-2-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyra-2-yl) thiopropyl] piperidine-3-acid -acetic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridazin-3-yl)prqpyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) propyl] piperidine acid 3-acetic acid

Acide (3R,4R)^-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[4-(pyridazin-3-yl)butyl]pipéridine-3-acétique(3R, 4R) - [3- (R, S) -Fluoro-3- (6-methoxy-iminolin-4-yl) propyl] -1 - [4- (pyridazin-3-yl) butyl] -piperidine-3 -acid -acetic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[2-(pyridazin-3-yl)thioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methyloxyquinolin-4-yl) propyl] -1- [2- (pyridazin-3-yl) thioethyl] acid piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridazin-3-yl)thiopropyl]pipéridine~3 -acétique(3R, 4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) thiopropyl] piperidine acid ~ 3 - acetic

Acide (3R4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin^4-yl)propyl]-1 -[3-(pyridazin^4-yl)propyî]pipéridinc-3-acétiquc(3R4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4-yl) propyl] piperidin-3- acid acétiquc

Acide (3R.4R)-4-[3-(R.S)-fluoro-3-(6-méthoxyquinolin—l-yl)propyl]-1 -[4-(pyridazin-4-yl)butyl]pipéridine-3-acétique(3R4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-1-yl) propyl] -1- [4- (pyridazin-4-yl) butyl] piperidine-3- acid acetic

Acide (3R,4R)^4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyridazin-4-yl)thioéthyl]pipéridine-3-acétique(3R, 4R) 4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridazin-4-yl) thioethyl] piperidine acid; 3-acetic acid

Acide (3R,4R)-4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridazin-4-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4-yl) thiopropyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-phényl-prop-2-ynyl]-pipéridine-3-acétique 12 0 2 2 97(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenyl-prop-2-ynyl] -piperidine-acid 3-acetic acid 12 0 2 2 97

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-iluoro-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (2-fluoro-phenyl) prop-2 -acid] acid ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l -[3-(3-fluoro-phényl)-prop-2-ynyl]-pipéridine-3-acétique 5 Acide (3R,4R)-4-[3-(R,S)-fluorc>-3-(6-méthoxyqumoIin-4-yl)propyl]-l-[3-(4-fluoro-phényl)-prop-2-ynyl3-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-fluoro-phenyl) -prop-2 -acid] acid -ynyl] -piperidine-3-acetic acid (3R, 4R) -4- [3- (R, S) -Fluoro) -3- (6-methoxyquinin-4-yl) propyl] -1- [3- (4-fluoro-phenyl) -prop-2-ynyl3-piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3--(2-chloro-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3 - (2-chloro-phenyl) propyl] -acrylic acid; 2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-chloro-phényl)-10 prop-2-ynyl]-pipéridme-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-phenyl) -propionic acid; 2-ynyl] -pipéridme-3-acetic acid

Acide (3R,4R)-4-[3-{R,S)-fluoro-3-(6-niéthoxyqumolin-4-yl)propyl]-1 -[3-(4-chloro-phényI)-prop-2-ynyl]-pipàidine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxy-4-yl) -propyl] -1 - [3- (4-chlorophenyl) -prop-2 -acid) ynyl] -pipàidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méihoxyquinolin-4-yl)propyl]-l-[3-(2-méthyl-phényl)prop-2-ynyl]-pipéridine-3-acétique 15 Acide (3R,4R)-4-[3-(R,S)-fiuoro-3-(6-métboxyquinolin-4-yl)propyl]-1 '[3-(3-méthyl-phényl) prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methyloxyquinolin-4-yl) propyl] -1- [3- (2-methyl-phenyl) prop-2- acid [(3R, 4R) -4- [3- (R, S) -fluoro-3- (6-metboxyquinolin-4-yl) propyl] -1,3-acetic acid (3R, 4R) -3-acetic acid methyl-phenyl) prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-méthyl-phényl)prop-2-ynyl]-pipéridine-3-acétique(3R4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methyl-phenyl) prop-2-ynyl] acid piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-trifluorométhyl20 phényl)-prop-2-ynyl]-pipéridme-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethyl) phenyl) prop-2- acid ynyl] -pipéridme-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-trifluorométhylphényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenyl) -prop-2-ynyl) -acid ] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-iluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-trifluorométhylphényl)-prop-2-ynyl]-pipéridine-3-ac'Æüque 2 5 Acide (3R4R)-4-[3-(R,S)'fluoro-3-(6-méthoxyquinolin~4-yl)propyl]-1 -[3-(2-méthoxy- phényi)-prop-2-ynyl]-pipéridine-3-acélique(3R, 4R) -4- [3- (R, S) -Lluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenyl) -prop-2-ynyl) -acid ] -piperidine-3-acetic acid (3R4R) -4- [3- (R, S) 'fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2) -methoxy-phenyl) -prop-2-ynyl] -piperidine-3-acelic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthoxy-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-methoxy-phenyl) -prop-2 -acid] acid ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-méthoxy- 3 0 phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenyl) prop) acid -2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]- l-[3-(3,4-difluoro-phényl)-prop-2-ynyl3-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4-difluoro-phenyl) prop) acid -2-ynyl3-piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]~ 1 -[3-(2,4-difluoro-phényl)-prop-2-ynyl]-pipéridine-3-acétique 3 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3,4-dicbloro- phényl)-prop-2-ynyl]-pipéridine-3-acétique 120 22 98(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-difluoro-phenyl) prop) acid 2-ynyl] -piperidine-3-acetic acid (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [ 3- (3,4-dicblorophenyl) -prop-2-ynyl] -piperidine-3-acetic acid 120 22 98

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,3-dichloro-phényl)-prop-2-ynyl]-pipéridme-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (2,3-dichloro-phenyl) prop) acid -2-ynyl] -pipéridme-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqLimolin-4-yl)propyl]-l-[3-(2.4-dichloro-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxy-iminolin-4-yl) propyl] -1- [3- (2,4-dichlorophenyl) prop-2 -acid] acid ynyl] -piperidine-3-acetic acid

Acide(3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolm-4-yl)propyl]-l-[3-(2,4,6-trichloro- phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyqumol-4-yl) propyl] -1- [3- (2,4,6-trichlorophenyl) acid) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3,5-dichloro-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-dichloro-phenyl) prop) acid -2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-(4-chloro-3-fluoro-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (4-chloro-3-fluoro-phenyl) acid) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-iluoro-3-(6-méthoxyqumoiin-4-yl)propyl]-1 -[3-(3-chloro-4-fluoro-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Lluoro-3- (6-methoxy-4-yl) -propyl] -1- [3- (3-chloro-4-fluoro-phenyl) acid) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqLimolin-4-yl)propyl]-1 -[3-(2-chIoro-4-fluoro-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxy-iminolin-4-yl) propyl] -1- [3- (2-chloro-4-fluoro-phenyl) acid) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R_4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-chloro-5-fluoro-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R_4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-chloro-5-fluoro-phenyl) -prop acid -2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)^4-[3-(R,S)-fluoro- 3-(6-méihoxyquinolin-4-yl)propyl]-1 -[3-(4-chloro-2-fluoro-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) 4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-2-fluoro-phenyl) acid) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[3-(3-fluoro-4-méthyl-phényl)-prop-2-ynyl]-pipéridme-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-4-methyl) -acrylic acid; phenyl) -prop-2-ynyl] -pipéridme-3-acetic acid

Acide (3R.4R)-4-[3-(R,S)-fluoro-3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[3-(4-chloro-3- trifluorométhyl-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3-trifluoromethyl) - acid phenyl) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-vl)propyl]-1 -[3-(2-chloro-4- trifluorométhyl-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4-trifluoromethyl-phenyl) acid) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-cbloro-5- trifluorométhvl-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-cbloro-5-trifluoromethyl-phenyl) acid) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R.4R)-4-[3-(R-S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(5-chIoro-2- inétho.\\-phen\ i yprop-2-\n\ lj-pipéridine-3-acéuque(3R, 4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chloro-2-ethoxy) phenyl] -acetate 2-piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R_S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3,5-bis-trifluoro-méthyl-phényl)-prop-2-ynyl]-pipéridine-3-acetique(3R, 4R) -4- [3- (R-S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3,5-bis-trifluoromethyl-phenyl) acid) -prop-2-ynyl] -piperidine-3-acetic

Acide (3R.4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3.5-diméthyl-phényl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-dimethyl-phenyl) -prop-2-acid) ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)piPpyl]-1 -[3-(2,4-dichloro-6-mé±yl-phényl)-prop-2-ynyl]-pipéridine-3-acétique '(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) p-pyl] -1- [3- (2,4-dichloro-6-methyl) - acid 1-phenyl) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R.S)-fluoro-3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[3-(thien-2-yl)-prop-2-ynyl]-pipéridine-3-acétique 120 2 2 99(3R, 4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) -prop-2) -acid -ynyl] -piperidine-3-acetic 120 2 2 99

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)prcpyI]-l-[3-(5-chloro-thien-2-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (5-chloro-thien-2-yl) acid) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-chIoro-thien-2-yl)-prop-2-ynyl]-pipéridine-3-acétique 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinoIin^-yl)propyl]-1 -[3-(5-méthyl-tfaien-2- yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-thien-2-yl) acid) 1-Prop-2-ynyl] -piperidine-3-acetic acid (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-1-yl) propyl] -1- [ 3- (5-methyl-tfaien-2-yl) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(3-méthyl-thien-2-yI)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (3-methylthien-2-yl) acid) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluorc>-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(thien-3-yl)-prop-2-io ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) propyl) -acrylic acid; 2-ylyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3“(l-méthyl-pynOl-2-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3 - (1-methyl-pynyl-2-yl) acid -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(l-méthyl-pyrrol-3-yl)-prop-2-ynyl]-pipéridme-3-acétique 15 Acide (3R,4R)4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thiazol-2-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methyl-pyrrol-3-yl) acid 1-Prop-2-ynyl] -piperidin-3-acetic acid (3R, 4R) 4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [ 3- (thiazol-2-yl) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)^-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(thiazol-4-yl)-prop-2-ynyl]-pipéridme-3-acétique(3R, 4R) - [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (thiazol-4-yl) -prop-2- acid ynyl] -pipéridme-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thiazol-5-yl)-prop-20 2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazol-5-yl) prop-20) -acid 2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoiO-3-(6-méÎhoxyquinolin-4-yl)propyl]-l-[3-(l-méthyl-imidazo]-2-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (1-methyl-imidazo] -2-yl acid ) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-méthyl-imidazol-4-yl)-prop-2-ynyl]-pipéridine-3-acétique 2 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méÜioxyquinolin-4-yl)propyl]-l-[3-(3-méthyl-pyra2ol- 4-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-imidazol-4-yl) acid) 1-Prop-2-ynyl] -piperidine-3-acetic acid (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methyloxyquinolin-4-yl) propyl] -1 [3- (3-methyl-pyra-2-yl) -prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyî]-l-[3-(oxazol-2-yl)-prop-2-ynyl]-pipéridine-3 -acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (oxazol-2-yl) prop-2) -acid -ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(oxazol-4-yi)-prop-30 2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-4-yl) prop-30) -acid 2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-mélhoxyquinolin-4-yl)propyl]-1 -[3-(oxazol-5-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-melhoxyquinolin-4-yl) propyl] -1- [3- (oxazol-5-yl) prop-2) -acid ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinoiin-4-yl)propyl]-1 -[3-(pyridin-2-yl)-prop-2-ynyl]-pipéridine-3 -acétique 3 5 Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(pyridm-3-yl)-prop- 2-ynyl]-pipéridine-3-acétique 12 0 2 2 100(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) prop-2) -acid -ynyl] -piperidine-3-acetic acid (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) -prop-2-ynyl] -piperidine-3-acetic acid 12 0 2 2 100

Acide (3R,4R>4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(pyridin-4-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) 4- [3- (R, S) -Fluoro-3- (6-methoxy-iminolin-4-yl) propyl] -1- [3- (pyridin-4-yl) prop-2 -acid] acid ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthox>'quinolin-4-yl)prqpyl]-1 -[3-(pyrimidin-2-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxy-quinolin-4-yl) propyl] -1 - [3- (pyrimidin-2-yl) - acid prop-2-ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-4-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-4-yl) prop-2) -acid ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-5-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (pyrimidin-5-yl) prop-2 -acid] acid ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-l-[3-(pyrazin-2-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (pyrazin-2-yl) -prop-2) -acid ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-l-[3-(pyrida2in-3-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (pyridin-3-yl) prop-2) -acid ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l -[3-(pyridazin-4-yl)-prop-2-ynyl]-pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4-yl) prop-2) -acid ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-phénylpropèn-2-yl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylpropen-2-yl] piperidine-3-acetic acid

Acide (3R4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-phénylbutèn-3-yl]pipéridine-3-acétique(3R4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4-phenylbuten-3-yl] piperidine-3-acetic acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-phénylpropyl]piperidin-3-yl}propan- 1-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3-phenylpropyl] piperidin-3-yl} propan-1-ol acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-l -[4-phénylbutyl]piperidin-3-yl}propan-1-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4-phenylbutyl] piperidin-3-yl} propan-1-oic acid

Acide (3R,4R)-3- {4-[3-{6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-fluorophényl)propyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- {6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenyl) propyl] piperidin-3-yl} propan-1 -ic acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(2-fluorophényl)butyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (2-fluorophenyl) butyl] piperidin-3-yl} propan-1-ol acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin^l-yl)propyl]-1 -[3-(3-fluorophényl)propyl]piperidin-3-yl j propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-1-yl) propyl] -1- [3- (3-fluorophenyl) propyl] piperidin-3-yl} propan-1 -ic acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(3-fluorophényl)butyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (3-fluorophenyl) butyl] piperidin-3-yl} propan-1-oic acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-£luorophényl)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) propyl] piperidin-3-yl} propan-1 acid oic

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(4-fluorophényl)butyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (4-fluorophenyl) butyl] piperidin-3-yl} propan-1 -ic acid

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,3-difluorophényl)propyl]piperidin-3-yl} propan-1 -oique 120 2 2 101(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl) propyl] piperidin-3-yl} propan-1 acid 120 2 2 101

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(2,3-difluorophényl)butyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (2,3-difluorophenyl) butyl] piperidin-3-yl} propan-1 acid -oique

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,6-difluorophényi)propyl]piperidin-3-yl}propan-l-oique 5 Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(2,6-diiluorophényl)butyl]piparidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl) propyl] piperidin-3-yl} propan-1 acid (3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (2,6-diilorophenyl) butyl] piparidin-3-yl} propan-l-oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-chlorophényl)propyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenyl) propyl] piperidin-3-yl} propan-1-ol acid

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl3-l-[4-(2-chlorophényl)butyl]io piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (2-chlorophenyl) butyl] piperidin-3-yl} propan-1-ol acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-l -[3-(3-diIorcphényl)prcpyl]piperidin-3-yl}propan-1 -oique - Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(3-chlorophényl)butyl]piperidin-3-yl}propan-l-oique 15 Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl3-l-[3-(4-chlorophàiyl)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-dihydroxyphenyl) propyl] piperidin-3-yl} propan-1-oic acid (3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (3-chlorophenyl) butyl] piperidin-3-yl} propan-1-acid (3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenyl) propyl] piperidin-3-yl} propan-1 -acidic acid oic

Acide (3R,4R)-3- {4-[3 -(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(4-cblorophényl)butyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (4-cblorophenyl) butyl] piperidin-3-yl} propan-1-oic acid

Acide (3R,4R)-3- {4-[3/6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,3-dichIorophényl)propyl]20 piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3/6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichlorophenyl) propyl] piperidin-3-yl} propan-1 acid -oique

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4 -yî)propyî]-1 -[4-(2,3-dichlorophényl)butyl]piperidin-3-yî}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (2,3-dichlorophenyl) butyl] piperidin-3-yl} propan-1 acid -oique

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,6-dichIorophényi)propyl]piperidin-3-yl}propan-1 -oique 25 Acide (3R,4R)-3-{4-[3-(6-méthoxyqumolin-4-yl)propyI]-l-[4-(2,6-dichlorophényl)butyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,6-dichlorophenyl) propyl] piperidin-3-yl} propan-1 acid (3R, 4R) -3- {4- [3- (6-Methoxyquolin-4-yl) propyl] -1- [4- (2,6-dichlorophenyl) butyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl3-l-[3-(2-méthylphényl)propyl]piperidin-3 -y 1} propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenyl) propyl] piperidin-3-yl} propan-1 -ic acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4~(2-méthylphényl)butyl] 3 o piperidin-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1 - [4 - (2-methylphenyl) butyl] -3-piperidin-3-yl} propan-1 acid -oique

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[5-(2-méthylphényl)pentyl]piperidin-3 -yl} propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinin-4-yl) propyl] -1- [5- (2-methylphenyl) pentyl] piperidin-3-yl} propan-1 -ic acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthylphényl)propyl]piperidin-3-yl}propan-l -oique 3 5 Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(3-méthylphényl)butyl]piperidin-3-yl }propan-l -oique 120 22 102(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenyl) propyl] piperidin-3-yl} propan-1 -ic acid (3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (3-methylphenyl) butyl] piperidin-3-yl} propan-1 120 22 102

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin^l-yl)propyl]-1 -[3-(4-méthylphényl)propyl]piperidin-3-yl}piopan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-1-yl) propyl] -1- [3- (4-methylphenyl) propyl] piperidin-3-yl} piopan-1-oic acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(4-méthylphényl)butyl]piperidin-3-yl} propan-1 -oique 5 Acide (3R,4R>3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-méthoxyphényl)propyl] piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (4-methylphenyl) butyl] piperidin-3-yl} propan-1-oic acid (3R, 4R) 3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenyl) propyl] piperidin-3-yl} propan-1-oic acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]- l-[4-(2-méthoxyphényl)butyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (2-methoxyphenyl) butyl] piperidin-3-yl} propan-1 -ic acid

Acide (3R,4R)-3- {4-[3-(6-inéthoxyquinolm-4-yl)propyl]-1 -[3-(3-méthoxyphényl)propyl] 10 piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Inethoxyquinol-4-yl) propyl] -1- [3- (3-methoxyphenyl) propyl] piperidin-3-yl} propan-1-acid oic

Acide (3R,4R>3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(3-méthoxyphényl)butyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (3-methoxyphenyl) butyl] piperidin-3-yl} propan-1-ol acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-méthoxyphényl)propyl]piperidin-3-yl}propan-1 -oique 15 Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(4-méthoxyphényl)butyl] piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenyl) propyl] piperidin-3-yl} propan-1-oic acid (3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (4-methoxyphenyl) butyl] piperidin-3-yl} propan-1 -acid oic

Acide (3R4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl3-1 -[3-(2-trifluorométhylphényl)propyl]piperidin-3-yl}propan-1 -oique(3R4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1 - [3- (2-trifluoromethylphenyl) propyl] piperidin-3-yl} propan-1 -ic acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(2-trifluorométhylphényl) 2 o butyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (2-trifluoromethylphenyl) -2-butyl] piperidin-3-yl} propan-1 acid -oique

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-trifluorométhylphényl)propyl]piperidin-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenyl) propyl] piperidin-3-yl} propan-1 -ic acid

Acide (3R4R)-3- {4-[3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[4-(3-trifluorométhylphényl)butyl]piperidin-3-yl }propan-1 -oique 2 5 Acide (3R,4R)-3- {4-[3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[3-(4-trifluorométhylphényl) propyl]piperidin-3-yl }propan-1 -oique(3R4R) -3- {4- [3- (6-Methyl-quinolin-4-yl) propyl] -1- [4- (3-trifluoromethyl-phenyl) butyl] -piperidin-3-yl} -propan-1 -ic acid (3R, 4R) -3- {4- [3- (6-Methyl-quinolin-4-yl) propyl] -1- [3- (4-trifluoromethyl-phenyl) -propyl] -piperidin-3-yl} propanic acid -1 -oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(4-trifluorométhylphényl)butyljpiperidin- 3 -yl} propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (4-trifluoromethylphenyl) butyl] -piperidin-3-yl} propan-1 -ic acid

Acide (3R,4R)-3- {4-[3-(6-méthoxvquinolin-4-yl)propylj-1 -[2-phénylthio-éthyl]piperidin-3- 3 o yl} propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxvquinolin-4-yl) propyl] -1- [2-phenylthio-ethyl] piperidin-3-yl} propan-1 -ic acid

Acide (3R,4R)-3- {4-[3-(6-mé±oxyquinolûM-yl)propyl]-1 -[3-phénylthio-propyl jpiperidin-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methyl-quinol-1-yl) propyl] -1- [3-phenylthio-propyl] -piperidin-1-yl} -propan-1-olic acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2-fluorophénylthio)éthyl]piperidin-3-yl}propan-1 -oique 3 5 Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-fluorophénylthio)propyl] piperidin-3 -yl} propan-1 -orque en 120 2 2 103(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (2-fluorophenylthio) ethyl] piperidin-3-yl} propan-1 -ic acid (3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenylthio) propyl] piperidin-3-yl} propan-1 -orque in 120 2 2 103

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3-fiuorophénylthio)éthyljpiperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (3-fluorophenylthio) ethyl] piperidin-3-yl} propan-1-ol acid

Acide (3R,4R)-3-{4-[3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(3-fluorophénylthio)propyl]piperidin-3-yl}propan-l-oique 5 Acide (3R,4R)-3-{4-[3-(6-métlioxyquinolm-4-yl)propyl]-l-[2-(4-fluorophényltbio)éthyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquolin-4-yl) propyl] -1- [3- (3-fluorophenylthio) propyl] piperidin-3-yl} propan-1-ol acid (3R, 4R) -3- {4- [3- (6-Methyloxyquinolm-4-yl) propyl] -1- [2- (4-fluorophenylthio) ethyl] piperidin-3-yl} propan-1-acid oic

Acide (3R,4R)-3-{4-[3-(6-niélhoxyqumolin-4-yl)propyl]-l-[3-(4-fiuorophénylthio)propyl]piperidm-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Niethyloxy-iminolin-4-yl) propyl] -1- [3- (4-fluorophenylthio) propyl] piperid-3-yl} propan-1-ol acid

Acide (3R,4R)-3-{4-[3-(6-méthoxyquiiiolin-4-yl)propyl]-l-[2-(2,3-difluorophà3ylthio)éthyl]ίο piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinyl-4-yl) propyl] -1- [2- (2,3-difluorophenylthio) ethyl] ί-piperidin-3-yl} propanic acid l-oic

Acide (3R,4R)-3-{4-[3-(6-méâ3oxyquiiiolin-4-yl)propyl]-l-[3-(2,3-difluorophényltiiio)propyl3piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxycarbonyl-4-yl) propyl] -1- [3- (2,3-difluorophenylthio) propyl] -piperidin-3-yl} propan-1 -ic acid

Acide (3R,4R)-3-{4~t3-(6-méthoxyquinolin-4-yl)piOpyl]-l-[2-(2,6-difluorophénylthio)éthyl]piperidin-3-yl}propan-l -oique 15 Acide (3R,4R)-3-{4-[3-(6-inéthoxyquinolm-4-yl)propyi]-l-[3-(2s6-difluorophényithio)propyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) p -Pyl] -1- [2- (2,6-difluorophenylthio) ethyl] piperidin-3-yl} propan-1-acid (3R, 4R) -3- {4- [3- (6-Inethoxyquinol-4-yl) propyl] -1- [3- (2-difluorophenylthio) propyl] piperidin-3-yl} propan-1 -acidic acid -oique

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl3-l-[2-(2-chlorophénylÎhio)éthyl]piperidin-3-yl}propan- 1-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (2-chlorophenylthio) ethyl] piperidin-3-yl} propan-1 -ic acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]- l-[3-(2-chlorophénylthio)propyl] 2 0 piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenylthio) propyl] piperidin-3-yl} propan-1 acid -oique

Acide (3R,4R}-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(3-chlorophàiyltbio)éÛiyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (3-chlorophenylthio) phenyl] piperidin-3-yl} propan-1 -ic acid

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-chlorophénylthio)propyî]piperidin-3-yl} propan-1 -oique 2 5 Acide (3R,4R)-3- (4-[3 -(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(4-chlorophénylthio)éthyl] piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenylthio) propyl] piperidin-3-yl} propan-1-oic acid (3R, 4R) -3- (4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (4-chlorophenylthio) ethyl] piperidin-3-yl} propan-1 -oique

Acide (3R,4R)-3- {4~[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-chlorophénylthio)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4 - [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenylthio) propyl] piperidin-3-yl} propan-1 -ic acid

Acide (3R,4R)-3-{4-[3-(6-méihoxyquinolin-4-yl)propyi]-l-[2-(2,3-dichlorophênylîhio)éthyl330 piperidin-3-yl}propan-1-oique(3R, 4R) -3- {4- [3- (6-Methyloxyquinolin-4-yl) propyl] -1- [2- (2,3-dichlorophenylthio) ethyl] piperidin-3-yl} propan-1-acid oic

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,3-dichlorophénylthio)propyl3piperidin-3-yl}propan- 1-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichlorophenylthio) propyl] piperidin-3-yl} propan-1 -ic acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2,6-dichlorophénylthio)éthyl]piperidin-3-yl}propan-1 -oique 3 5 Acide (3R,4R)-3- {4~[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,6-dichlorophénylthio)propyl] piperidin-3-yl}propan-1 -oique 120 2 2 104(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (2,6-dichlorophenylthio) ethyl] piperidin-3-yl} propan-1 acid (3R, 4R) -3- {4 - [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-dichlorophenylthio) propyl] piperidin-3-yl } propan-1 -oic 120 2 2 104

Acide (3R,4R>3-{4-[3-<6-méthoxyquinoIin-4-yl)propyl]-l-[2-(2-méthylphénylthio)éthyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinin-4-yl) propyl] -1- [2- (2-methylphenylthio) ethyl] piperidin-3-yl} propan-1-ol acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2-niéthylphénylthio)propyl]piperidin-3-yl}propan-1 -oique 5 Acide (3R,4R)-3- {4-[3-(6-méâioxyquinolin-4-yl)propyl]-1 -[2-(3-méthylphénylthio)éthyl] piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenylthio) propyl] piperidin-3-yl} propan-1 -ic acid (3R, 4R) -3- {4- [3- (6-Methioxyquinolin-4-yl) propyl] -1- [2- (3-methylphenylthio) ethyl] piperidin-3-yl} propan-1-acid oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-<3-méthylphénylthio)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenylthio) propyl] piperidin-3-yl} propan-1 -ic acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(4-méthylphénylthio)éthyl] 10 piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (4-methylphenylthio) ethyl] piperidin-3-yl} propan-1-acid oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-méthylphénylthio)propyl]piperidm-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenylthio) propyl] piperid-3-yl} propan-1-ol acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2-trifluorométhylhénylthio)éthyl]piperidin-3-yl}propan-1 -oique 15 Acide (3R,4R)-3 - {4- [3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-triflurométhylphényithiio) propyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (2-trifluoromethyl-phenylthio) -ethyl] -piperidin-3-yl} propan-1 -ic acid (3R, 4R) -3 - {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluromethylphenyl) thio] propyl] piperidin-3-yl} propan-1-acid oic

Acide (3R,4R)-3- [4-[3-(6-rnéthoxyquinolinA-yl)propyl]-l -[2-(3-trifluorométhylhâiylthio)éthyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- [4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethyl-ethylthio) ethyl] piperidin-3-yl} propan-1 -ic acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-triflurométhylphénylthio) 2 o propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluromethylphenylthio) -2-propyl] piperidin-3-yl} propan-1 acid -oique

Acide (3R,4R)-3- {4-[3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[2-(4-îrifluorométhylhénylthio)éthyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methyl-quinolin-4-yl) propyl] -1- [2- (4-trifluoromethyl-enylthio) -ethyl] -piperidin-3-yl} -propan-1 -acid -oique

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-triflurométhylphénylthio)propyl]piperidin-3-yl}propan-1 -oique 2 5 Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2-méthoxyphénylthio)éthyl] piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluromethylphenylthio) propyl] piperidin-3-yl} propan-1 -ic acid (3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (2-methoxyphenylthio) ethyl] piperidin-3-yl} propan-1 -oique

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinoEn-4-yl)propyl]-1 -[3-(2-méthox\phénylthio)propyl]piperidin-3-yI} propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinin-4-yl) propyl] -1- [3- (2-methoxenophenylthio) propyl] piperidin-3-yl} propan-1 acid -oique

Acide (3R.4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3-méthoxyphénylthio)éthyl]30 piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (3-methoxyphenylthio) ethyl] piperidin-3-yl} propan-1-acid oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[3-(3-méthoxyphénylthio)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinin-4-yl) propyl] -1- [3- (3-methoxyphenylthio) propyl] piperidin-3-yl} propan-1 -ic acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(4-méthoxyphénylthio)éthyl]piperidin-3-yl}prôpan-l-oique 3 5 Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-méthoxyphénylthio)propyl] piperidin-3-yl }propan-1 -oique 120 2 2 105(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (4-methoxyphenylthio) ethyl] piperidin-3-yl} propan-1-ol acid (3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenylthio) propyl] piperidin-3-yl} propan-1 120 2 2 105

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[cyclcpropylméthyl]piperidin-3-yl}prqpan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [cyclopropylmethyl] piperidin-3-yl} propan-1-ol acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-l -[2-(cycloprqpyl)éthyl]piperidin-3-yl}prqpan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (cyclopropyl) ethyl] piperidin-3-yl} propan-1-ol acid

Acide (3R,4R)-3- {4-[3-(6-méflioxyquinolin-4-yl)propyl]-1 -[cyclobutylméthyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methylquinolin-4-yl) propyl] -1 - [cyclobutylmethyl] piperidin-3-yl} propan-1-ol acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyî]-1 -[2-(cyclobutyl)éthyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (cyclobutyl) ethyl] piperidin-3-yl} propan-1-ol acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[cyclopentylméthyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [cyclopentylmethyl] piperidin-3-yl} propan-1-ol acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(cyclopentyl)éthyl]piperidin-3-yl}propan-1-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentyl) ethyl] piperidin-3-yl} propan-1-oic acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[cyclohexylméthyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [cyclohexylmethyl] piperidin-3-yl} propan-1-ol acid

Acide (3R,4R)-3- {4-[3-(6-métboxyquinolin-4-yl)propyl]-1 -[2-(cyclohexyl)éthyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidin-3-yl} propan-1-ol acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-l -[2-(cyclopropylthio)éthyl]piperidin-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (cyclopropylthio) ethyl] piperidin-3-yl} propan-1 -ic acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(cyclopropylthio)propyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (cyclopropylthio) propyl] piperidin-3-yl} propan-1-ol acid

Acide (3R-4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(cyclobutylthio)éiliyl]piperidin-3 -y i} propan-1 -oique(3R-4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (cyclobutylthio) ileyl] piperidin-3-yl} propan-1-oic acid

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(cyclobuiyithiopropyl]piperidin-3-yi} propen-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (cyclobuiyithiopropyl) piperidin-3-yl} propen-1-oic acid

Acide (3R)4R)-3-{4-[3-(6-métbo;;yquiuolin-4-yl)propyl3-l-[2-(cydopsntyltbio)éthyl]piperidin-3-yl}propan- 1-oique(3R) 4R) -3- {4- [3- (6-Methyl-4-yl) -propyl) -1- [2- (cydopantylthio) ethyl] piperidin-3-yl} propan-1-ol acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(cyclopentylthio)propyl]piperidin-3 -yl} propan- 1-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (cyclopentylthio) propyl] piperidin-3-yl} propan-1 -ic acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(cyclohexylthio)éthyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperidin-3-yl} propan-1 -ic acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-(cyclohexylthio)propyl]piperidin-3 -yl} propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquolin-4-yl) propyl] -1- [3- (cyclohexylthio) propyl] piperidin-3-yl} propan-1 -ic acid

Acide (3R,4R)-3- {4-[3-(6-métboxyquinolin-4-yl)propyl]-1 -[2-méthylîhioéthyl]piperidin-3-yl} propan-1-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2-methylthioethyl] piperidin-3-yl} propan-1-oic acid

Acide (3R,4R)-3- {4-[3-(6-méîboxyquinolin-4-yl)propyl]-1 -[3-méthylthiopropyl]piperidin-3-yl}propan-l-oique 1 2 0 2 2 106(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3-methylthiopropyl] piperidin-3-yl} propan-1-ol acid 1 2 0 2 2 106

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyI]-1 -[2-éthylthioéthyl]piperidin-3-yl}prqpan-loique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2-ethylthioethyl] piperidin-3-yl} propanol

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-éthylthiopropyl]piperidin-3-yl} propan-1-oique 5 Acide (3R,4R)-3- {4-[3<6-méthoxyquinolm-4-yl)propyl]-1 -[2-(n-propyIthio)éthyl]piperidin-3- yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3-ethylthiopropyl] piperidin-3-yl} propan-1-oic acid (3R, 4R) -3- {4- [3-methoxyquinol-4-yl) propyl] -1- [2- (n-propylthio) ethyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(6-méîhoxyquinolin-4-yl)propyl]-l-[3-(n-propylthio)propyl]piperidin-3 -yl }propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (n-propylthio) propyl] piperidin-3-yl} propan-1 -ic acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(n-butylthio)éthyl]piperidin-3-10 yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (n-butylthio) ethyl] piperidin-3-yl} propan-1-acid oic

Acide (3R,4R)-3- {4-[3-(6-méüioxyqumolin-4-yl)propyl]-1 -[3-(n-butylthio)propyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (n-butylthio) propyl] piperidin-3-yl} propan-1-ol acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(thien-2-yl)propyl]piperidin-3-yl }propan-1-oique 15 Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(thien-2-yl)butyl]piperidin-3- yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) propyl] piperidin-3-yl} propan-1 acid (3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (thien-2-yl) butyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[2-(thien-2-yl)tbioéîhyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinin-4-yl) propyl] -1- [2- (thien-2-yl) benzothelyl] piperidin-3-yl} propan-1 acid -oique

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(thien-2-yl)thiopropyl] 2 o piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) thiopropyl] -2-piperidin-3-yl} propanic acid -1 -oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(5-chloro-thien-2-yl)propyl]piperidin-3-yl}propan- 1-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (5-chloro-thien-2-yl) propyl] piperidin-3-yl acid } prop-1-oique

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(5-chloro-ihien-2-yl)butyl]piperidin-3-yl }propan-1 -oique 2 5 Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(5-cbloro-thien-2-yl)thioéthyl] piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (5-chloro-iHien-2-yl) butyl] piperidin-3-yl acid } Propan-1-Oic Acid (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (5-cbloro-thien-2-yl} ) thioethyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(6-mé±oxyquinolin^-yl)propyl j-1 -[3-(5-chloro-thien-2-yl)thiopropyl]piperidin-3-yl) propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methyl-oxyquinolin-1-yl) propyl] -1- [3- (5-chloro-thien-2-yl) thiopropyl] piperidin-3- acid yl) propan-1-oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinoIin-4-yl)propy]]-1 -[3-(3-chIoro-thien-2-yl)propyl] 3 o piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinino-4-yl) propyl] -1- [3- (3-chloro-thien-2-yl) propyl] -3-piperidinic acid; 3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(3-chloro-thien-2-yl)butyl]piperidin-3-yl} propan-1 oique , Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3-chloro-lhien-2-yî)thioéthyl] , piperidin-3-yl}propan-l oique 3 5 Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-chloro-thien-2-yl)thiopropyl] x piperidin-3-yl}propan-l oique 120 2 2 107(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (3-chloro-thien-2-yl) butyl] piperidin-3-yl acid } Propan-1ic acid, (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chloro-1-yl) -2-yl) thioethyl acid. ], (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro) -3-yl} -propan-1-ol -thien-2-yl) thiopropyl] x-piperidin-3-yl} propan-1-ol 120 2 2 107

Acide (3R,4R)-3-{4-[3-(b-méthoxyquinolin-4-yl)propyl]-l-[3-(5-méthyl -thien-2-yl)propyl]piperidin-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (B-Methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthien-2-yl) propyl] piperidin-3-yl acid } propan-l-oique

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(5-méthyl -thien-2-yl)butyl]piperidin-3-yl}propan-l-oique 5 Acide (3R,4R)-3-{4-[3-(6-méÜioxyquinolin^4-yl)propyl]-l-[2-(5-nîéthyl -thien-2-yl)thioéthyl]piperidin-3-yl}propan- 1-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (5-methylthien-2-yl) butyl] piperidin-3-yl acid Propan-1-oic acid (3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (5-ethyl-thien-2-yl)} thioethyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(5-niéthyl -thien-2-yl)thio-propyl]piperidin-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthien-2-yl) thio-propyl] piperidin-3-acid -yl} propan-l-oic

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-méthyl-thien-2-yl)propyl] 10 piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-methylthien-2-yl) propyl] piperidin-3- acid yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(6-mélhoxyquinolin-4-yl)propyl]-l -[4-(3-méthyl -tbien-2-yl)butyl]piperidm-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (3-methyl-2-yl) butyl] piperid-3-yl acid } propan-1 -oic

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(3-méthyl-thien-2-yl)thioéthyl]piperidin-3-yl}propan- 1-oique 15 Acide (3R4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyî]-l-[3-(3-métliyl -thien-2-yl)thio-propyl]piperidin-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (3-methylthien-2-yl) thioethyl] piperidin-3-yl acid Propan-1ic acid (3R4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylthien-2-yl) thio] propyl] piperidin-3-yl} propan-1-ol

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(thien-3-yl)propyl]piperidm-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) propyl] piperid-3-yl} propan-1 acid -oique

Acide (3R,4R)-3 - {4-[3-(6-méthoxyquinolirsA-yl)propyl]-1 -[4-(thien-3-yl)butyl]piperidin-3-20 yl}propan-l-oique(3R, 4R) -3 - {4- [3- (6-Methoxyquinol-1-yl) propyl] -1- [4- (thien-3-yl) butyl] piperidin-3-20-yl} propan-1-acid oic

Acide (3R,4R)-3-{4-[3-(6-ruéftox)?q«inolm-4-yl)propyl]-1 -[2-(ibien-3-yl)thioétliyl]piperidin-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (6-Rufeftox) -5-enolm-4-yl) propyl] -1- [2- (ibien-3-yl) thioethyl) piperidin-3- acid yl} propan-l-oic

Acide (3R,4 R.)-3 - {4-f3-(6-inéthoxyquinolin-d-yl)prcpyl]-1 -[3-(thien-3-yl)îhiopropyl]piperidin-3-yI} propan- 1 -oique 25 Acide (3R/iR.)-3-{4-[3-(6-méihoxyquinolin-4-yî)propyl]-l-[3-(fiir-2-yl)propyl]piperidin-3-yl}propan-l-oique(3R, 4 R) -3- {4-[3- (6-Methoxyquinolin-d-yl) propyl] -1- [3- (thien-3-yl) hydro] propyl] piperidin-3-yl} propanic acid; 1- (3RlR) -3- {4- [3- (6-Methyloxyquinolin-4-yl) propyl] -1- [3- (1-yl) propyl] piperidin-3- acid yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(fur-2-yl)butyl]piperidin-3-yl}propan-1-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (fur-2-yl) butyl] piperidin-3-yl} propan-1 acid -oique

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(iur-2-yl)thioéùiyl]piperidin-3-3 0 yljpropan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (iur-2-yl) thio] ilyl] piperidin-3-yl} propan-1 acid -oique

Acide (3R,4R)-3- {4-[3-(6-méîhoxyquinolin-4-yl)propyl]-1 -[3-(fur-2-yl)thiopropyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (fur-2-yl) thiopropyl] piperidin-3-yl} propan-1 acid -oique

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(fur-3-yl)propyl]piperidin-3-yl} propan-1-oique 3 5 Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4~yl)propyl]-1 -[4-(fur-3-yl)butyl]piperidin-3-yl}propan-1-oique 1 20 2 2 108(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (fur-3-yl) propyl] piperidin-3-yl} propan-1 acid (3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (fur-3-yl) butyl] piperidin-3-yl } propan-1-oic 1 20 2 2 108

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(fur-3-yl)thioéthyl]piperidin-3-yi}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (fur-3-yl) thioethyl] piperidin-3-yl} propan-1 acid -oique

Acide (3R4R>3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(fur-3-yl)thiopropyl3piperidin-3-yl}propan- 1-oique(3R4R) 3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (fur-3-yl) thiopropyl) -piperidin-3-yl} propan-1-ol acid

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-l -[3-( 1 -mé1hyl-pynOl-2-yl)propyl]piperidin-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (1-methylphyn-1-yl) propyl] piperidin-3-yl acid } propan-l-oique

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-( 1 -méthyl-pyirol-2-yl)butyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (1-methyl-pyirol-2-yl) butyl] piperidin-3-yl acid } propan-1 -oic

Acide (3R4R)-3- {4-[3-(6-méthoxyquinolm-4-yl)propyl]-1 -[2-< 1 -méthyl-pyrrol-2-yl)thio-éthyl]piperidin-3-yl}propan-1-oique(3R4R) -3- {4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [2- (1-methyl-pyrrol-2-yl) thio-ethyl] piperidin-3-yl acid } propan-1-oic acid

Acide (3R4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(l-méthyl-pyiTol-2-yl)thio-propyl]piperidin-3-yl}propan-l-oique(3R4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (1-methyl-pylol-2-yl) thio-propyl] piperidin-3-yl acid } propane-l-oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-( 1 -méthyl-pyrrol-2-yl)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (1-methyl-pyrrol-2-yl) propyl] piperidin-3-yl acid } propan-1 -oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-( 1 -méthyl-pyirol-3-yl)butyl]piperidin-3-yî}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (1-methyl-pyirol-3-yl) butyl] piperidin-3-yl acid } propan-1 -oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)pxüpyl]-1 -[2-( 1 -méthyl-pyirol-3-yl)thio-éthyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) pexyl] -1- [2- (1-methyl-pyridol-3-yl) thio-ethyl] piperidin-3-acid -yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-( 1 -méthyl-pyirol-3-yl)thio-propyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (1-methyl-pyridol-3-yl) thio-propyl] piperidin-3-acid -yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(thiazol-2-yl)propyl]piperidin-3-yl}propan- 1-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (thiazol-2-yl) propyl] piperidin-3-yl} propanic acid -oique

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(thiazol-2-yl)butyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (thiazol-2-yl) butyl] piperidin-3-yl} propan-1 acid -oique

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(thiazol-2-yl)thioéthyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (thiazol-2-yl) thioethyl] piperidin-3-yl} propan-1 acid -oique

Acide (3R.4R)-3- {4-[3-(6-méthoxyquinoün-4-yl)propyl]-1 -[3-(thiazol-2-yl)thiopropyl]piperidin-3-yl J propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquino-4-yl) propyl] -1- [3- (thiazol-2-yl) thiopropyl] piperidin-3-yl} propan-1 acid -oique

Acide (3R,4R)-3- {4-[3-(6-mé±oxyquinolin-4-yl)propylj- l-[3-(l -méthyl-imidazol-2-yl)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methyl-quinolin-4-yl) propyl] -1- [3- (1-methyl-imidazol-2-yl) propyl] piperidin-3- acid yl} propan-1 -oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-( 1 -méthyl-imidazol-2-yl)butyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (1-methylimidazol-2-yl) butyl] piperidin-3-yl acid } propan-1 -oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-( 1 -méthyl-imidazol-2-yl)thio-éthyl]piperidin-3-yl}propan-1 -oiqtie(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (1-methylimidazol-2-yl) thio-ethyl] piperidin-3-acid -yl} propan-1-iqtie

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin^-yl)propyl]-1 -[3-( 1 -méthyl-imidazol-2-yl)thio-propyl]piperidin-3-yl}propan-1 -oique 120 2 2 109(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-1-yl) propyl] -1- [3- (1-methylimidazol-2-yl) thio-propyl] piperidin-3- acid yl} propan-1 -oic 120 2 2 109

Acide (3R,4R)-3- {4-[3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-(3-méthyl-inùdazol-4-yl)propyl]piperidin-3-yl}propaQ-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquolin-4-yl) propyl] -1- [3- (3-methyl-imidazol-4-yl) propyl] piperidin-3-yl acid } Propaq-l-oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyqumolin-4-yl)propyl]-1 -[4-(3-niédiyl-nnidazol-4-yl)butyl]piperidm-3-yl}propan-l-oique 5 Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(3-méthyl-iinidazol-4-yl)thioéthyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquolin-4-yl) propyl] -1- [4- (3-norbornyl-nnidazol-4-yl) butyl] piperid-3-yl acid Propan-1-oic acid (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methyl-1inidazol-4-yl)} thioethyl] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yI)propyl]-l-[3-(3-méthyl-imidazol-4-yl)thiopropyl]piperidin-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-imidazol-4-yl) thiopropyl] piperidin-3-yl acid } propan-l-oique

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-xnéthyl-pyra2ol-4-yl) 10 propyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-pyraol-4-yl) propyl] piperidin-3- acid yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(3-méthyl-pyrazol^-yl)butyl]piperidin-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (3-methyl-pyrazol-yl) butyl] piperidin-3-yl} acid propan-l-oic

Acide (3R,4R)-3-{4-[3-(6-mélhoxyquinolin-4-yl)propyl]-l-[2-(3-méùiyl-pyrazol-4-yl)thioéihyl]piperi<Ün-3-yl}propan-l-oique 15 Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-méthyl-pyra2ol-4-yl)thiopropyl]piperidin-3-yl}propan- 1-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (3-methyl-pyrazol-4-yl) thioheyl] piperyl} -3-ene (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-pyrazol-4-yl} propan-1-yl) yl) thiopropyl] piperidin-3-yl} propan-1-ol

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]- l-[3-(oxazol-2-yl)propyl]piperidm-3-yl}propan-1-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) propyl] piperid-3-yl} propan-1 acid -oique

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(oxazol-2-yl)butyl]piperidin-3-20 yl }propan-1-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (oxazol-2-yl) butyl] piperidin-3-20-yl} propanic acid 1-oic acid

Acide(3RylR)-3-{4 -[3-(6-méîhoxjrq,mioIin-d-yi)propyl]-l-[2-(ox.a2ol-2-y3)tbioétbyl]piperidiu-3-yl}propan-1 - oique(3RylR) -3- {4 - [3- (6-methyloxy) -methyl-d-yl) propyl] -1- [2- (oxazol-2-yl) benzothelyl] piperidin-3-yl} propanic acid -1 - oique

Acide (3R,4R)-3-{4-f3-(6-méüioxyquinolûi-4-yl)iiropyî]-l“[3“(oxa2oî-2-yl)Îbiopjropyl] pipcridin-3-yl}propan-1 - oi que 25 Acide (.'R/iR)-3-{4-[3<ô-mcÎbo,;ycpiiüolin-4-yi)i)iopyl]-l-[3-(i^'xidiii-2-y3)propyl]piperidin- 3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methioxyquinolin-4-yl) -1-yl] -1-yl} [3 - (oxa-2-yl) bipyropyl] pipcridin-3-yl} propan-1 - that (R, R) -3- {4- [3-hydroxy-4-yl) -opoly] -1- [3- (1-yl) -2-yl) -3-ylbicyclo-2-yl] ) propyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(pyridin-2-yl)butyl]piperidin-3-yl} propan- 1-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-2-yl) butyl] piperidin-3-yl} propanic acid -oique

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyridin-2-yl)thioéthyl] 30 piperidm-3-yl}propan- 1-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-yl) thioethyl] piperid-3-yl} propanic acid 1-oic acid

Acide (3R,4R)-3- {4-[3-(6-métboxyquinolm-4-yl)propyl]-1 -[3-(pyridin-2-yl)thiopropyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Metboxyquinol-4-yl) propyl] -1- [3- (pyridin-2-yl) thiopropyl] piperidin-3-yl} propan-1 acid -oique

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridin-3-yl)propyl]piperidin-3-yl}propan-1 -oique 3 5 Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolm-4-yl)propyl]-l-[4-(pyridm-3-yl)butyl]piperidin-3- yl}propan-l-oique 120 2 2 110(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl) propyl] piperidin-3-yl} propan-1 acid (3R, 4R) -3- {4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [4- (pyrid-3-yl) butyl] piperidin-3-yl } propan-l-oic 120 2 2 110

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-{pyridin-3-yl)thioéthyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-3-yl) thioethyl] piperidin-3-yl} propan-1 acid -oique

Acide (3R,4R>3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridin-3-yl)thiopropyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl) thiopropyl] piperidin-3-yl} propan-1-acid oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[3-(pyridin-4-yl)propyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinino-4-yl) propyl] -1- [3- (pyridin-4-yl) propyl] piperidin-3-yl} propan-1 acid -oique

Acide (3R,4R}-3-{4-[3-(6-méthoxyquinolm-4-yl)propyl]-l-[4-(pyridm-4-yl)butyl]piperidin-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [4- (pyrid-4-yl) butyl] piperidin-3-yl} propan-1 acid -oique

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[5-(pyridin-4-yl)pentyl]piperidm-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [5- (pyridin-4-yl) pentyl] piperid-3-yl} propan-1 acid -oique

Acide (3R,4R }-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyridin-4-yl)thioéthyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-4-yl) thioethyl] piperidin-3-yl} propan-1 acid -oique

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-l -[3-(pyridin-4-yl)thiopropyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl) thiopropyl] piperidin-3-yl} propan-1 acid -oique

Acide (3R4R >-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-2-yl)propyljpiperidin-3 -yl ; propan-1 -oique(3R4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) propyl] -piperidin-3-yl} propan-1-oic acid

Acide (3R,4Rr3- {4-[3-(6-méthoxyquinoIin-4-yl)propyl]-l-[4-(pyriinidin-2-yl)butyi]piperidin-3-yl} propan-1 -oique(3R, 4Rr3- {4- [3- (6-Methoxyquinin-4-yl) propyl] -1- [4- (pyriinidin-2-yl) butyl] piperidin-3-yl} propan-1-oic acid

Acide (3R,4R }-3- {4-[3-<6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyrimidin-2-yl)thioéthyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidin-2-yl) thioethyl] piperidin-3-yl} propan-1 acid -oique

Acide (3R.4R >-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-2-yl)thiopropyl]piperidin-3-yl ; propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) thiopropyl] piperidin-3-yl} propan-1 acid -oique

Acide (3R,4R >-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyriniidin-4-yl)propyl]piperidin-3-yl \ propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl) propyl] piperidin-3-yl] propan-1 acid -oique

Acide (3R,4R>-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(pyrimidin-4-yl)butyl]piperidin-3-yl propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidin-4-yl) butyl] piperidin-3-yl propan-1 acid oic

Acide (3R.4R /-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(pyrimidin-4-yl)thioéthyI]piperidin-3-y]. propan-1 -oique(3R, 4 R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidin-4-yl) thioethyl] piperidin-3-yl] propanic acid; 1 -Oic

Acide (3R.4R y-3- {4-[3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(pyriraidin^-yl)thiopropyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [3- (pyrimidin-4-yl) thiopropyl] piperidin-3-yl} propan-1 -acidic acid oic

Acide (3R,4R >-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-5-yl)propyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-5-yl) propyl] piperidin-3-yl} propan-1 acid -oique

Acide (3R4R /-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(pyrimidin-5-yl)butyl] % piperidin-3-yl ; propan-1 -oique(3R4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidin-5-yl) butyl]% piperidin-3-yl} propan-1-acid oic

Acide (3R,4R >-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyrimidin;5-yl)thioéthyl]piperidin-3-yl ; propan-1 -oique 1 20 2 2 111(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (pyrimidin; 5-yl) thioethyl] piperidin-3-yl} propan-1 acid -oic 1 20 2 2 111

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-5-yl)thiq)ropyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-5-yl) thio] propyl] piperidin-3-yl} propanic acid -l-oic

Acide (3R,4R)-3- {4-[3-(6-niéthoxyquinolin-4-yl)propyl]-1 -[3-(pyrazin-2-yl)propyi]piperidin-3-yl}propan-l-oique 5 Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(pyrazin-2-yl)butyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) propyl] piperidin-3-yl} propan-1 acid (3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (pyrazin-2-yl) butyl] piperidin-3-yl} propan-l-oic

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolm-4-yl)propyl]-l-[2-(pyrazin -2-yl)tbioéthyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [2- (pyrazin-2-yl) t-butyl] piperidin-3-yl} propan-1 acid -oique

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(pyra2in-2-yl)thiopropyl] 10 piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyrain-2-yl) thiopropyl] piperidin-3-yl} propanic acid l-oic

Acide (3R,4R)-3-{4-[3-(6-niéÜioxyquinolin-4-yl)propyl]-l-[3-(pyridazin-3-yi)propyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methylquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) propyl] piperidin-3-yl} propan-1 acid -oique

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(pyridazin-3-yl)butyl]piperidin-3-yl}propan-l -oique 15 Acide (3R,4R)-3- {4-[3-(6-méthoxyqumolin-4-yl)propyl]-1 -[2-(pyridazin-3-yl)ihioéthyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (pyridazin-3-yl) butyl] piperidin-3-yl} propan-1 acid (3R, 4R) -3- {4- [3- (6-Methoxyquolin-4-yl) propyl] -1- [2- (pyridazin-3-yl) i-hydroxyethyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(6-méihoxyquinolin-4-yl)propyl3-l-[3-(pyridazin-3-yl)thiopropyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methyloxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) thiopropyl] piperidin-3-yl} propan-1 acid oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[3-(pyridazin-4-yl)propyl] 20 piperidin-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinin-4-yl) propyl] -1- [3- (pyridazin-4-yl) propyl] piperidin-3-yl} propanic acid l-oique

Acide (3R/3R)-3-{4-[3-(6-méünxyquinolm-4-yi)prûpyl]-l-[4-Q)yîiâaztn-4-yl)buÎyi]piperidin-3-yl}proîîQn-l· oique(3R / 3R) -3- {4- [3- (6-Methyl-quinolin-4-yl) propyl] -1- (4-yl) -azal-4-yl) -benzyl) piperidin-3-yl} -acrylic acid; oic

Acide (3R/,R)-3- {4-[3 (6-rn éthoxyqu’nolin- 4 -y!)propyl]-1 -[2-{j')yikiazin-4-yl)tbioéîiiyl]pipeiidifi-3-y!}pi oomi- 1 -c«que 2 5 Acide (3R,4R)-3 · {4-[3- (6-méihoxyqüûiolin-4-yî)propylj-1 -[3-(pyridazin-4-yi)thiopropyl] piperidin-3-yl}propan-l -oique(3 R, R) -3- {4- [3- (6-ethoxyquinolin-4-yl) propyl] -1- [2- (yl) yikazin-4-yl) tbio (piperyl) piperidic acid; 3 (2R, 4R) -3- {4- [3- (6-Methyloxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4) -acetate -yi) thiopropyl] piperidin-3-yl} propan-l-oic

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-phényl-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3-phenyl-prop-2-ynyl] -piperidin-3-yl} propan-1 acid -oique

Acide (3R,4R)-3-{4-[3-(6-mé&amp;oxyquinolin-4-yl)propyl]-l-[3-(2-fluoro-phényl)-prop-2-ynyl] 3 o piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxy-4-yl) propyl] -1- [3- (2-fluoro-phenyl) -prop-2-ynyl] -ocoic acid piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-fluoro-phényl)-prop-2-ynyI]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-phenyl) -prop-2-yl] -1-piperidin-3- acid yl} propan-1 -oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-fluoro-phényl)-prop-2-ynyl]piperidin-3-yl}propan-l -oique 3 5 Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-cbloro-phényl)-prop-2- ynyl]-piperidin-3 -yl} propan-1 -oique Ï12 Ο 2 2 112(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-fluoro-phenyl) -prop-2-ynyl] piperidin-3- acid (3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-c-chlorophenyl) -propyl) propan-1-ol 2-ynyl] -piperidin-3-yl} propan-1 -oic 12 12 2 112

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-chloro-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-phenyl) -prop-2-ynyl] -piperidin-3-acid yl} propan-l-oic

Acide (3R,4R)-3- {4-[3-(6-méîhoxyquinolin-4-yl)propyl]-1 -[3-(4-chloro-phényl)-prop-2-ynyl]-piperidm-3-yl}propan-l-oique 5 Acide (3R,4R)-3- {4-[3-(6-méthoxyqumolm-4-yl)propyl]-1 -[3-(2-méthyl-phényl)-prop-2- ynyl]-piperidin-3-yl } propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-phenyl) -prop-2-ynyl] -piperid-3-acid (3R, 4R) -3- {4- [3- (6-Methoxyqumol-4-yl) propyl] -1- [3- (2-methyl-phenyl) propyl) -propan-1-yl -2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl-phényl)-prop-2-ynyl]-piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-phenyl) -prop-2-ynyl] -piperidin-3-acid -yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-méthyl-phényl)-prop-2-io ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-methyl-phenyl) -prop-2-yl] -ylpiperidinic acid; 3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(2-trifiuoroméûiyl-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [3- (2-trifluoromethyl-phenyl) -prop-2-ynyl] -piperidin-3-acid -yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolm-4-yl)propyl]-l-[3-(3-trifluoromé±yl-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique 15 Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-trifluorométhyl-phényl)- prop-2-ynyl]-piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [3- (3-trifluoromethyl-1-phenyl) -prop-2-ynyl] -piperidine -3-yl} propan-1-oic acid (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenyl)) - prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-méthoxy-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxy-phenyl) -prop-2-ynyl] -piperidin-3-acid -yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthoxy-phényl)-prop-2-2 o ynvl]-piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxy-phenyl) -prop-2-yl] -piperidine -3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[3-(4-méthoxy-phényl)-prop-2-vnyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methyl-quinolin-4-yl) propyl] -1- [3- (4-methoxy-phenyl) -prop-2-ynyl] -piperidine -3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3,4-difluoro-phényl)-prop-2-ynyl]-piperidin-3-yl } propan-1 -oique 2 5 Acide (3R,4R)-3- {4-[3-(6-mé±oxyquinolinA-yl)propyl]-1 -[3-(2,4-difluoro-phényl)-prop-2- ynyl]-piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3,4-difluoro-phenyl) -prop-2-ynyl] -piperidine -3-yl} propan-1-oic acid (3R, 4R) -3- {4- [3- (6-methoxyquinolin-A-yl) propyl] -1- [3- (2,4-difluoro)} phenyl) prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R4R)-3- {4-[3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-(3,4-dichloro-phényl)-prop-2->Tiy]]-piperidin-3-y] ) propan-1 -oique(3R4R) -3- {4- [3- (6-Methoxyquolin-4-yl) propyl] -1- [3- (3,4-dichloro-phenyl) -prop-2-> Ti]] -piperidine -3-y]) propan-1-oic

Acide (3R-4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,3-dichloro-phényl)-prop-2- 3 0 ynyl]-piperidin-3-yl}propan-l-oique(3R-4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichloro-phenyl) -prop-2-ynyl] acid -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,4-dichloro-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,4-dichloro-phenyl) -prop-2-ynyl] -piperidine -3-yl} propan-1-oic

Acide (3R,4R>3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,4,6-trichloro-phényl)-prop-2-ynyl]-piperidin-3-yl }propan-1 -oique 3 5 Acide (3R,4R)-3- {4-[3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[3-(3,5-dichloro-phényl)-prop-2- ynyl]-piperidin-3-yl }propan-1 -oique 120 2 2 113(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trichlorophenyl) prop-2-ynyl] - acid Piperidin-3-yl} propan-1-oic acid (3R, 4R) -3- {4- [3- (6-methoxyquinin-4-yl) propyl] -1- [3- dichloro-phenyl) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic 120 2 2 113

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin4-yl)propyl]-l-[3-(4-chloro-3-fluoro-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3-fluoro-phenyl) -prop-2-ynyl] -piperidine -3-yl} propan-l-oic

Acide (3R,4R)-3- {4-[3-(6-métboxyquinolm-4-yl)propyl]-l -[3-(3-chloio-4-fluoro-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique 5 Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-chloro-4-fluoro-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-4-fluoro-phenyl) -prop-2-ynyl] acid -piperidin-3-yl} propan-1-oic acid (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenyl) -2- 4-fluoro-phenyl) -prop-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-l -[3-(3-chloro-5-fluoro-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique-(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-5-fluoro-phenyl) -prop-2-ynyl] acid -piperidin-3-yl} propan-l-oique-

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinoIin-4-yl)propyl]-l -[3-(4-chloro-2-fluoro-phényl)-10 prop-2-ynyl]-piperidm-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinyl-4-yl) propyl] -1- [3- (4-chloro-2-fluoro-phenyl) -10-prop-2-ynyl) -acid ] -piperidm-3-yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(6-méîhoxyquinolin-4-yl)propyI]-l-[3-(3-fluoro-4-méthyi-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-4-methyl-phenyl) -prop-2-ynyl] acid -piperidin-3-yl} propan-l-oic

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(4-chIoro-3-triiluorométhyl-pbényl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique 15 Acide (3R,4R)-3-{4-[3-(6-niéthoxyquinoiin-4-yl)propyl]-l-[3-(2-chloro4-trifluorométhyi-phényl)-prop-2-ynyl3-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3-triiloromethyl-pbenyl) -prop-2-ynyl] acid -piperidin-3-yl} propan-1-oic acid (3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro)} trifluoromethyl-phenyl) -prop-2-ynyl-3-piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-<6-méûioxyquinolin-4-yl)propyl]-1 -[3-(2-chloro-5-trifluorométbyl-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methioxyquinolin-4-yl) propyl] -1- [3- (2-chloro-5-trifluoromethyl-phenyl) -prop-2-ynyl] acid -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]- l-[3-(5-chloro-2-méthoxy-phényl)-2 0 prop-2-ynyl]-piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (5-chloro-2-methoxy-phenyl) -2-prop-2- acid ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinoîin-/l-yl)propyl]-l-[3-(3,5-bis-trifluorométhyl-phényl)-prop-2-ynyl]-pip;;ridjn-3-yl}prop3n-î-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinin-1-yl) propyl] -1- [3- (3,5-bis-trifluoromethyl-phenyl) -prop-2-ynyl) -acid ] -pip ;; ridjn-3-yl} prop3n-I-oic acid

Acide (3R)4R)-3-{4-[3-(6-mcLboxyquiiiûIin-4-yi)propyl]-l-[3-(3,5-dimélhyl-phényl)-prop-2-ynylj-pipei idin-3 -yi} pro; >an- i -oique 2 5 Acide (3Ιζ4Ι<)-3- {4-[3-(6-mélhoxyqumoIin-4-yl)propyI]-1 -[3-(2,4-dichioro-6-méthyl- phényl)-prop-2-ynyl]-piperidin-3-yl} propan-1 -oique(3R) 4 R) -3- {4- [3- (6-Methyl-quinyl-4-yl) propyl] -1- [3- (3,5-dimethylphenyl) -prop-2-ynyl] -piperidine -3-yi} pro; (3Ιζ4Ι) -3- {4- [3- (6-methoxy-4-yl) propyl] -1- [3- (2,4-dichloro-6-methyl) -2-diol phenyl) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(thien-2-yl)-prop-2-ynyl]-piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) -prop-2-ynyl] -piperidin-3 acid -yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(5-chloro-thien-2-yl)-prop-2-30 ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (5-chloro-thien-2-yl) -prop-2-30-ynyl) -acid ] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl3-l-[3-(3-chloro-thien-2-yl)-prop-2-ynyl]-piperidin-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-thien-2-yl) -prop-2-ynyl] - acid piperidin-3-yl} propan-l-oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(5-méthyl-thien-2-yl)-prop-2-ynyl]-piperidin-3-yl}propan-l -oique 3 5 Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl-thien-2-yl)-prop-2- ynyl]-piperidin-3-yl}propan-1 -oique 120 22 114(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthien-2-yl) -prop-2-ynyl] acid [3R, 4R) -3- {4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl) -piperidin-3-yl} propan-1-ol -thien-2-yl) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic 120 22 114

Acide (3R,4R)-3-{4-[3-(6-niéthoxyquinolin-4-yl)propyl]-l-[3-(thien-3-yl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) -prop-2-ynyl] -piperidin-3 acid -yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin^l-yl)propyl]-1 -[3-( 1 -méthyl-pyrrol-2-yl)-prqp-2-ynyl]-piperidin-3-yl}prppan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-1-yl) propyl] -1- [3- (1-methyl-pyrrol-2-yl) -prop-2-ynyl] acid -piperidin-3-yl} prppan-1-oic

Acide (3R,4R>3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-( 1 -méthyl-pyrrol-3-yl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (1-methyl-pyrrol-3-yl) -prop-2-ynyl] - acid piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinoIin-4-yl)propyl]-l-[3-(thiazol-2-yl)-prop-2-ynyl]-piperidin-3-yl}prqpan-l -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinino-4-yl) propyl] -1- [3- (thiazol-2-yl) -prop-2-ynyl] -piperidin-3 acid -yl} prqpan-l -oic

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(thiazol-4-yl)-prop-2-ynyl]-piperidin-3-yl}propan-1-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (thiazol-4-yl) -prop-2-ynyl] -piperidin-3 acid yl} propan-1-oic acid

Acide (3R,4R)-3-{4-[3-(6-inéthoxyquinolin-4-yl)propyl]-l-[3-{thia2ol-5-yl>prop-2-ynyl]-piperidin-3-yl}propan- 1-oique(3R, 4R) -3- {4- [3- (6-Inethoxyquinolin-4-yl) propyl] -1- [3- {thia2ol-5-yl] prop-2-ynyl] -piperidin-3- acid yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(l-méthyl-imidazol-2-yl)-prop-2-ynyl]-piperidin-3-yl}propan- 1-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (1-methyl-imidazol-2-yl) -prop-2-ynyl] acid -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-niéthyl-imidazol-4-yI)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-imidazol-4-yl) -prop-2-ynyl] acid -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl-pyrazol-4-yl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-pyrazol-4-yl) -prop-2-ynyl] acid -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(oxazol-2-yl)-prop-2-ynyl]-piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) -prop-2-ynyl] -piperidin-3 acid -yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(oxazol-4-yl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-4-yl) -prop-2-ynyl] -piperidin-3 acid -yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(oxazol-5-yl)-prop-2-ynyl]-piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-5-yl) -prop-2-ynyl] -piperidin-3 acid -yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(6-méîhoxyquinolin-4-yl)propyl]-1 -[3-(pyridin-2-yl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) -prop-2-ynyl] -piperidin-3 acid -yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[3-(pyridin-3-yl)-prop-2-ynyl]-piperidin-3-yl } propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methyl-quinolin-4-yl) propyl] -1- [3- (pyridin-3-yl) -prop-2-ynyl] -piperidine -3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin^yl)propyl]-1 -[3-(pyridin-4-yl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolinyl) propyl] -1- [3- (pyridin-4-yl) -prop-2-ynyl] -piperidin-3-yl acid } propan-1 -oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-2-yl)-prop-2-ynyl]-piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) -prop-2-ynyl] -piperidin-3 acid -yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(6-méthdxyquinolin-4-yl)propyl]- l-[3-(pyrimidin-4-yl)-prop-2-ynyl]-piperidin-3-yl}propan-1-oique ‘(3R, 4R) -3- {4- [3- (6-Methylquinolin-4-yl) propyl] -1- [3- (pyrimidin-4-yl) -prop-2-ynyl] -piperidin-3 acid -yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-5-yl)-prop-2-ynyl]-piperidin-3-yl} propan-1 -oique 12 0 2 2 115(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-5-yl) -prop-2-ynyl] -piperidin-3-acid -yl} propan-1-oic 12 0 2 2 115

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin-4-yl)prqpyl]-l-[3-(pyrazm-2-yl)-prop-2-ynyl]-piperidin-3-yl}propan- 1-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyrazol-2-yl) -prop-2-ynyl] -piperidin-3 acid -yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(6-méthoxyquinolin^-yl)propyl]-l-[3-(pyrida2in-3-yl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-1-yl) propyl] -1- [3- (pyridin-3-yl) -prop-2-ynyl] -piperidin-3- acid yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(6-méthoxyqumolm-4-yl)propyl]-l-[3-(pyridazin-4-yl)-prop-2-ynyl]-piperidin-3-yl}propan-1-oique(3R, 4R) -3- {4- [3- (6-Methoxyqumol-4-yl) propyl] -1- [3- (pyridazin-4-yl) -prop-2-ynyl] -piperidin-3 acid yl} propan-1-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-phénylpropyl]piperidin-3-yl} propan- 1-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylpropyl] piperidin-3-yl} acid 1-propane

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-phénylbutyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4-phenylbutyl] piperidin-3-yl} acid propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)prqpyl]-l-[3-(2-fluoro-phényl)propyl]piperidm-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxy-iminolin-4-yl) propyl] -1- [3- (2-fluoro-phenyl) -propyl) -acid ] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-inéthoxyquinolin-4-yl)propyl]-l-[4-(2-fluoro-phényl)butyI]piperidm-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-fluoro-phenyl) butyl] acid ] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolm-4-yl)propyl]-l-[3-(3-fluoro-phényl)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyqumol-4-yl) propyl] -1- [3- (3-fluoro-phenyl) propyl) -acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méihoxyquinolin-4-yl)propyl]-l-[4-(3-fluoro-phényl)butyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-fluoro-phenyl) butyl] acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-inétho?iyquinolin-4-yl)propyl]-1 -[3-(4-fluoro-phényl)propyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-ethoxyquinyl-4-yl) propyl] -1 - [3- (4-fluoro-phenyl) - ) propyl] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(R,S>hydrox5,-3-(6-mé;hox>'quino’m-4-yl)propyl]-l-[4-(4-fluoro-phényl)butyl]piperidin-3-yl}propan-l"Oique(3R, 4R) -3- {4- [3- (R, S) -hydrox, -3- (6-methyloxy) -4-yl) propyl] -1- [4- 4-fluoro-phenyl) butyl] piperidin-3-yl} propan-l "oic acid

Acide (3R,4R)-3-{4-[3-(R7S) liydro?;y-3-(6-méthoxyc}iiiiiolin-4-yl){ïropyl]-l-[3-(2,3-difluoro-pbényl)propyl]piperidin-3-yl} propsn- 1-oique(3R, 4R) -3- {4- [3- (R7S)) -hydroxy-3 - ((6-methoxy) -benzyl-4-yl) -propyl] -1- [3- difluoro-pbenyl) propyl] piperidin-3-yl} prop-1-oic

Acide (3R,4R)-3- {4-[3-(R zS)-hydrox7-3-(6-méilioxyquinolin-4-yl)propyl]-1 -[4-(2,3-difluoro-phényl)butyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R 2 S) -Hydrox) -3- (6-methioxyquinolin-4-yl) propyl] -1- [4- (2,3-difluoro-phenyl) acid) butyl] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,6-difluoro-phényl)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (2,6-difluorophenyl) ) propyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(2,6-difluoro-phényl)butyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-difluoro-phenyl) acid ) butyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-chloro-phényl)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-phenyl) propyl] acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(2-chloro-phényl)butyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-chloro-phenyl) butyl] acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-chloro-phényl)propyl]piperidin-3-yl} propan-1 -oique •120 2 2 116(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-phenyl) propyl] -acrylic acid ] piperidin-3-yl} propan-1-oic • 120 2 2 116

Acide (3R,4R)-3- {4-[3-(R,S>hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(3-chloro-phényl)butyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-chlorophenyl) butyl] acid piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydioxy-3-(6-niélhoxyquinolin-4-yl)propyl]-1 -[3-(4-chloro-phényl)propyl]piperidin-3-yl }propan-1 -oique 5 Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(4-chloro- phényl)butyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-niethyloxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenyl) propyl) acid ] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -acetate 1- [4- (4-chlorophenyl) butyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,3-dichloro-phényl)prqpyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichlorophenyl) -acidic acid ) propyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[4-(2,3-dichloro-io phényl)butyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [4- (2,3-dichloro-io) -acid phenyl) butyl] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(2,6-dichloro-phényl)propyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (2,6-dichlorophenyl) -acidic acid ) propyl] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(RS)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(2,6-dichloro-phényI)butyl]piperidin-3-yl}propan-l-oique 15 Acide (3R4R)-3- {4-[3-(R,S)-h.ydroxy-3-(6-méthoxyquinolin-4-yl)propyll -1 -[3-(2-méthyl- ph«iyl)propyl]piperidiu-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-dichlorophenyl) butyl] acid ] (3R4R) -3- {4- [3- (R, S) -H.hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1-piperidin-3-yl} propan-1-ol [3- (2-methylphenyl) propyl] piperidin-3-yl} propan-1-ol

Acide (3R,4R)-3- {4-[3-(R,S)-bydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[4-(2-méthyl-phényl)butyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Bydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-methyl-phenyl) butyl] acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[5-(2-méthyl-20 pbényl)pentyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1 - [5- (2-methyl-pbenyl) acid pentyl] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[3-(3-métbyl-phényl)propyl]piperidin-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl) phenyl) ) propyl] piperidin-3-yl} propan-1-ol

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[4-(3-méthyl-phényl)butyl]piperidin-3 -yl }propan-1 -oique 2 5 Acide (3R,4R)-3- {4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-méthyl- phényl)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methyl-phenyl) butyl] acid ] (3R, 4R) -3- {4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1-piperidin-3-yl] propan-1-acid - [3- (4-methylphenyl) propyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-métboxyquinolin-4-yl)propyl]-1 -[4-(4-méthylphényl)butyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-metboxyquinolin-4-yl) propyl] -1- [4- (4-methylphenyl) butyl] piperidinic acid -3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]- l-[3-(2-méthoxy- 3 o phényl)propyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxy-3-phenyl) acid ) propyl] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-bydroxy-3-(6-métboxyquinolin-4-yl)propyl]-1 -[4-(2-méthoxy-phényl)butyl]piperidin-3 -yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -bydroxy-3- (6-metboxyquinolin-4-yl) propyl] -1- [4- (2-methoxy-phenyl) butyl acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthoxy-phényl)propyl]piperidin-3-yl}propan-l-oique ' 3 5 Acide (3R,4R)-3- {4-[3-(RS)-hydroxy-3-(6-méthoxyquinolin^-yl)propyl]-l -[4-(3-méthoxy-phényl)butyl]piperidin-3 -yl} propan-1 -oique 12 0 2 2 117(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxy-phenyl) propyl) -acid ] (3R, 4R) -3- {4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-2-yl) propyl] -l] -acid-3-yl} propan-1-ol - [4- (3-methoxy-phenyl) butyl] piperidin-3-yl} propan-1-oic 12 0 2 2 117

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-nié1hoxyqumolm-4-yl)propyl]-l-[3-(4-méthoxy-phényl)propyl]piperidm-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyphenyl) propyl] -1- [3- (4-methoxyphenyl) propyl] propyl] propyl] propyl] -propyl-3- (4-methoxyphenyl) propyl acid ] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(4-méthoxy-phényl)buiyl]piperidin-3-yl}propan-1 -oique 5 Acide (3R,4R)-3- {4-[3-(R,S)-hydro?cy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[3-(2-trifluoro- méthylphényl)propyl]piperidin-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-methoxyphenyl) buiyl acid ] (3R, 4R) -3- {4- [3- (R, S) -hydro-cy-3- (6-methoxyquinolin-4-yl) propyl] -piperidin-3-yl} propan-1-ol ] -1- [3- (2-trifluoromethylphenyl) propyl] piperidin-3-yl} propan-1-ol

Acide (3R,4R)-3-{4-[3-(R>S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-l-[4-(2-trifluoro-méthylphényl)butyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R) S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [4- (2-trifluoromethylphenyl) butyl] acid ] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolm-4-yl)propyl]-l -[3-(3-triiluoro-10 méthylphényl)propyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyqumol-4-yl) propyl] -1- [3- (3-trifluoromethylphenyl)) -acid propyl] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-<R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[4-(3-trifluoro-méthylphényl)butyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- <R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-trifluoromethylphenyl) butyl) acid ] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(R>S)-hydroxy-3-(6-mélhoxyquinolin-4-yl)propyl]-l-[3-(4-lrifluoro-méthylphényl)propyl]piperidin-3-yl}propan-l-oique 15 Acide (3R,4R>3- {4-[3<R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[4-(4-irifluoro- méthylphényl)butyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R) S) -hydroxy-3- (6-melhoxyquinolin-4-yl) propyl] -1- [3- (4-lrifluoro-methylphenyl) propyl) ] (3R, 4R) -3- (4- [3 R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1-piperidin-3-yl} propan-1-ol [4- (4-Irifluoromethylphenyl) butyl] piperidin-3-yl} propan-1-ol

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-phàiylthio-éthyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-phlthiothiethyl] piperidin-3 -ic acid yl} propan-1 -oic

Acide (3R,4R>3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[3-phénylthio-20 propyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylthio-propyl] piperidin-3- acid yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-mctboxyqumoliuA-yl)propyl]-l -[2-(2-fluoro-phénylthio)é;b.yl]piï>eï'idin-3-yI}prapan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methylboxymethyl-a) yl) propyl] -1- [2- (2-fluoro-phenylthio) b) acid; .yl] IIP> eï'idin-3-yl} Prapan-l-oic

Acide (3R/IR) 3-{4-[3-(R,S>hydroxy-3 (6-méthoxyquinolin-4-yl)propyl]-l-[3-(2-iluoro-phéi 4yîî1;ic>)pjj opyllpiy< idia-3-y)}propan-3-olque 2 5 Acide (3R54R) 3-{4 {3-(ï<S)-liy< lroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(3-fluoro- phénylthio)éthyl]piperidin-3-yl} propan-1 -oique(3R / IR) 3- {4- [3- (R, S) -hydroxy-3 (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluoro-phenyl) -bicyclo} (3R54R) 3- {4 {3- (N) -alkyl-3- (6-methoxyquinolin-4-yl) propyl-3-yl) propan-3-ol ] 1- [2- (3-fluorophenylthio) ethyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-iluoro-phénylthio)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-phenylthio) propyl) -acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(4-fluoro- 3 0 phénylthio)éthyl]piperidin-3-yl}propan- 1-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-fluorophenylthio) -acidic acid ) ethyl] piperidin-3-yl} propan-1-ol

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(4-fluoro-phénylthio)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluoro-phenylthio) propyl) -acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2,3-difluoro-phénylthio)éthyl]piperidin-3-yl} propan-1 -oique 35 Acide (3R,4R)-3-{4-[3-(R,S)-hydfOxy-’'-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,3-difluoro-phénylthio)propyl]piperidin- 3-yttëm -1-oique 120 2 2 118(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-difluoro-phenylthio) -acid ) ethyl] piperidin-3-yl} propan-1-oic acid (3R, 4R) -3- {4- [3- (R, S) -hydroxy) -2- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluoro-phenylthio) propyl] piperidin-3-ylm-1-yl 120 2 2 118

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2,6-difluoro-phényl±io)éthyl]piperidin-3-yl}propan- 1-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-difluoro-phenyl) acid ± io) ethyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S>hydroxy-3-(6-inéthoxyquinolin-4-yl)propyl]-l-[3-(2,6-difluoro-phényltbio)propyl]piperidin-3-yl}propan-1-oique 5 Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-l-[2-(2-chloro-phénylthio)éthyl jpiperidm-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluoro-phenylbio)) acid propyl] piperidin-3-yl} propan-1-oic acid (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquolin-4-yl) propyl] 1- [2- (2-Chloro-phenylthio) ethyl] -piperid-3-yl} -propan-1-ol

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-niéthoxyquinolin-4-yl)propyl]-1 -[3-(2-chloro-phénylthio)propyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-phenylthio) propyl] acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-liydroxy-3-(6-méîhoxyquinolin-4-yl)propyl]-l-[2-(3-chloro-10 phényltbio)éthyl]piperidin-3-yl}propan-1-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chloro-10-phenylbenzo) acid) ethyl] piperidin-3-yl} propan-1-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-chloro-phénylthio)propyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-phenylthio) propyl) ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méüioxyquinolin-4-yl)propylJ-1 -[2-(4-chloro-phénylthio)éthyl]piperidin-3-yl}propan-1 -oique 15 Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-n)é±oxyquinolin-4-yl)propyl]-1 -[3-(4-chloro- phényltbio)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (4-chloro-phenylthio) ethyl] acid piperidin-3-yl} propan-1-oic acid (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-n) ethoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenyltbio) propyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyI]-l-[2-(2,3-dichloro-phénylthio)éthyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-dichloro-phenylthio) -acid] ) ethyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,3-dichloro-2 o phénylthio)propyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (2,3-dichloro) -2-acid o phenylthio) propyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2,6-dichloro~phénylthio)éthyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (2,6-dichlorophenylthio) -acidic acid ) ethyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-l -[3-(2,6-dichloro-phénylthio)propyl]piperidin-3-yl }propan-1 -oique 2 5 Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2-méthyl- phénylthio)éthyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxy-iminolin-4-yl) propyl] -1- [3- (2,6-dichlorophenylthio) - ) propyl] piperidin-3-yl} propan-1-oic acid (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl)} propyl] -1- [2- (2-methylphenylthio) ethyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-méthyl-phénylthio)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methyl-phenylthio) propyl) acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-mé±ox>quinolin-4-yl)propyl]-1 -[2-(3-méthyl- 3 o phénylthio)éthyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methyl-quinolin-4-yl) propyl] -1- [2- (3-methyl) - (3R, 4R) -3- 3-phenylthio) ethyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl-phénylthio)propyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-phenylthio) propyl) -acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(4-méthyl- phénylthio)éthyl]piperidin-3-yl} propan-1 -oique 3 5 Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-méthyl- phénylîhio)propyl]piperidin-3-yl }propan-1 -oique 1 20 2 2 119(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (4-methylphenylthio) ethyl acid ] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] 3-piperidin-3-yl} propan-1-ol -1- [3- (4-methylphenylthio) propyl] piperidin-3-yl} propan-1-oic 1 20 2 2 119

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2-trifluoro-méth\dhénylthio)éthyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-trifluoromethyl) phenylthio) acid ) ethyl] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-trifiuro-méthydphénylthio)propyl]piperidin-3-yl}propan-l-oique 5 Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[2-(3-trifluoro- méth\'lhénylthio)éthyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifuro-methylphenylthio) propyl) acid ] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyqumolin-4-yl) propyl] -acetate] 1- [2- (3-Trifluoromethylphenylthio) ethyl] piperidin-3-yl} propan-1-ol

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-trifluro-méth\iphénylthio)propyl]piperidin-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluro-methyl) phenylthio) acid ) propyl] piperidin-3-yl} propan-1-ol

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)prqpyl]-l-[2-(4-trifluoro-10 méthylhénylthio)éthyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-trifluoromethyl) methyl) thio) ethyl] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méÛioxyquinolin-4-yl)propyl]-l-[3-(4-trifluro-méthylphénylthio)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methyloxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenylthio) propyl) ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2-méthoxy-phénylthio)éthyl]piperidin-3-yl} propan-1 -oique 15 Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3 -(2-méthoxy-phényhhio)propyl]piperidin-3-yl}prqpan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methoxy-phenylthio) ethyl acid ] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -acetate 1- [3- (2-methoxy-phenylthio) propyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-l-[2-(3-méthoxy-phénylthio)éibyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquolin-4-yl) propyl] -1- [2- (3-methoxyphenylthio) eibyl) ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-A-yl)propyl]-1 -[3-(3-méthoxy- 2 o phén>ithio)propyl]piperidm-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-A-yl) propyl] -1- [3- (3-methoxy-2-phenyl) -acidic acid; > ithio) propyl] piperidm-3-yl} propan-1-oic

Acide (3R/?R)-3- {4-[3 · (R,S)-hydroxy- 3-(6-méthœyquinolin-4-yl)propyl]-l -[2-(4-méihoxy-phénylthio) é&amp;yl]piperidin-3 -yl} propai )-1 -oique(3R / R) -3- {4- [3 · (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (4-methoxyphenylthio) acid) e) yl] piperidin-3-yl} propai) -1 -oic

Acide (3R,4R)-3- {4-f 3-(RîS)-hydroxy-3-(6 -métho^quinoLin-4 -yl)propyl]~ 1 -[3-(4-méthoxy-phénylib io)pro1 yl] pipsodiu-3 -y 1} propai ι-1 -oique 25 Acide (3R,4R)-3-{4-[3-(R,S)-liydroxy-3-(6-xnétlioxyquinolin-/i-yl)propyl]-l-[cyclopiOpyl-méthyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4-[3- (R) S) -hydroxy-3- (6-methoxyphenyl-4-yl) propyl] -1- [3- (4-methoxy-phenylbio) acid) pro1 yl] pipsodiu-3-yl} propai-1-oic Acid (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-x-tolyloxyquinoline) yl) propyl] -1- [cyclopiperyl-methyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propylf-1 -[2-(cyclopropyl)éthyl jpiperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopropyl) ethyl] piperidin-3-yl acid } propan-1 -oic

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[cyclobutyl-30 méthyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclobutyl-30-methyl] piperidin-3-yl acid } propane-l-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(cyclobutyl)éthyl ]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclobutyl) ethyl] piperidin-3 acid -yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[cyclopentyl-méthyl]piperidin-3-yl}propan-1 -oique 3 5 Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -f2-(cyclopentyl) éthyl]piperidin-3-yl}propan-1 -oique 120 2 2 120(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [cyclopentylmethyl] piperidin-3-yl} acid propan-1-oic acid (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 -f- (cyclopentyl) ) ethyl] piperidin-3-yl} propan-1-oic 120 2 2 120

Acide(3R,4R)-3-{4-[3-(R,S>hydroxy-3-(6-méÎhoxyquinolm-4-yl)propyl]-l-[cyclohexyl- méihyl]piperidin-3-yi}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [cyclohexylmethyl] piperidin-3-yl} propanic acid -l-oic

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méîhoxyquinolin-4-yl)propyl]-l -[2-(cyclohexyl)éthyl]piperidin-3-yl}propan-l-oique 5 Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoIin-4-yl)propyl]-l-[2-(cyclopropyl-thio)éthyl]piperidin-3-yl}prqpan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidin-3-acid (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-yl] propan-1-yl - (cyclopropylthio) ethyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquino]in-4-yl)propyl]-1 -[3-(cyclopropyl-thio)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquino) -4-yl) propyl] -1- [3- (cyclopropylthio) propyl) acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(cyclobutyl-io thio)éthyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclobutyl-10thio) ethyl] acid piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(cyclobutyl-thiopropyl]piperidin-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (cyclobutyl-thiopropyl) piperidin-3 acid -yl} propan-l-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[2-(cyclopentyl-thio)éthyl]piperidin-3-yl}propân-1 -oique 15 Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -{3-(cyclopentyl-thio)propyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidinic acid -3-yl} propan-1-oic acid (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- {3- (cyclopentylthio) propyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(cyclohexyl-thio)éthyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl-thio) ethyl] piperidine acid -3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(cyclohexyl-2 o thio)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclohexyl) -2-thio) propyl acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-méthylthio-éthyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2-methylthio-ethyl] piperidin-3- acid yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-l-[3-méthylthio-propyl]piperidin-3-yl}propan-l -oique 2 5 Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-éthyltbio- éthyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [3-methylthio-propyl] piperidin-3- acid (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-yl] propan-1-yl ethyltbioethyl) piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-éthylthio-propyl]piperidin-3-yl } propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-ethylthio-propyl] piperidin-3- acid yl} propan-1 -oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(n-propylÎhio)30 éthyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (n-propylthio) ethyl] acid piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(n-propylîhio)propyl]piperidin-3 -yl} propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (n -propyl) thio) propyl] piperidine -3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,5)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(n-butylthio)éthyl]piperidin-3-yl}propdn-l -oique 3 5 Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(n-butylthio) propyl]piperidin-3-yl}propan-1 -oique 120 2 2 121(3R, 4R) -3- {4- [3- (R, 5) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (n-butylthio) ethyl] piperidinic acid (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1,3-diol-3-yl} propan-1-yl - [3- (n-butylthio) propyl] piperidin-3-yl} propan-1-oic 120 2 2 121

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yî)propyl]-l-[3-(thien-2-yl)propyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) propyl) acid ] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[4-(thien-2-yl)butyijpiperidm-3-yl}propan-1 -oique 5 Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-inéthoxyquinolin-4-yl)propyl]-1 -[2-(thien-2-yl) ihioéthyl]piperidm-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-2-yl) butyl] piperidin acid -3-yl} propan-1-oic acid (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperid-3-yl} propan-1-ol

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thien-2-yl)thiopropyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) thiopropyl) acid ] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(5-cbloro-10 thien-2-yl)propyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-c-10-chlorothienic acid) acid; 2-yl) propyl] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(5-chloro-thien-2-yl)butyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [4- (5-chloro-thien-2) -acidic acid yl) butyl] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-médioxyquinolin-4-yl)propyl]-l-[2-(5-chloro-thien-2-yl)thioéthyl]piperidin-3-yl}propan-1 -oique » 15 Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]- l-[3-(5-chloro-thien-2-yl)thiopropyl]piperidm-3-yl}propan-l Oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-medioxyquinolin-4-yl) propyl] -1- [2- (5-chloro-thien-2) -acidic acid (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl} propan-1-yl) yl) propyl] -1- [3- (5-chloro-thien-2-yl) thiopropyl] piperid-3-yl} propan-1-ol

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoIin-4-yl)propyl]-l-[3-(3-chloro-thien-2-yl)propyl]piperidm-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-thien-2) -acidic acid yl) propyl] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-inéthoxyquinolin-4-yl)propyl]-1 -[4-(3-chIoro-2 o thien-2-yl)buiyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-chloro-2-thien) acid -2-yl) buiyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-bydro^-3~(6-méthoxyquInoIiii-4-y!)propyl]-l-[2-(3-cliloro-Ùiien-2-yl)thioéÛiyi]pij >cridin-3-yl}proj ian-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Bydro-3 - [(6-methoxy-quinyl-4-yl) propyl] -1- [2- (3-chloro-Ⓒ) acid -2-yl) thioeryl] pij> cridin-3-yl} proj ian-1-oic

Acide (3R,4R)-3- {4-[3· (R,S) hydroxy-3-(6-niéîhoxyqumolm~4-yl)piOpylj-1 -[3-{3-chloro-thien-2-yî)thiopropyi]piperidin-3-yl}propan-1 -oique 2 5 Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-métboxyquinoiin-4-yl)propyl]-1 -[3-(5-méthyl - thien-2-yl)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3 · (R, S) -hydroxy-3- (6-naphthoxy-4-yl) p-propyl] -1- [3- {3-chloro-thien-2-yl] acid; Thiopropylpiperidin-3-yl} propan-1-oic acid (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-metboxyquinin-4-yl)) propyl] -1- [3- (5-methylthien-2-yl) propyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(5-méthyl -thien-2-yl)butyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [4- (5-methylthien-2) -acidic acid -yl) butyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(5-méthyl - 3 o thien-2-yl)thioéthyl]piperidm-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (5-methyl) -3-thienoic acid -2-yl) thioethyl] piperid-3-yl} propan-1-ol

Acide (3R,4R)-3- {4-[3-(RS)-hydroxy-3-(6-méthoxyqumolki-4-yl)propyl]-1 -[3-(5-méthyl -thien-2-yl)ÎhiopropylJpiperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (RS) -hydroxy-3- (6-methoxyqumol-4-yl) propyl] -1 - [3- (5-methyl-thien-2-yl) -acid ) Isopropyl-piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin^-yl)propyl]-1 -[3-(3-méthyl -thien-2-yl)propyl]piperidin-3-yl} propan-1 -oique 3 5 Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(3-méthyl - thien-2-yl)butyl3piperidin-3-yl}propan-l-oique 120 22 122(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-1-yl) propyl] -1 - [3- (3-methyl-thien-2-yl) -acetate yl) propyl] piperidin-3-yl} propan-1-oic acid (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) ) propyl] -1- [4- (3-methylthien-2-yl) butyl] -piperidin-3-yl} propan-1-oic 120 22 122

Acide (3R4R>3-{4-[3-(R,S>hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(3-méthyl -thien-2-yl)thioéthyl]piperidm-3-yl}propan-1 -oique(3R4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methyl-thien-2-yl) thioethyl) acid ] piperidm-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-bydroxy-3-(6-métiioxyquinolin-4-yl)propyl]-l-[3-(3-méthyl -thien-2-yl)thiopropyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -bydroxy-3- (6-methioxyquinolin-4-yl) propyl] -1- [3- (3-methylthien-2) -acidic acid -yl) thiopropyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thien-3-yl)propyl]piperidm-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) propyl) -acrylic acid ] piperidm-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyqiiinolin-4-yl)propyl]-1 -[4-(thien-3-yl)butyl]piperidin-3-yl}propan-1-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-3-yl) butyl] acid ] piperidin-3-yl} propan-1-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méüioxyquinolin-4-yl)propyl]-1 -[2-(thien-3-yl)thioéthyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxoquinolin-4-yl) propyl] -1- [2- (thien-3-yl) thioethyl acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R3)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thien-3-yl)thiopropyl]piperidm-3-yl}prqpan-1 -oique(3R, 4R) -3- {4- [3- (R3) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) thiopropyl] piperidm acid -3-yl} prqpan-1 -oic

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-l-[3-(fur-2-yl)propyl]piperidin-3-yl }propan-1-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (fur-2-yl) propyl acid ] piperidin-3-yl} propan-1-oic

Acide (3R_4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]- l-[4-(fur-2-yl)butyl]piperidin-3-yl}propan-1 -oique(3R_4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [4- (fur-2-yl) butyl] piperidine acid -3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S) hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(iùr-2-yl)thioéthyl]piperidin-3-yl}propan-l oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1H-2-yl) thioethyl] acid piperidin-3-yl} propan-l oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(fur-2-yl)thiopropyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (fur-2-yl) thiopropyl acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S>hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(fiir-3-yl)propyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-yl) propyl] -acrylate piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[4-(far-3-yl)butyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxy-iminolin-4-yl) -propyl] -1 - [4- (far-3-yl) -butyl acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[2-(fur-3-yl)thioéthyl]piperidin-3-yl}propan-1 oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (fur-3-yl) thioethyl) acid ] piperidin-3-yl} propan-1ic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-{fiir-3-yl)thiopropyl]piperidin-3-yl}propan-1 oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-yl] -3-yl) thiopropyl acid ] piperidin-3-yl} propan-1ic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 - [3 -( 1 -méthyl-pyirol-2-yl)propyl]piperidin-3-yl }propan-1 oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3 - (1-methyl-pyirol-2) -acidic acid -yl) propyl] piperidin-3-yl} propan-1ic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-( 1 -méthyl-pyiTol-2-yl)butyl]piperidin-3-yl}propan-1 oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [4- (1-methyl-pyiTol-2) -acidic acid -yl) butyl] piperidin-3-yl} propan-1-ol

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-( 1 -méthyl-pyrrol-2-yl)thioéthyl]piperidin-3-yl}propan-l oique ’(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (1-methyl-pyrrol-2) -acid -yl) thioethyl] piperidin-3-yl} propan-lolic acid

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 - [3-( 1 -méthyl-pyrrol-2-yl)thiopropyl]piperidin-3-yl }propan-1 oique 12 0 2 2 123(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (1-methyl-pyrrol-2) -acid -yl) thiopropyl] piperidin-3-yl} propan-1ic acid 12 0 2 2 123

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[3-( 1 -méthyl-pyrrol-2-yl)propyl3piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (1-methyl-pyrrol-2) -acid -yl) propylpiperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4'yl)propyl]-1 -[4-( 1 -méüiyl-pyrrol-3-yl)butyl]piperidin-3-yl}propan-l-oique 5 Acide (3R,4R)-3- {4-[3-(R,S)-hydF0xy-3-(6-inéthoxyquinolin-4-yl)propyl3-1 -[2-( 1 -méthyl- pyrrol-3-yI)thioéthyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxy-iminolin-4-yl) propyl] -1 - [4- (1-methyl-pyrrol-3) -acid -yl) butyl] piperidin-3-yl} propan-1-oic acid (3R, 4R) -3- {4- [3- (R, S) -hydFoxy-3- (6-methoxyquinolin-4-yl) ) propyl3-1 - [2- (1-methylpyrrol-3-yl) thioethyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)prqpyi]-1 -[3-( 1 -mélhyl-pyrrol-3-yl)thiopropyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (1-methyl-pyrrol-3) -acid -yl) thiopropyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(thiazol-2-10 yl)propyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazol-2-yl) acid) propyl] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(tibiazol-2-yl)butyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (tibiazol-2-yl) butyl] acid ] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[2-(thiazol-2-yl)thioéthyl]piperidin-3-yl}propan-l-oique 15 Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[3-(thiazol-2- yl)thiopropyl]piperidin-3-yl}proparx-l -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (thiazol-2-yl) thioethyl acid ] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -acetate] 1- [3- (Thiazol-2-yl) thiopropyl] piperidin-3-yl} propar-1-ol

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(l-mélhyl-irnidazol-2-yl)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-melhyl) imidazol) -acid -yl) propyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[4-(l -méthyl- 2 o imidazol-2-yl)butyl]pipeîidm-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquolin-4-yl) propyl] -1- [4- (1-methyl) imidazol acid -2-yl) butyl] piperid-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-ïnéthoxyiiumolm-4-y3)propyl]-l-[2-(l-méthyl-ixnidazol-2-yî)ihioétbyl]pipcridin-3-yi}piOpaii-l-oïque(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxy-iolol-4-yl) propyl] -1- [2- (1-methyl-ixnidazol-2) -acidic acid; -YI) ihioétbyl] pipcridin-3-yl} piOpaii-l-oic

Acide (3R;4R)-3- {4-Γ3-(R,S)-hydroxy 3-(ô-ni:3.boxyquinolin-4-yI)propyl]-l -[3-( 1 -méthyl-imidazol-2-yI)ibiopropyî]pii «ridin- 3-yl} j tropan-1 -oique 25 Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méîhoxyquinolin-4-yl)propyl]-l-[3-(3-inéthyl-imidazol-4-yl)propyl]piperidin-3-yl}propan-l-oique(3R; 4R) -3- {4-Γ3- (R, S) -hydroxy-3- (6-ni-: 3 -boxyquinolin-4-yl) propyl] -1 - [3- (1-methylimidazole) acid 2- (1-yl) -biopyryl) -propyl-3-yl} tropan-1-oic acid (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- méîhoxyquinolin-4-yl) propyl] -l- [3- (3-inéthyl-imidazol-4-yl) propyl] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(3-méthyl-imidazol~4-yl)butyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [4- (3-methyl-imidazole) -4 -yl) butyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyI]-1 -[2-(3-méthyl- 3 o imidazol-4-yl)thioéthyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methyl) imidazol acid -4-yl) thioethyl] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(3-méthyl-imidazol-4-yl)thioprûpyl]piperidm-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1 - [3- (3-methyl-imidazol) -4-acid yl) thioprûpyl] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-méthyl-pyrazoî-4-yl)propyi]piperidin-3-yl}propan-l-oique 3 5 Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(3-méthyl- pyrazo3-4-yl)butyl]piperidin-3-yl }propan-1 -oique ‘120 2 2 124(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-pyrazol) -4-acid -yl) propyl] piperidin-3-yl} propan-1-oic acid (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4- yl) propyl] -1- [4- (3-methyl-pyrazol-4-yl) butyl] piperidin-3-yl} propan-1-oic '120 2 2 124

Acide (3R,4R)-3-{4-[3-(R,S)-hydioxy-3-(6-niéthoxyqumolin-4-yl)propyl]-l-[2-(3-méthyl-pyrazol-4-yl)thioéthyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxy-4-yl) propyl] -1- [2- (3-methyl-pyrazol) -4-acid yl) thioethyl] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3<R,S>hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl-pyrazol-4-yl)tbioprqpyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3 R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-pyrazol-4-yl) acid ) tbioprqpyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R>3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(oxazol-2-yl)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) propyl] acid piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(oxazol-2-yl)buîyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (oxazol-2-yl) methyl) acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(oxazol-2-yl)thioéthyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (oxazol-2-yl) thioethyl acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méüioxyquinolin-4-yl)propyl]-l-[3-(oxazol-2-yl)thiopropyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methioquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) thiopropyl) acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[3-(pyridin-2-yl)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinin-4-yl) propyl] -1- [3- (pyridin-2-yl) propyl) -acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)- hydroxy-3-{6-méthoxyquinolin-4-yl)propyl]-1 -[4-(pyridin-2-yi)butyl]p;peridin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-2-yl) butyl] acid ] peridin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[2-(pyridin-2-yl)thioéthyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (pyridin-2-yl) thioethyl acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridin-2-yl)thiopropyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (pyridin-2-yl) thiopropyl acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridin-3-yl)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl) propyl) acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[4-(pyridin-3-yl)butyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [4- (pyridin-3-yl) butyl] acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyridin-3-yl)thioéthyl]piperidin-3 -yl} propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (pyridin-3-yl) thioethyl acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[3-(pyridin-3-yl)thiopropyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (pyridin-3-yl) thiopropyl acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]- l-[3-(pyridin-4-yl)propyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl) propyl] acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- [4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(pyridin^l-yl)butyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- [4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-1-yl) butyl] acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[5-(pyridin-4-yl)pentyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [5- (pyridin-4-yl) pentyl acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyridin-4-yl)thioéthyl]piperidin-3-yl }propan-1 -oique 120 2 2 125(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (pyridin-4-yl) thioethyl acid ] piperidin-3-yl} propan-1-oic 120 2 2 125

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[3-(pyridin-4-yl)tiiiopropyl}piperidin-3-yl}propan-1-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (pyridin-4-yl) tiiopropyl acid } piperidin-3-yl} propan-1-oic acid

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-{pyriinidin-2-yl)propyl]piperidin-3-yl}propan-l-oique 5 Acide (3R,4R)-3- {4-[3-(RS)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[4-(pyrimidin-2-yl)butyl]piperidin-3-yl}propan- 1-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-pyrimidin-2-yl) propyl acid ] (3R, 4R) -3- {4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1-piperidin-3-yl} propan-1-ol [4- (pyrimidin-2-yl) butyl] piperidin-3-yl} propan-1-ol

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-niéthoxyquinolin-4-yl)propyl]-l-[2-(pyriinidin-2-yl)thioéthyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyriinidin-2-yl) thioethyl acid ] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-inéthoxyquinolin-4-yl)propyl]-l-[3-(pyrixnidm-2-10 yl)thiopropyl]piperidin-3-yl}propan- 1-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrixnidm-2-10yl) acid) thiopropyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l -[3-(pyrimidin-4-yl)propyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-4-yl) propyl) -acrylic acid ] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-inéthoxyquinolin-4-yl)propyl]-l-[4-(pyiimidin-4-yl)butyl]piperidin-3-yl}propan-l -oique 15 Acide (3R,4R)-3- {4-[3-(RS)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-l -[2-(pyrimidin-4-yl)thioéthyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyiimidin-4-yl) butyl] acid ] (3R, 4R) -3- {4- [3- (RS) -hydroxy-3- (6-methoxy-iminolin-4-yl) -propyl] -1-propan-1-yl [2- (pyrimidin-4-yl) thioethyl] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-4-yl)thiopropyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-4-yl) thiopropyl acid ] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-5-20 yl)propyl]piperidin-3-yl}propan-1-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (pyrimidin-5-yl) acid propyl] piperidin-3-yl} propan-1-oic acid

Acide (3K,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méihoxyquinolin-4~yl)propyl]-l-[4-(pyrimidin-5-y l)butyl ]piperidin-3 -y 1} propan-1 - oique(3K, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidin-5-yl) butyl} acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-{R,S>}iy‘roxy-3<6-méiboxyquinolin-4-yl)pîOpyl]-l-[2"(pyrimidm-5’ yl)thioéihyi]pipcndm-3-yl}propan-l-oique 2 5 Acide (3R,4R)- 3- {4-[3-(R,S}-hydioxy-3-(6-xnéthoxyquiÎÎolin-4-yl)propyl]-1 -[3-(pyrimidin-5yl)thiopropyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -3-hydroxy-6-meiboxyquinolin-4-yl) -p-butyl] -1- [2 - (pyrimidin-5-yl) acid) [(R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquiolin-4-yl) propyl) -2- [4- [3- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl) -2- [(3R, 4R) -3-yl} propan-1-yl) ] -1- [3- (pyrimidin-5yl) thiopropyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méûioxyquinolin-4-yl)propyl3-1 -[3-(pyrazin-2-yl)propyl]piperidin-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methyloxyquinolin-4-yl) propyl] -1 - [3- (pyrazin-2-yl) propyl] acid piperidin-3-yl} propan-l-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(pyrazin-2-30 yl)butyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [4- (pyrazin-2-yl) acid butyl] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-métiioxyquinolin-4-yl)propyl]-l -[2-(pyrazin-2-yl)thioéthyl]piperidin-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methioxyquinolin-4-yl) propyl] -1 - [2- (pyrazin-2-yl) thioethyl acid ] piperidin-3-yl} propan-l-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrazin-2-yl)thiopropyl]piperidin-3-yl}propan-1 -oique 35 Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(pyridazin-3·yl)propyl]piperidin- 3-yl} propan-1 -oique 120 2 2 126(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) thiopropyl acid ] (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -acetate 1- [3- (pyridazin-3-yl) propyl] piperidin-3-yl} propan-1-oic 120 2 2 126

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-<6-méthoxyquinolin-4-yl)prq3yl]-l-[4-(pyrida2in-3-yl)butyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-3-yl) butyl] -acetate ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyridazin-3-yl)îbioéthyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridazin-3-yl)} -bioethyl acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridazin-3-yl)thiopropyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) thiopropyl acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-rnéthoxyquinolin-4-yl)propyl]-1 -[3-(pyridazin-4-yl)propyl]piperidin-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4-yl) propyl] acid ] piperidin-3-yl} propan-l-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[4-(pyridazm-4-yl)butyl]piperidin-3-yl}propan-1-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [4- (pyridazm-4-yl) butyl] acid ] piperidin-3-yl} propan-1-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyridazm-4-yl)thioéthyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (pyridazm-4-yl) thioethyl acid ] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridazin-4-yl)thiopropyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4-yl) thiopropyl acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthüxyquinolin^-yl)propyl]-1 -[3-phényl-prop-2 -ynyl]-piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methylquinolin-1-yl) propyl] -1- [3-phenyl-prop-2 -ynyl] - acid piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydrox>;-3-(6-méthoxyquinolin-4-yl)prüpyl]-1 -[3-(2-fluoro-phényl)-prop-2-yny]]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydrox) -3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluoro-phenyl) - (3- ) -prop-2-ynyl]] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-fluoro-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-fluoro-phenyl) - acid prop-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-fluoro-phényl)-prop-2-ynyl]-piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (4-fluoro-phenyl) - acid prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-chloro-phényl)-prop-2-ynyl]-piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (2-chloro-phenyl) - acid prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {^[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-l -[3-(3-chloro-phényl)-prop-2-ynyl]-piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {[[3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1 - [3- (3-chloro-phenyl) prop) acid -2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R.4R)-3- {4-[3-(RS)-hydroxy-3-(6-mélhoxyqumolin-4-yl)propyl]-1 -[3-(4-ch]oro-phényl)-prop-2-ynyl]-piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (RS) -hydroxy-3- (6-methoxy-4-yl) -propyl] -1- [3- (4-chloro-phenyl) phenyl) - prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(RS)-hydroxy-3-(6-méthoxyqumoiin-4-yl)propyl]-1 -[3-(2-méthyl-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (RS) -hydroxy-3- (6-methoxy-4-yl) -propyl] -1 - [3- (2-methyl-phenyl) -propyl] -acrylic acid; 2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R.4R)-3- {4-[3-(RS)-hydroxy-3-(6-méthoxyqumolm-4-yl)propyl]-1 -[3-(3-méthyl-phényl)-prop-2-ynyl]-piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (RS) -hydroxy-3- (6-methoxyqumol-4-yl) propyl] -1 - [3- (3-methyl-phenyl) propyl] -acrylic acid; 2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin^-yl)propyl]-1 -[3-(4-méthyl-phényl)-prop-2-ynyl]-pipefidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-1-yl) propyl] -1 - [3- (4-methylphenyl) prop) acid -2-ynyl] -pipefidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-trifluoro- méthyl-phényl)-prop-2-ynyl]-piperidin-3-yl} propan-1 -oique 12022 127(3R, 4R) -3- {4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethyl-phenyl) - prop-2-ynyl] -piperidin-3-yl} propan-1-oic 12022 127

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoIiii-4-yl)propyl]-1 -[3-(3-trifluoro-méthyi-phényl)-prop-2-ynyl]-piperidin-3-yl}prqpan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinyl) -4-yl) propyl] -1- [3- (3-trifluoromethyl) phenyl) -acrylic acid ) -prop-2-ynyl] -piperidin-3-yl} prqpan-l-oic acid

Acide (3R,4R)-3- {4-[3-(RS)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(4-trifluoro-méthyl-phényl)-prop-2-ynyl]-piperidiD-3-yl}propan-l-oique 5 Acide (3R,4R>3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)prqpyl]-l-[3-(2-méÛioxy-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (RS) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (4-trifluoromethyl-phenyl) - prop-2-ynyl] -piperidin-3-yl} propan-1-oic acid (3R, 4R) -3- [4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4- yl) prqpyl] -l- [3- (2-méÛioxy-phenyl) -prop-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R.S)-hydroxy-3“(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthoxy-phényl)-prop-2-ynyl]-piperidm-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (RS) -hydroxy-3 - (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxy-phenyl) -propyl] -acrylic acid; 2-ynyl] -piperidm-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(RÎS)-hydroxy-3-(6-inéthoxyqum.olm-4-yl)propyl]-1 -[3-(4-méthoxy-io phényl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-ethoxy-immol-4-yl) propyl] -1 - [3- (4-methoxy-10-phenyl) -acidic acid) -prop-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-mé1hoxyquinolin-4-yl)propyl]-1 -[3-(3,4-difluoro-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4-difluorophenyl) ) -prop-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2J4-difluoro-phényl)-prop-2-ynyl]-piperidm-3-yl}propan-l-oique 15 Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin4-yi)propyl]-l-[3-(3,4-dichIoro-phàiyl)-prop-2-ynyl]-piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-difluoro-phenyl)) - Prop-2-ynyl] -piperidin-3-yl} propan-1-oic acid (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) ) propyl] -1- [3- (3,4-dichloro-phenyl) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,3-dichloî‘o-phàiyl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichloride) acid, -phàiyl) -prop-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,4-dichloro- 2 0 phényl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (2,4-dichloroacid) acid 0 (phenyl) -prop-2-ynyl] -piperidin-3-yl} propan-1-ol

Acjde(3R,4R)-3-{4 [3-(R,S)-hydroxy-3-(6-méiboxyfjuiuolm-4-yî)propyi]-l-[3-(2,4,6-trichloro -phényl)-prop-2-yiiyl]-pipa'id' * ι -3-yl} p; opan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxy-4-yl) propyl] -1- [3- (2,4,6-trichloro) -acetate; phenyl) -prop-2-ylyl] -piperidol-3-yl} p; opan-1 -oic

Acide (31<4R)-3-{4-[3-(i<S)-hydroxy-3-(6 métboxyquiuolin-d-yOpropylj-l-iS-ÎS^S-dichlorœphényl)-r>rop-2.-yn iy3]-pipa klùt-3-y!} propau-1 - oique 25 Acide(3 ,4R)-3-{4-[3-(R,S)-hydfoxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(4-chloro-3-fluoro-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3 R) -3- {4- [3- (1-S) -hydroxy-3- (6-metboxyquinolin-4-ylpropyl-1-yl) -5-dichloro-phenyl) -r-rop-2-acid. (3, 4R) -3- {4- [3- (R, S) -hyd -oxy-3- (6-methoxyquinolin-4-yl) -propa-3-yl) -yl) propyl] -1- [3- (4-chloro-3-fluoro-phenyl) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-niéthoxyquinolin-4-yl)propyl3-1 ~[3-(3-chloro-4-fluoro-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-4-fluorophenyl) -acrylic acid) phenyl) -prop-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(RS)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-chloro-4- 3 0 fluoro-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4-fluoro) acid -phenyl) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-chloro-5-fluoro-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-5-fluoro) acid phenyl) -prop-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(RS)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-chloro-2-fluoro-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique 3 5 Acide (3R,4R)-3- {4-[3-(RS)-hydroxy-3-(6-mé{hoxyqumoIin-4-yl)propyl]-1 -[3-(3-fluoro-4-méthyl-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique 120 2 2 128(3R, 4R) -3- {4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-2-fluoro-phenyl) acid ) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic acid (3R, 4R) -3- {4- [3- (RS) -hydroxy-3 (6-methyl)} Hoxy-quinolin-4-yl) propyl] -1- [3- (3-fluoro-4-methyl-phenyl) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic 120 2 128

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(4-chloro-3- trifluorométhyl-phényl)-prop-2-ynyl]-piperidm-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3-trifluoromethyl) -acidic acid; phenyl) -prop-2-ynyl] -piperidm-3-yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(R,S>-hydroxy-3-(6-méthoxyquinoiin-4-yl)propyl]-l-[3-(2-chloro-4- trifluorométhyl-phényl)-prop-2-ynyl]-piperidin-3-yi}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4-trifluoromethyl) acid, -phenyl) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R>3- {4-[3-(R,S>hydroxy-3-<6-méîhoxyqumolin-4-yl)propyl]-l -[3-(2-chloro-5- trifluorométhyl-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxy-4-yl) -propyl] -1- [3- (2-chloro-5-trifluoromethyl-phenyl) -acrylic acid ) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(5-chloro-2- méthoxy-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (5-chloro-2-methoxy) -acidic acid phenyl) -prop-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(R,S>hydroxy-3-(6-mé±oxyquinolin-4-yl)propyl]-l-[3-(3,5-bis- triiluorométhyl-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-bis) -acrylate) triiluorométhyl-phenyl) -prop-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3,5-diméthyl- phényl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-dimethylphenyl) -acrylic acid; ) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,4-dichloro- 6-méthyl-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oiqueAcide (3R,4R)-3- {4-[3-(R,S)-hydrox\'-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(thien-2-yl)-prop-2 -ynyl]-piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-dichloroacetic acid) acid 6 Methyl-phenyl) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic Acid (3R, 4R) -3- {4- [3- (R, S) -hydroxyl] -3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2 -ynyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(5-chloro-thien-2-yl)-prop-2-ynyl]-piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chloro-thien-2) -acidic acid -yl) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-chloro-thien-2-yl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-thien-2) -acid yl) -prop-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(5-méthyl-thien-2-yl)-prop-2-ynyl]-piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (5-methyl-thien-2-yl) -acid ) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl-thien-2-yl)-prop-2-ynyl]-piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-methylthien-2) -acidic acid -yl) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-mélhoxyquinolin-4-yl)propyl]-1 -[3-(thien-3-yl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-melhoxyquinolin-4-yl) propyl] -1 - [3- (thien-3-yl) - acid prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-mé±oxyquinolin^-yl)propyl]-1 -[3-( 1 -méthyl-pyrrol-2-yl)-prop-2-ynyl]-piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-1-yl) propyl] -1- [3- (1-methylpyrrol) -acrylic acid; 2-yl) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-( 1 -méthyl-pyrrol-3-yl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (1-methyl-pyrrol-3) -acid -yl) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {•4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(thiazol-2-yl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {• 4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazol-2-yl) acid -prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(thiazol-4-yl)-prop-2-ynyl]-piperidin-3-yl} propan-1 -oique ’(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (thiazol-4-yl) - acid prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(thiazol-5-yl)- prop-2-ynyl]-piperidin-3-yi }propan-1 -oique 12 0 2 2 129(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (thiazol-5-yl) - acid prop-2-ynyl] -piperidin-3-yl} propan-1-oic 12 0 2 2 129

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-( 1 -méthyl-imidazol-2-yl)-prop-2-ynyl3-piperidm-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1 - [3- (1-methyl-imidazol-2) -acidazol yl) -prop-2-ynyl3-piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-niéthyl-imidazol-4-yl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique 5 Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-méthyl-pyrazol^-yl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-methylimidazole) -4-acid 2-ynyl] -piperidin-3-yl} propan-1-oic acid (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-allyl)} -méthoxyquinolin-4-yl) propyl] -l- [3- (3-methyl-pyrazol ^ -yl) -prop-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-niéihoxyquinoIin-4-yl)propyî]-l-[3-(oxa2)ol-2-yl)-prop-2-ynyl]-piperidm-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methylene-4-yl) propyl] -1- [3- (oxa) -yl) -2-yl acid ) -prop-2-ynyl] -piperidm-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoiin-4-yl)propyl]-1 -[3-(oxazol-4-yl)-10 prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (oxazol-4-yl) - acid 10 prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(oxazol-5-yl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (oxazol-5-yl) - acid prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méÛioxyquinolin-4-yl)propyl]-l-[3-(pyridin-2-yl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique 15 Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yi)propyl]-l-[3-(pyridm-3-yl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methyloxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) - acid Prop-2-ynyl] -piperidin-3-yl} propan-1-oic acid (3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4) -yi) propyl] -l- [3- (pyridin-3-yl) -prop-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(R,S)-hydroxy-3-(6-méÛioxyquinolin-4-yl)propyl]- l-[3-(pyridin-4-yl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methyloxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl) - acid prop-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-(pyrimidm-2- 2 o yl)-prop-2-ynyl]-piperidm-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxy-iminolin-4-yl) propyl] -1 - [3- (pyrimidin-2-yl) -acid ) -prop-2-ynyl] -piperid-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R >S)-hydroxy-3-(6 •méthoxyquiüo3hi-4-yl)propyl]-l-[3-(pynmidin-4-y3)-proi>2-ynyI3-j)ipsridro-3-yl}prqiai-bi'îique(3R, 4R) -3- {4- [3- (R) S) -hydroxy-3- (6-methoxy-4-yl-4-yl) propyl] -1- [3- (pynmidin-4-yl) - proi> 2-ynyI3-j) ipsridro-3-yl} prqiai-bi'îique

Acide(3is^^)-3-{4-[3-(R,S)-h;/droxy-3-(6-mctbo;.yquii}olûi-/î-yl)î,jropylJ-l-[3-<pyïiimdin-5- γ1)-ρ'ορ-.?-γΐρΊ]-ρ;ρεπόΐη·3-γΙ}ρ··υρ3η-ί-οίφ!θ 25 Acide ('^V'R)-3-{4-[3-(R/S)bydroxy-3-(6-niéthûxyquiîJoIipJ-4-yl)propyl]-l-[3-(p),razin-2-yl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oiqueAcid (3is ^^) - 3- {4- [3- (R, S) -h; / droxy-3- (6-mctbo; .yquii olûi-} / î-yl) î, jropylJ-l- [ 3- <pyimimdin-5- γ1) -ρ'ορ-?-ΓΐρΊ] -ρ; ρεπόΐη · 3-γΙ} ρ ·· υρ3η-ί-οίφ! Θ 25 Acid ('^ V'R) -3- {4- [3- (R / S) bydroxy-3- (6-niéthûxyquiîJoIipJ-4-yl) propyl] -l- [3- (p), Razin-2-yl) -prop-2-ynyl] - piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridazin-3-yl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) - acid prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R3)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]- 1 -[3-(pyridazin-4- 3 0 yl)-prop-2-ynyl]-piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (R3) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4-yl)) - prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-métiioxyquinolin-4-yl)propyl]-l-[3-phénylpropyl]piperidin-3-yl}propan- 1-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methioxyquinolin-4-yl) propyl] -1- [3-phenylpropyl] piperidin-3-yl} acid 1-propane

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-phénylbutyl]piperidin-3-yl }propan-1 -oique 3 5 Acide (3R,4R)-3- {4-[3-(R-S)-{îuoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-fluorophényl)propyl]piperidin-3-yl}propan-1 -oique 120 2 2 130(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4-phenylbutyl] piperidin-3-yl} acid (3R, 4R) -3- {4- [3- (RS) - {1-fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2H) propan-1-ol -fluorophenyl) propyl] piperidin-3-yl} propan-1-oic 120 2 2 130

Acide (3R,4R>3-{4-[3-(R,S)-fluoro-3-(6-méthoxyquino]m-4-yl)iTOpyl]-l-[4-(2-fluorophényl)butyl]piperidin-3-yl}prqpan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquino) -m-4-yl) -N-pyl] -1- [4- (2-fluorophenyl) butyl] acid piperidin-3-yl} prqpan-l-oic acid

Acide (3R,4R)-3-{4-[3-(R,S>fiuoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-fluorophényl)prcç>yl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) propyl} acid] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(3-fluorophényl)butyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-fluorophenyl) butyl] piperidine -3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fiuoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-fluorophényI)propyl]piperidm-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) propyl] piperidm acid -3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(4-fluorophényl)butyl]piperidin-3-yl }propan-1-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-fluorophenyl) butyl] piperidine -3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]- l-[3-(2,3-difluoro-phényl)propyl]piperidin-3-yl}prqpan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl) ) propyl] piperidin-3-yl} prqpan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(2,3-difiuoro-phényl)butyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,3-difluoro-phenyl) acid ) butyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R.S)-fluoro-3-{6-méthGxyquinolin-4-yl)propyi]-l-[3-(2,6-difluoro-phényl)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (RS) -Fluoro-3- (6-methylquinolin-4-yl) propyl] -1- [3- (2,6-difluoro-phenyl) propyl) -acrylic acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(2,6-difluoro-phényl)butylJpiperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-difluorophenyl) -acid ) butylJpiperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-chloro-phényl)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-phenyl) propyl) -acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(2-chloro-phényl)butyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (2-chloro-phenyl) butyl] acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-chloro-phényl)propyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-phenyl) propyl) -acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(3-chloro-phényl)butyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-chloro-phenyl) butyl] acid ] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-mé±oxyquinolin-4-yI)propyl]-l -[3-(4-chloro-phényl)propyl]piperidin-3 -yl } propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxy-quinolin-4-yl) propyl] -1 - [3- (4-chlorophenyl) -acidic acid ) propyl] piperidin-3-yl} propan-1-oic

Acide (3R.4R)-3- {4-[3-(R.S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(4-chloro-phényl)butyl]piperidin-3-yl}propan-1 -oique(3R4R) -3- {4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-chlorophenyl) butyl] piperidine acid -3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,3-dichloro-phényl)propyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (2,3-dichlorophenyl) -acid ) propyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[4-(2,3-dichioro-phényl)butyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [4- (2,3-dichloro-phenyl) ) butyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,6-dichloro- phényl)propyl]piperidin-3-yl }propan-1 -oique 120 22 131(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-dichlorophenyl) acid ) propyl] piperidin-3-yl} propan-1-oic 120 22 131

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(2,6-dichloro-phényl)butyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [4- (2,6-dichlorophenyl) -acid ) butyl] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(2-mélhyl-phényl)propyl]piperidin-3-yl}propan-l-oique 5 Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyi]- l-[4-(2-méthyl-phényl)butyl]piperidin-3-yi}propan-l -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxy-iminolin-4-yl) propyl] -1- [3- (2-methylphenyl) propyl] -acrylic acid ] (3 R, 4 R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -acrylic acid 1- [4- (2-methyl-phenyl) butyl] piperidin-3-yl} propan-1-ol

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[5-(2-métbyl-phényl)pentyljpiperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [5- (2-methylbenzyl) pentyl] piperidinic acid -3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyqumo]in-4-yl)propyl]-1 -[3-(3-méthyl-10 phényl)propyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyqumo) -in-4-yl) propyl] -1- [3- (3-methyl-10) -acid phenyl) propyl] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyI]- l-[4-(3-métb.yl-phényl)butyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxy-iminolin-4-yl) propyl] -1- [4- (3-methyl) -phenyl] -acrylate ) butyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-méthyl-phényl)propyl]piperidin-3-yl}propan-l-oique 15 Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-l-[4-(4-méthyl-phényl)butyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methyl-phenyl) propyl] -acid ] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquolin-4-yl) propyl] -acetate] 1- [4- (4-methyl-phenyl) butyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-{luoro-3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(2-méthoxy-phényl)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) - {luoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenyl)) acid propyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4~(2-méthoxy- 2 o phényl)butyl]piperidin-3-yl}prppan-l-oique(3R, 4R) -3- {4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [4 - [(2-methoxy-2-phenyl) butyl] acid ] piperidin-3-yl} prppan-l-oic acid

Acide (3R,4R)-3-{4-[3-(R^S)-ffuoro-3-(6-nîéibo^qiûiiOiirr4-y])propyl]-]-[3-(3-méittoxy-phény])prûpyi]piperidin-3-yl}propa<i-l-oique(3R, 4R) -3- {4- [3- (R3 S) -affluoro-3- (6-nitroquinyl) -2-yl] propyl] -] - [3- (3-methoxyphenyl)] ) prûpyi] piperidin-3-yl} propa <il-oic

Acide (3R/:R)-3-{4-[3-(R.S)~i! 'oro-3- (6-roéîbo wqu’noîin- l-yOpropyl]-1 -[4-(3-méüioxy-j)iién_yl)U}ty]]i.àpCijdjii -3-yl}p, vpau-i -oique 25 Acide (3R/-tR)-3-{4-[3-( *,S)-iixiorü-3-(6~méthoxyquiiionn-4-yl)propyl]-l-[3-(4-méthoxy-phéuyî)propyl]piperidin-3 -yl }propan-1 -oiqueAcid (3R /: R) -3- {4- [3- (R.S) ~ i! oro-3- (6-fluoroquinyl-1-ylpropyl] -1- [4- (3-methyloxy) phenyl) propyl] -1-yl] -3-yl} p, vpau-i (3R-) -3- {4- [3- (*, S) -Iixioryl-3- (6-methoxyquin-4-yl) propyl] -1- [3- (4-methoxy) -acetic acid propylene] propyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-xnéthoxyquinolin-4-yl)propyl]-l -[4-(4-méthoxy-phényl)butyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-xethoxyquinolin-4-yl) propyl] -1- [4- (4-methoxy-phenyl) butyl] acid ] piperidin-3-yl} propan-1-oic

Acide (3R4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinoîin-4-yl)propyl]-1 -[3-(2-trifluoro- 3 o méthylphényl)propyl]piperidin-3-yl}propan-1 -oique(3R4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinin-4-yl) propyl] -1- [3- (2-trifluoromethylphenyl) propyl] -acrylic acid; ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fiuoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[4-(2-trifluoro-méthylphényl)butyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [4- (2-trifluoromethylphenyl) butyl] acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]- l-[3-(3-trifluoro-méthylphényl)propyl]piperidin-3-yl}propan-1 -oique 3 5 Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(3-trifluoro-méthylphényl)butyl]pipendm-3-yl}propan-l-oique 120 2 2 132(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenyl) propyl] -acrylic acid ] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] 3-piperidin-3-yl} propan-1-ol -1- [4- (3-trifluoromethylphenyl) butyl] pipendm-3-yl} propan-1-ol 120 2 2 132

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin^4-yl)propyl]-1 -[3-(4-trifluoro-méthylphényl)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenyl) propyl) -acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(4-ttifluoro-méthylphényl)butyl]piperidin-3-yl}propan-1 -oique 5 Acide (3R,4R)-3- {4-[3-(R,S>fluoro-3-{6-méthoxyquinolin-4-yl)propyl]-1 -[2-phénylthio-éthyl]piperidin-3-yl}propan- 1-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (4-tifluoromethylphenyl) butyl] acid ] (3 R, 4 R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 -acid-1-yl} propan-1-acid - [2-phenylthioethyl] piperidin-3-yl} propan-1-ol

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propylJ-l-[3-phénylthio-propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylthiopropyl] piperidin-3-yl acid } propan-1 -oic

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-niéthoxyquinolin-4-yl)propyl]-l -[2-(2-fluoro-10 phénylthio)éthyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-fluoro-phenylthio) acid) ethyl] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-fluoro-phénylthio)propyl]piperidm-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluoro-phenylthio) propyl) -acid ] piperidm-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3-fluoro-phénylthio)éthyl]piperidin-3-yl}propan-l-oique 15 Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-fluoro- phénylthio)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluoro-phenylthio) ethyl acid ] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -acryl-1-yl} propan-1-ol 1- [3- (3-fluorophenylthio) propyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[2-(4-fluoro-phénylthio)éthyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [2- (4-fluoro-phenylthio) ethyl acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-inéthoxyquinolin-4-yl)propyl]-1 -[3-(4-fluoro-2 o phénylthio)propyl]piperidm-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (4-fluoro-2-phenylthio) -acid ) propyl] piperidm-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2,3-difluoro-phénylthio)éthyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-difluoro-phenylthio) ethyl acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,3-difluoro-phénylthio)propyl]piperidin-3-yl}propan-1 -oique 2 5 Acide (3R,4R)-3- {4-[3-(R,S)-iluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2,6-difluoro- phénylthio)éthyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluoro-phenylthio) -acidic acid ) propyl] piperidin-3-yl} propan-1-oic acid (3R, 4R) -3- {4- [3- (R, S) -iluoro-3- (6-methoxyquinolin-4-yl)} propyl] -1- [2- (2,6-difluorophenylthio) ethyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,6-difluoro-phénylthio)propyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluoro-phenylthio) -acidic acid ) propyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2-chloro- 3 o phénylthio)éthyl]piperidin-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (2-chlorophenylthio) -acid ) ethyl] piperidin-3-yl} propan-1-ol

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-chloro-phénylthio)propy]]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-phenylthio) propyl) ]] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3-chloro-phénylthio)éthyl]piperidin-3-yi }propan-1 -oique 3 5 Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-chloro- phénylthio)propyl]piperidin-3-yl }propan-1 -oique 120 2 2 133(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chloro-phenylthio) ethyl acid ] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] 3-piperidin-3-yl} propan-1-ol -1- [3- (3-chlorophenylthio) propyl] piperidin-3-yl} propan-1-oic 120 2 133

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(4-chloro- phénylthio)éthyl3piperidin-3-yi}propaQ-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (4-chlorophenylthio) ethyl) piperidinic acid -3-yi} propaQ-1 -oic

Acide (3R,4R)-3-{4-[3-{R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(4-chIoro- phénylthio)propyl]piperidm-3-yl}propan- 1-oique 5 Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin4-yl)propyI]-l-[2-(2,3-dichloro-phénylthio)éthyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenylthio) propyl) ] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -acrylic acid] [2- (2,3-dichloro-phenylthio) ethyl] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,3-dichloro-phényltHo)propyl]piperidin-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-dichlorophenyl) HCl acid ) propyl] piperidin-3-yl} propan-1-ol

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-l-[2-(2!6-dichloro-10 phénylthio)éthyl]piperidm-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxy-iminolin-4-yl) -propyl] -1- [2- (2-dichloro) -10-dichloroacetic acid; phenylthio) ethyl] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 ~[3-(2,6-dichloro-phénylthio)propyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-dichlorophenylthio) ) propyl] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(KS)-fluoro-3-(6-méthoxyquinolm^yl)propyl]-l-[2-(2-méthyl-phénylthio)éthyl]piperidin-3-yl}propan- 1-oique 15 Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-méthyi- phénylthio)propyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (KS) -fluoro-3- (6-methoxyquinol-1-yl) propyl] -1- [2- (2-methyl-phenylthio) ethyl] piperidin-3-acid (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-yl] propan-1-yl - (2-Methylphenylthio) propyl] piperidin-3-yl} propan-1-ol

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(3-méthyl-phénylthio)éthyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methyl-phenylthio) ethyl acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(RS)-fluoro-3-(6-rnéthoxyqumolin-4-yl)propyl]- l-[3-{3-méthyl-2 0 phénylthio)propyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (RS) -Fluoro-3- (6-methoxy-iminolin-4-yl) propyl] -1- [3- (3-methyl-2-phenylthio) propyl) -acid ] piperidin-3-yl} propan-1-oic

Acide (3R,dR)-3-{4-f3-(R,S)-fluoro-3-(6-méthoxyquinobn-4-yî)propyl]-l-[2-(4-méthyl-phénykhio)éthyl]piperidin-3 yl} propan-1 -oique(3R, dR) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinob-4-yl) propyl] -1- [2- (4-methyl-phenyl) ethyl] -acid] piperidin-3-yl} propan-1-oic

Acide (3RJ4R)-3-{4-[3-(R,S)-iluûro-3-(6-inéthoxyquinolin-4-yl)propyl]-l-[3-(4-méthyl-phény)tbio)propyl]pipendin-3-yl}propan-}-oique 2 5 Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-méthoxyquinobn-4-yl)propyl]-l-[2-(2-trifluoro- méîliylhénylthio)éthyl]piperidin-3 -yl} propan-1 -oique(3RJ4R) -3- {4- [3- (R, S) -Illuuro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenyl) tbio) propyl acid ] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinobn-4-yl) propyl] -2-propan-3-yl} propanic acid 1- [2- (2-Trifluoromethylphenylthio) ethyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(RS)-fluoro-3-(6-méthoxyquinobn-4-yl)propyl]-1 -[3-(2-trifluro-méthylphénylthio)propyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (RS) -Fluoro-3- (6-methoxyquinob-4-yl) propyl] -1- [3- (2-trifluoromethylphenylthio) propyl] piperidine -3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3-trifluoro- 3 0 méthylhénylthio)éthyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethylphenylthio) ethyl acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-trifluro-méthylphénylthio)propyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenylthio) propyl] piperidinic acid -3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(4-trifluoro-méthylhénylthio)éthyl]piperidin-3-yl}propan-1 -oique 3 5 Acide (3R,4R)-3-{4-[3-(R,S)-fiuoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(4-trifluro-méthylphénylthio)propyl]piperidin-3-yl}propan-1 -oique 120 2 2 134(3R, 4R) -3- {4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-trifluoromethyl-phenylthio) ethyl] piperidinic acid -3-yl} propan-1-oic acid (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -l - [3- (4-trifluoromethylphenylthio) propyl] piperidin-3-yl} propan-1-oic 120 2 2 134

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2-méthoxy-phénylthio)éthyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methoxy-phenylthio) ethyl acid ] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[3-(2-méihoxy-phénylthio)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinin-4-yl) propyl] -1- [3- (2-methoxyphenylthio) propyl) ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-{6-méthoxyquinolm-4-yl)propyl]-1 -[2-(3-méthoxy-phénylthio)éthyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [2- (3-methoxy-phenylthio) ethyl acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthoxy-phénylthio)propyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxy-phenylthio) propyl) -acid ] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[2-(4-méthoxy-phénylthio)éthyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methoxy-phenylthio) ethyl acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(4-méthoxy-phénylthio)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (4-methoxyphenylthio) propyl) -acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[cyclopropyl-méthyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [cyclopropyl-methyl] piperidin-3-yl} propanic acid 1 -Oic

Acide (3R,4R)-3- {4-[3-(R.S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[2-(cyclopropyl)éthyl]piperidin-3 -y]} propan-1 -oique(3R, 4R) -3- {4- [3- (RS) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1 - [2- (cyclopropyl) ethyl] piperidin-3-y acid ]} propan-1 -oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinoliii-4-yl)propyl]-1 -[cyclobutyl-méthyl]piperidin-3-yl} propan-1-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [cyclobutylmethyl] piperidin-3-yl} propan-1-oic acid

Acide (3R,4R)-3- {4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(cyclobutyl)éthyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (cyclobutyl) ethyl] piperidin-3-yl acid } propane-l-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-mélhoxyquinolin^-yl)propyl]-1 -[cyclopentyl-méthyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-melhoxyquinolin-1-yl) propyl] -1 - [cyclopentyl-methyl] piperidin-3-yl} propanic acid -1 -oic

Acide (3R,4R)-3- {4-[3-(RS)-fluoro-3-(6-métboxyquinolin-4-yl)propyi]-1 -[2-(cyclopentyl)é±yl]piperidin-3 -yl} propan-1 -oique(3R, 4R) -3- {4- [3- (RS) -Fluoro-3- (6-metboxyquinolin-4-yl) propyl] -1- [2- (cyclopentyl) γ-yl] piperidin-3-acid -yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(RS)-fluoro-3-(6-méthoxyquinolin^-yl)propyl]-1 -[cyclohexyl-méthyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-1-yl) propyl] -1 - [cyclohexylmethyl] piperidin-3-yl} propan-1 acid -oique

Acide (3R,4R)-3- {4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(cyclohexyl)éthyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidin-3-yl acid } propan-1 -oic

Acide (3R,4R)-3- {4-[3-{R.S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(cyclopropyl-thio)éthyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopropyl-thio) ethyl] piperidin-3-acid -yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(cyclopropyl-thio)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopropylthio) propyl] piperidin-3-acid -yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(cyclobutyl- thio)éthyl]piperidin-3-vl}propan-l-oique ’(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclobutylthio) ethyl] piperidinic acid -3-vl} propan-l-oic

Acide (3R,4R)-3- {4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-:l-yl)propyl]-1 -[3-(cyclobutyl- thiopropyl]piperidin-3-yl } propan-1 -oique 120 2 2 135(3R, 4R) -3- {4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-1-yl) propyl] -1 - [3- (cyclobutylthiopropyl) piperidin-3- acid yl} propan-1 -oic 120 2 2 135

Acide (3R,4R)-3-{4-[3-(R,S)-iluoro-3-(6-méthoxyquinolm-4-yl)propyl]-l-[2-(cyclopentyl-thio)éthyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Lluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidinic acid -3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinoim-4-yl)propyl]-1 -[3-(cyclopentyl-thio)propyl]piperidin-3-yl}propan-l-oique 5 Acide (3R,4R)-3- {4-[3-(R)S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]- l-[2-(cyclohexyl- thio)éthyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinoim-4-yl) propyl] -1- [3- (cyclopentylthio) propyl] piperidine acid -3-yl} propan-1-oic acid (3R, 4R) -3- {4- [3- (R) S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoK>-3-(6-méthoxyquinoIin-4-yl)propyl]- l-[3-(cyclohexyl-1hio)propyl]piperidin-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro] -3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclohexyl-1H) propyl] acid piperidin-3-yl} propan-l-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-mélhoxyquinolin-4-yl)propyl]-1 -[2-méthylthio-io éthyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-melhoxyquinolin-4-yl) propyl] -1- [2-methylthio-10-ethyl] piperidin-3-acid yl} propan-l-oic

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-méihoxyqumo]in-4-yl)propyl]-l-[3-méthylÜiio-propyl]piperidm-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methyloxy) -benzyl-4-yl) -propyl] -1- [3-methyl-i-propyl] piperidin acid; 3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-éthylthioéthyl]piperidin-3-yl}propan-1-oique 15 Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-éthylthiopropyl] piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-ethylthioethyl] piperidin-3-yl} acid propan-1-oic acid (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-ethylthiopropyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R.S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(n-propylthio)éthyl]piperidin-3-yl]propan-1 -oique(3R, 4R) -3- {4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (n-propylthio) ethyl] piperidin-3-acid -yl] propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-inéthoxyquinolin-4-yl)propyl]-l-[3-(n-propylthio)20 propyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (n-propylthio) propyl] acid piperidin-3-yl} propan-l-oic acid

Acide (3R^4R)-3-{4-[3-(R3)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(ii-butylthio)éthyl jpj J ;eridin-3-yl}propan-1 -oique(3 R, 4 R) -3- {4- [3- (R3) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (ii-butylthio) ethyl], eridin acid; -3-yl} propan-1-oic

Acide (3Ps4R)-3-{4-[3-(î<,S)-iluoro-3-(6-raétho?ryqi/iuolin-4~yl)propyl]-l-[3-(n-butylthio)propyUpiperidin-3-yl}propan-l-oique 2 5 Acide (3R,4R.)-3-{4[3-(R,S)-iluoro-3-(6-méihoxytpjmolin-4-yl)propyl]-l-[3-(thien-2-yl) propyl]piperidin-3-yl}propan-1 -oique(3Ps4R) -3- {4- [3- (1 H, S) -Lluoro-3- (6-ethethoxy) -iminolin-4-yl) propyl] -1- [3- (n-butylthio) acid) propy-1-pyridin-3-yl} propan-1-oic acid (3R, 4R.) - 3- {4- [3- (R, S) -Iluoro-3- (6-methyloxy) p -molin-4-yl) propyl] - 1- [3- (thien-2-yl) propyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(thien-2-yl)butyl]piperidin-3-yI }propan-l -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-2-yl) butyl] acid ] piperidin-3-yl} propan-l-oic

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(thien-2-yl) 30 thioéthyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl)) acid thioethyl] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- [4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 ~[3-(thien-2-yl)thiopropyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- [4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) thiopropyl) acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-iluoro-3-(6-méthoxyquinolin^-yl)propy]]-1 -[3-(5-chloro-thien2-yl)propyi]piperidin-3-yl}propan-1 -oique 3 5 Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(5-chIoro-thien 2-yl)butyl]piperidin-3-yl}propan-1 -oique 12 0 2 2 136(3R, 4R) -3- {4- [3- (R, S) -Lluoro-3- (6-methoxyquinolin-1-yl) propyl]] - 1 - [3- (5-chloro-thien-2-yl) acid Propyl (piperidin-3-yl) propan-1-oic acid (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl)) propyl] -1- [4- (5-chloro-thien-2-yl) butyl] piperidin-3-yl} propan-1-oic 12 0 2 2 136

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(5-chloro-thien-2-yl)thioéthyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (5-chloro-thien-2) -acidic acid -yl) thioethyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[3-(5-chloro-thien-2-yl)thiopropyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinin-4-yl) propyl] -1 - [3- (5-chloro-thien-2) -acid -yl) thiopropyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)prqpyl]-1 -[3-(3-chloro-tbien-2-yl)propyl]piperidm-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-chloro-tert-2-ene) acid -yl) propyl] piperidm-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(3-chloro-thien-2-yI)butyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [4- (3-chloro-thien-2-yl) acid ) butyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méîhoxyquinolin^-yl)propyl]-1 -[2-(3-chloro-thien-2-yl)tbioéthyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-1-yl) propyl] -1 - [2- (3-chloro-thien-2-) -acidic acid yl) tbioethyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-chloro-thien-2-yl)thiopropyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-chloro-thien-2-yl) -acidic acid -yl) thiopropyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(5-mé±yl -thien-2-yl)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-methyl-thien) -acid -2-yl) propyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(5-méthyl -thien-2-yl)butyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [4- (5-methylthien-2) -acid -yl) butyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(5-méthyl -tbien-2-yl)thioétbyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (5-methyl-2-benzene) -yl) thioetbyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R.S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(5-méthyl -thien-2-yl)thiopropyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (5-methyl-thien-2-yl) -acid thiopropyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-méthyl -thien-2-yl)propyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-thien-2-yl) -acid ) propyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-iluoro-3-(6-méthoxyquinolin^-yl)propyl]-1 -[4-(3-méthyl -thien-2-yl)butyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Iluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (3-methylthien-2-yl) -acetyl-3- yl) butyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3-méthyl -thien-2-yl)thioéthyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (3-methylthien-2) -acid -yl) thioethyl] piperidin-3-yl} propan-1-oic

Acide (3R.4R)-3-{4-[3-(R.S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l -[3-(3-méthyl -thien-2-yl)thiopropyl]piperidin-3-yl }propan-1 -oique(3R4R) -3- {4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-methyl-thien-2-yl) -acid thiopropyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thien-3-yl)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) propyl) -acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(thien-3-yl)butyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-3-yl) butyl] acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(thien-3-yl) thioéthyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (thien-3-yl) thioethyl acid ] piperidin-3-yl} propan-1-oic

Acide (3R.4R)-3- {4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(thien-3-yl) ±iopropyl]piperidin-3-yl}propan-1 -oique 120 2 2 137(3R4R) -3- {4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) ± iopropyl] acid piperidin-3-yl} propan-1-oic 120 2 2 137

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-niéthoxyquinolin-4-yl)propyl]-1 -[3-(fur-2-yl)propyl]piperidin-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fur-2-yl) propyl) -acid ] piperidin-3-yl} propan-l-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-métboxyquinolin-4-yl)propyl]-1 -[4-(fur-2-yl)butyl]piperidin-3-yl}propan-l -oique 5 Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[2-(fur-2-yl) thioéthyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-metboxyquinolin-4-yl) propyl] -1- [4- (fur-2-yl) butyl] acid ] (3 R, 4 R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxy-iminolin-4-yl) -propyl] propan-1-ol 1- [2- (Fur-2-yl) thioethyl] piperidin-3-yl} propan-1-ol

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(fur-2-yl)thiopropyl]piperidin-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (fur-2-yl) thiopropyl acid ] piperidin-3-yl} propan-l-oic

Acide (3R,4R)-3-{4-[3-(R,S)-iluoro-3-(6-méthoxyqumolm-4-yl)propyl]-l-[3-(fur-3-yI) 1 ό propyl]piperidin-3-yl}prqpan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Lluoro-3- (6-methoxyqumol-4-yl) propyl] -1- [3- (fur-3-yl) 1 ό propyl] piperidin-3-yl} prqpan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-iluoro-3-(6-méthoxyquinoiin-4-yl)propyl]-1 -[4-(fur-3-yl)butyl]piperidin-3-yl}propan- 1-oique(3R, 4R) -3- {4- [3- (R, S) -Iluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (fur-3-yl) butyl] acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-iluoro-3-(6-méthoxyqumoiiii-4-yl)propyl]- l-[2-(ftir-3-yl)thioéthyl]piperidin-3-yl}propan- 1-oique 15 Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyqiunolin-4-yl)propyl]-1 -[3-(fur-3-yl) thiopropyl]piperidm-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Iluoro-3- (6-methoxy-4-yl) propyl] -1- [2- (tert-3-yl) thioethyl acid ] (3 R, 4 R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -acetate 1 - [3- (fur-3-yl) thiopropyl] piperid-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-niéthoxyquinolin-4-yl)propyl]-1 -[3-( 1 -méthyl-pynol-2-yl)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (1-methyl-pynol-2) -acid -yl) propyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-méihoxyquinolin-4-yl)propyl]-l-[4-(l-inéthyl- 2 0 pyrrol-2-yl)butyl]piperidm-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1-methylpyrrol) acid -2-yl) butyl] piperidm-3-yl} propan-1-ol

Acide (3R,4R)-3-{4-[3-(R,S}-fluoro-3-(6-méthox5rfpiinolin-4-yl)propyl]-l-[2-(l-méthyl-pynol-2-yi)tluc>éihyl]pipsridîn--3-yl}p;opan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxymirolin-4-yl) propyl] -1- [2- (1-methyl-pynol-2) -acid -yi) tluc> eihyl] pipsridin-3-yl} p; opan-1-oic

Acide (3R,4R)-3-{4-[3-(R}S)-fluoîO-3-(6-nîéfboj:yqi»noîin-4-yl)propyl]-l-[3-(l-médiyl-p)'nOl-2-yl)Îh.iopropyI]pii>ciidiH-3-yi}prop:îii-1 -oique 25 Acide (3R,4R)-3-{4-[3-(I^S}-i'uoîO-3-(6-méÎboxyquinoliii-4-yl)propyl]-l-[3-(l-méÎhyl-pyrrol-2-yl)propyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R) S) -Fluoro-3- (6-naphthyl) -benzoyl-4-yl) propyl] -1- [3- (1-methyl) acid ## STR2 ## Acid (3R, 4R) -3- {4- [3- (I) S) -N-1-yl-1-yl) pyridinyl-3-yl} propan-1-yl -i'uoîO-3- (6-méÎboxyquinoliii-4-yl) propyl] -l- [3- (l-méÎhyl-pyrrol-2-yl) propyl] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(l-méthyl-pyrrol-3-yl)butyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [4- (1-methyl-pyrrol-3) -acid -yl) butyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[2-( 1 -méthyl- 3 o pyrrol-3-yl)thioéthyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1 - [2- (1-methyl-3-pyrrole) acid 3-yl) thioethyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(l-méthyl-pyrrol-3-yl)thiopropyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methyl-pyrrol-3) -acid yl) thiopropyl] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(thiazol-2-yl) propyl]piperidin-3-yl}propan-1 -oique 3 5 Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm4-yl)propvi]-1 -[4-(thiazol-2-yl) butyl]piperidin-3 -yl }propan-1 -oique il 2 0 2 2 138(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazol-2-yl) propyl) -acid ] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinol-4-yl) propyl] -1 -acid-3-yl} propan-1-acid - [4- (thiazol-2-yl) butyl] piperidin-3-yl} propan-1-oic il 2 0 2 2 138

Acide (3R4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(thiazol-2-yl)thioéthyl]piperidin-3-yl }propan- 1-oique(3R4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thiazol-2-yl) thioethyl] piperidinic acid -3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(thiazol-2-yl)thiopropyl]piperidin-3-yl}prcpan-1 -oique(3R, 4R) -3- {4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazol-2-yl) thiopropyl] piperidinic acid -3-yl} prcpan-1 -oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluorO-3-(6-méihoxyquinolin-4-yl)propyl]-1 -[3-( 1 -méthyl-imidazol-2-yl)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (1-methyl-imidazol-2) -acidazol -yl) propyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[4-(l -méthyl-imidazol-2-yl)butyl]piperidm-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (1-methylimidazole) -acidazol -2-yl) butyl] piperidm-3-yl} propan-1-oic

Acide (3R4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-( 1 -méthyl-imidazol-2-yl)thioéthyl]piperidin-3-yl}propan-1 -oique(3R4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (1-methyl-imidazol-2-yl) -acid ) thioethyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-1-(3-(1 -méthyl-imidazol-2-yl)thiopropyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxy-iminolin-4-yl) propyl] -1- (3- (1-methyl-imidazol-2) -acidazol -yl) thiopropyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl-imidazol-4-yl)propyl]piperidm-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-methyl-imidazol-4) -acidazol yl) propyl] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(3-méthyl-imidazol-4-yl)butyl]piperidin-3 -yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [4- (3-methyl-imidazol) -4-acid -yl) butyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3-rnéthyl-imida2ol-4-yl)thioéthyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (3-methyl-imidazol-4-yl) ) thioethyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fiuoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl-imidazol-4-yl)Üiiopropyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-methyl-imidazol-4) -acidazol -yl) ioiopropyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl-pyrazol-4-yl)propyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-methyl-pyrazol-4) -acid -yl) propyl] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm^l-yl)propyl]-1 -[4-(3-méthyl-pyrazol-4~yl)butyl]piperidm-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-1-yl) propyl] -1 - [4- (3-methyl-pyrazol-4) -acid ~ yl) butyl] piperidm-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3-méthyl-pyrazol-4-yl)thioéthyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (3-methyl-pyrazol-4) -acid -yl) thioethyl] piperidin-3-yl} propan-1-oic

Acide (3R4R)-3- {4-[3-(RS)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-(3-méthyl-pyrazol-4-yl)thiopropyl]piperidin-3-yl}propan-1 -oique(3R4R) -3- {4- [3- (RS) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (3-methyl-pyrazol-4-yl) thiopropyl acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(oxazol-2-yl)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (oxazol-2-yl) propyl) -acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l -[4-(oxazol-2-yl)butyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (oxazol-2-yl) butyl] piperidine -3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(oxazol-2-yl)thioéîhyl]piperidin-3-vl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (oxazol-2-yl) thioheyl) acid ] piperidin-3-vl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(oxazol-2-yl)thiopropyl]piperidin-3-yl} propan-1 -oique 120 2 2 320 2 2 139(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) thiopropyl) acid ] piperidin-3-yl} propan-1-oic 120 2 2 320 2 2 139

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridin-2-yl)propyl]piperidin-3-yl}propan-l oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) propyl) -acid ] piperidin-3-yl} propan-l oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-niéthoxyquinolin-4-yl)propyl]-1 -[4-(pyridin-2-yl)butyl]piperidm-3-yl}propan-l-oique 5 Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyridin-2-yl)ihioéthyl]piperidin-3-yl}propan-loique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridin-2-yl) butyl] acid ] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -acetate] 1- [2- (Pyridin-2-yl) 1Hioethyl] piperidin-3-yl} propan-1-ol

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridin-2-yl)thiopropyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (pyridin-2-yl) thiopropyl acid ] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l -[3-(pyridin-3-yl) 10 propyl]piperidin-3-yl}propan-l oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (pyridin-3-yl) acid propyl] piperidin-3-yl} propan-l oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-niéthoxyquinolin-4-y])propyl]-1 -[4-(pyridin-3-yl)butyl]piperidin-3-yl}propan-1 oique(3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [4- (pyridin-3-yl) acid butyl] piperidin-3-yl} propan-1ic

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(pyridm-3-yl)thioéthyl]piperidin-3-yl}propan-1 oique 15 Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méÎhoxyquinolin-4-y])propyl]-1 -[3-(pyridin-3-yl) thiopropyl]piperidin-3-yl}propan-l oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-3-yl) thioethyl acid ] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -acetate] 1- [3- (pyridin-3-yl) thiopropyl] piperidin-3-yl} propan-1-ol

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[3-(pyridin-4-yl)propyl]piperidin-3-yl}propan-1 oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinin-4-yl) propyl] -1- [3- (pyridin-4-yl) propyl) -acid ] piperidin-3-yl} propan-1ic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[4-(pyridin-4-yl) 20 butyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1 - [4- (pyridin-4-yl) -acid butyl] piperidin-3-yl} propan-l-oic acid

Acide (3R>4R)-3-{4-[3-0^3S)-flnoro-3-(6'înétho>p,quînoliu-4-yI)piOpyI]-l-[5-(pyiidin-4-yl)pf-· ityljpipenditt -S-y^propan-1 -oique(3R- (4R) -3- {4- [3-O 3 S) -flnoro-3- (6'-n-thio-p, quinolin-4-yl) piO-pI] -1- [5- (pyidin-4-yl) acid yl) pf- · ityljpipenditt -Sy ^ propan-1 -oic

Aride (3R,4R)-3- rjion>3-(6-iir;dx»<yqwiioli;’-4-yl^)roî>yi3-l-[2“(pyridin-4-yl) îbioôftiyl]'pip:'rjdiii--3-yI}p!Op :u-loi-.jue 25 Acide (3R,4R)-3-{4-f3{R,S)-iluoro-3-(6-niô;bo;çyquinoiin-4-yl)propyî]-l-[3-(pyiidin-4-yI)thiopropyl]pipeïidin-3~yl}propan-1 oiqueAride (3R, 4R) -3- [3- (6-yl) -2- (4-yl) -2-yl] -1- [2 - (pyridin-4-yl) benzothiazol) pip ## STR3 ## Acid (3R, 4R) -3- {4- (R, S) -iluoro-3- (6-chloro); γ-quinolin-4-yl) propyl] -1- [3- (pyidin-4-yl) thiopropyl] pipidin-3-yl} propan-1-ol

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-2-yl)propyl]piperidin-3-yl} propan-1 oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) propyl) -acid ] piperidin-3-yl} propan-1ic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l -[4-(pyrimidin-2-yl)30 butyl]piperidin-3-yl}propan-loique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [4- (pyrimidin-2-yl) acid butyl] piperidin-3-yl} propan-loique

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin4-yl)propyl]-1 -[2-(pyrimidin-2-yl)thioéthyl]piperidin-3-yl }propan-1 oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (pyrimidin-2-yl) thioethyl] piperidine acid -3-yl} propan-1ic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-2-yl)thiopropyl]piperidin-3 -yl} propan-1 oique 3 5 Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-4-yl) propyl]piperidin-3-yl }propan-1 oique <12 0 2 2 140(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) thiopropyl acid ] (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -acetate (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] 1- [3- (pyrimidin-4-yl) propyl] piperidin-3-yl} propan-1ic acid <12 0 2 2 140

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[4-(pyrimidin-4-yl)butyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinin-4-yl) propyl] -1 - [4- (pyrimidin-4-yl) butyl] acid ] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyrimidin-4-yl)tfroéthyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (pyrimidin-4-yl) -frethyl-acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-méthoxyquinoIin-4-yl)propyl]-l-[3-(pyrimidin-4-yl)tbiopropyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinin-4-yl) propyl] -1- [3- (pyrimidin-4-yl) tbiopropyl acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-5-yl)propyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-5-yl) propyl) -acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(pyrimidin-5-yl)butyl]piperidin-3-yl}propan-1-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrimidin-5-yl) butyl} acid ] piperidin-3-yl} propan-1-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyrimidin-5-yl)thioéthyl]piperidin-3 -yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (pyrimidin-5-yl) thioethyl acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-fiuoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(pyriinidin-5-yl)thioprqpyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyriinidin-5-yl) thioprophyl acid ] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(pyrazin-2-yl)propyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) propyl acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(pyrazin-2-yl)butyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrazin-2-yl) butyl] acid ] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin^-yl)propyl]-1 -[2-(pyrazin-2-yl)thioéthyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-2-yl) propyl] -1- [2- (pyrazin-2-yl) thioethyl] acid piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(pyrazm-2-yl)thiopropyl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (pyrazol-2-yl) thiopropyl acid ] piperidin-3-yl} propan-1-oic

Acide (3R_4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridazin-3-yl)propyl]piperidin-3-yl} propan-1 -oique(3R_4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) propyl] piperidine acid -3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(pyridazin-3-yl)butyl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridazin-3-yl) butyl] acid ] piperidin-3-yl} propan-1-oic

Acide (3R-4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyridazin-3-yl)thioéthyI]piperidin-3-vl}propan-1 -oique(3R-4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (pyridazin-3-yl) thioethyl] acid ] piperidin-3-vl} propan-1-oic

Acide ( 3R.4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridazin-3-yl)tbiopropyl]piperidin-3-yl} propan-1 -oique(3R4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) tbiopropyl acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridazin-4-yl)propyl]piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4-yl) propyl) -acid ] piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-(pyridazin-4-yl)butyl]piperidin-3-vl}propan-l-oique ·(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4- (pyridazin-4-yl) butyl} acid ] piperidin-3-vl} propan-l-oic ·

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyridazin-4-yl)thioéthyl]piperidin-3-yl}propan-l-oique x ΓΙ2ο ? ? 141(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (pyridazin-4-yl) thioethyl acid ] piperidin-3-yl} propan-l-oic x ΓΙ2ο? ? 141

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridazin-4-yl)thiopropyl]piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4-yl) thiopropyl acid ] piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-médioxyquinolin-4-yl)propyl]- l-[3-phényl-prop-2-ynyl]-piperidm-3-yl}propan-l-oique 5 Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-inélhoxyquinolin-4-yl)propyl]-l-[3-(2-fluoro-phényiyprop-2-ynyl]-piperidm-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-medioxyquinolin-4-yl) propyl] -1- [3-phenyl-prop-2-ynyl] acid -piperidm-3-yl} propan-1-oic acid (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-inelhoxyquinolin-4-yl) propyl] - l- [3- (2-fluoro-phényiyprop-2-ynyl] -piperidm-3-yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-méÜioxyquinolin-4-yl)propyl]-l-[3-(3-fluoro-phényl)-prop-2-ynyl3-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methyloxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-phenyl) - acid prop-2-ynyl3-piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-{R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-fluoro-io phényl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluoro-phenyl) acid) -prop-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-iluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-chloro-phényl)-prüp-2-ynylj-piperidio-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Lluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (2-chlorophenyl) - acid PRUP-2-ynylj-piperidio-3-yl} propan-l-oic acid

Acide (3RylR)-3-{4-[3-(R,S>fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-cHoro-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique 15 Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyqumoim-4-yl)propyl]-l -[3-(4-chloro- phényl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3RylR) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-phenyl) -prop-2) -acid -ynyl] -piperidin-3-yl} propan-1-oic acid (3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquimmon-4-yl)} propyl] -1- [3- (4-chlorophenyl) prop-2-ynyl] piperidin-3-yl} propan-1-ol

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-niéthoxyquinoliii-4-yl)propyl]-l-[3-(2-méthyl-phényl)-prop-2-ynyl]-piperidin-3--yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenyl)) - prop-2-ynyl] -piperidin-3 - yl} propan-l-oic acid

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-méîhoxyquinolin-4-yl)propyl]-l-[3-(3-méthyl-2 0 phényl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl) phenyl) -acid ) -prop-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R.)-3-{4~f3-(R)S)-fluoro-3-(6-rnéiboxyquino}in-4-yl)propyî]-l-[3-(4-n.iéthyl-phéiïy3}-prop-2-ynyj]-‘ •ipcridin-3-yl}pjopan-l-oique A'âdc(3R,4R)~3-{4-P-(isS>f:noro-3-(6-n)cük':.\y<}iBnoIiû-4-yî)pfOi)yI]· l-[3-(2-trifluoro-jBéthy]-pbényi)piop-2-yo ,!]-pip·. bciui 3-yl}propaa- i-oique 2 5 Acide (3R,4R)-3- {1- [3 -(R,S)· fluofO-3-(6-niéÜioxyqumolin-4-yi)propyl]-l -[3-(3-trifluoro- méihyl-phàiyl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4 - [(3R) S) -fluoro-3- (6-reniboxyquino} -in-4-yl) propyl] -1- [3- (4-ethyl) -acetyl] -3- -phelyl3-prop-2-ynyl] -opyridin-3-yl} pjopan-1-oic A'dc (3R, 4R) -3- {4-P- (isS) f: noro-3- ( 6-n) (1-yl) -3- (2-trifluoromethyl) -benzyl) pip-2-yl, piper). (3R, 4R) -3- {1- [3 - (R, S)) fluofO-3- (6-dihydroxy-4-yl) propyl] -l-3-yl} propanoic acid - [3- (3-Trifluoromethyl-phenyl) -prop-2-ynyl] -piperidin-3-yl} propan-1-ol

Acide (3R,4R)-3-{4-[3-(R,S)-iluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(4-trifiuoro-mé±yl-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Lluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethyl) - (3R, 4R) -3- {4- [3- (R, S) -Lluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethyl)} phenyl) -prop-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l -[3-(2-méthoxy- 3 0 phényl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (2-methoxyphenyl) -acid ) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R>3- {4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-(3-méthoxy-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxy-iminolin-4-yl) propyl] -1- [3- (3-methoxy-phenyl) -prop) acid -2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-méthoxy-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique 3 5 Acide (3R,4R)-3-{4-[3-(R,S)-iluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3,4-difluoro- phényl)-prop-2-ynyl]-piperidin-3 -yl }propan-1 -oique 120 22 142(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (4-methoxyphenyl) - acid prop-2-ynyl] -piperidin-3-yl} propan-1-oic acid (3R, 4R) -3- {4- [3- (R, S) -iluoro-3- (6-methoxyquinolin)} 4-yl) propyl] -1- [3- (3,4-difluorophenyl) prop-2-ynyl] -piperidin-3-yl} propan-1-oic 120 22 142

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,4-difluoro-phényl)-prop-2-ynyl]-piperidm-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-difluoro-phenyl) acid ) -prop-2-ynyl] -piperidm-3-yl} propan-l-oic acid

Acide (3R,4R>3-{4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3,4-dichloro-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4-dichlorophenyl) acid) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,3-dichloro-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (2,3-dichlorophenyl) -acid ) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,4-dichloro-phényl)-prop-2-ynyl]-piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-dichlorophenyl) -acid ) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,4,6-trichloro-phényl)-prop-2-ynyl]-piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (2,4,6-trichloro) -acid -phenyl) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(3,5-dichloro-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (3,5-dichlorophenyl) -acid ) -prop-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-chloro-3-fluoro-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3-fluoro) acid -phenyl) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-l-[3-(3-chlor<>-4-fluoro-phényI)-prop-2-ynyl]-piperidin-3-yI }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (3-chloro) -4) acid 1-fluoro-phenyl) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-iluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-chloro-4-fluoro-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Lluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4-fluoro) acid phenyl) -prop-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-chIoro-5-fluoro-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-5-fluoro) -acid phenyl) -prop-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-chloro-2-fluoro-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (4-chloro-2-fluoro) acid phenyl) -prop-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-(3-fluoro-4-méthyl-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1 - [3- (3-fluoro-4-methyl) - (3R, 4R) -3- -phenyl) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R_4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(4-chloro-3- trifluoromé±yl-phényl)-prop-2-ynyl]-piperidin-3-yl }propan-1 -oique(3R_4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (4-chloro-3-trifluoromethyl) -acrylic acid; -phenyl) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R.4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[3-(2-chloro-4- trifluorométhyl -phényl)-prop-2-vnvl] -piperidin-3 -yl} propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinin-4-yl) propyl] -1 - [3- (2-chloro-4-trifluoromethyl) -phenyl) -prop-2-yl] -piperidin-3-yl} propan-1-oic

Acide (3R.4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-chloro-5- trifluoromé±yl-phénvl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-5-trifluoromethyl) - ± yl-phenyl) -prop-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méîhoxyquinolin-4-yl)propyl]-1 -[3-(5-chloro-2- méthoxy-phényl)-prop-2-ynyl]-pipendin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (5-chloro-2-methoxy) -acidic acid -phenyl) -prop-2-ynyl] -pipendin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolinA-yl)propyl]-1 -[3-(3,5-bis- trifiuorométhyl-phényl)-prop-2-ynyl]-piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3,5-bis-trifluoromethyl-phenyl) ) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3,5-diméthyl- phényl)-prop-2-ynyl]-piperidin-3-yl }propan-1 -oique 143(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3,5-dimethylphenyl) -acid ) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-iluoro-3-(6-méthoxyquinoiin-4-yl)propyl]-1-(3-(2,4-dichloro-6-méthyl-phényl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Iluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (2,4-dichloro) -6-acid 1-methyl-phenyl) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(thien-2-yl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (thien-2-yl) - acid prop-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl3- l-[3-(5-chloro-thien-2-yl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-chloro-thien-2-) -acidic acid yl) -prop-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-chloro-thien-2-yl)-prop-2-ynyI]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-chloro-thien-2-yl) -acidic acid -yl) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,Syfluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(5-méthyl-thien-2-yl>prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R), Syfluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (5-methylthien-2-yl) acid) prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[3-(3-méthyl-tbien-2-yl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-tert-2-en) yl) -prop-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(thien-3-yl)-prop-2-ynyl]-piperidm-3-yl}propan- 1-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1 - [3- (thien-3-yl) - acid prop-2-ynyl] -piperidm-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-fhioro-3-(6-mé&amp;oxyquinolin-4-yI)propyl3-l-[3-(l-métbyl-pynol-2-yl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -fhioro-3- (6-methyloxy-4-yl) propyl] -1- [3- (1-methylbenzyl) -benzyl) -acryl-3- 2-yl) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-iluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-( 1 -méthyl-pyrrol-3-yl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Lluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (1-methyl-pyrrol-3) -acid yl) -prop-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-métiioxyquinolin-4-yl)propyl]-1 -[3-(thiazol-2-yl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methioxyquinolin-4-yl) propyl] -1 - [3- (thiazol-2-yl) - acid prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-mcthoxyquir>oEn-4-yl)propyl]-l-[3-(thiazol-4-yl)-prop-2-ynyi] -pipes idin-3 -yl} propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methyloxy) -I-en-4-yl) propyl] -1- [3- (thiazol-4-yl) -acid ) -prop-2-ynyi] -pipes idin-3-yl} propan-1 -oic

Acide (3R,4R)-3-{4-[3-(R,S)-fluoro-3-(6-inéthoxyquiiiolin-4-yl)i)rc!pyl]-]-[3-(thiazoi-5-yl)-prqp-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-ethoxyquinolin-4-yl) (1H) pyl] -] - [3- (thiazol-5) -acidic acid; yl) -prqp-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3Il,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyi]-1 -[3-( 1 -méthyl-imidazol-2-yl)-prop-2-ynyl]-piperidin-3-yl} propan-1 -oique(3 R, 4 R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (1-methyl-imidazol-2) -acidin -yl) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yI)propyl]-1 -[3-(3-méthyl-imidazol-4-yl)-prop-2-ynyl]-piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-methyl-imidazol-4) -acidazol -yl) -prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-méthyl-pyrazol-4-yl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-methyl-pyrazol-4) -acid yl) -prop-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyI]-1 -[3-(oxazol-2-yl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) - acid prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(oxazol-4-yl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (oxazol-4-yl) - acid prop-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(oxazol-5-yl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique 120 22 144'(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (oxazol-5-yl) - acid prop-2-ynyl] -piperidin-3-yl} propan-1-1 120 22 144 '

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridin-2-yl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (pyridin-2-yl) - acid prop-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-niéthoxyquinolin-4-yl)propyl]-1 -[3-(pyridin-3-yl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl) - acid prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridin-4-yl)-prqp-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (pyridin-4-yl) - acid prqp-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-2-yl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (pyrimidin-2-yl) - acid prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-4-yl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (pyrimidin-4-yl) - acid prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R.4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-5-yl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (pyrimidin-5-yl) - acid prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyra2in-2-yl)-prop-2-ynyl]-piperidin-3-yl}propan-l-oique(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (pyrazin-2-yl) - acid prop-2-ynyl] -piperidin-3-yl} propan-l-oic acid

Acide (3R4R)-3- {4-[3-(R,S)-fluoro-3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[3-(pyridazin-3-yl)-prop-2-ynyl]-piperidin-3-yl}propan-1 -oique(3R4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methyloxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) - acid prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridazin-4-yl)-prop-2-ynyl]-piperidin-3-yl }propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (pyridazin-4-yl) - acid prop-2-ynyl] -piperidin-3-yl} propan-1-oic

Acide (3R4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-phénylpropèn-2-yl]piperidin-3-yl} propan-1 -oique(3R4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3-phenylpropen-2-yl] piperidin-3-yl} propan-1-oic acid

Acide (3R,4R)-3- {4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-phénylbutèn-3-yl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4-phenylbuten-3-yl] piperidin-3-yl} propan-1 -ic acid

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-phényl-propèn-2-yl]piperidin-3-yl}propan-1 -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenyl-propen-2-yl] acid piperidin-3-yl} propan-1-oic

Acide (3R,4R)-3- {4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-phénylbutèn-3-yl] piperidin-3-yl}propan-l -oique(3R, 4R) -3- {4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4-phenylbuten-3-yl] piperidinic acid; 3-yl} propan-l-oic

Acide (3R,4R)-3- {4-[3-(RS)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-phénylpropèn-2-yl]piperidin-3-yl} propan-1 -oique(3R, 4R) -3- {4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylpropen-2-yl] piperidin-3- acid yl} propan-1 -oic

Acide (3R,4R)-3- {4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-phénylbutèn-3-yl]piperidin-3-yl }propan-1 -oique (3&amp;4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-phénylthio-éthyl] pipéridine (3R4R)-3-hydroxymétbyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-phénylthio-propyl]pipéridine > (3R4R)-3-hydroxyméthyl^-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2-fluorophénylîhio) éthyl]pipéridine x 120 2 2 145 (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2-fluorophénylthio) propyljpipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propylj-1 -[2-(3-fluorophénylthio)éthylj ipéridine 5 (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl j-1 -[3-(3-fluoropbénylthio) propyljpipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propylj-l-[2-(4-fluorophénylthio) éthyljpipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propylj-l-[3-(4-iluorophénylthio)10 propyljpipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl j-1 -[2-(2-chlorophénylthio)éthyljpipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propylj-l-[3-(2-chlorophénylÎhio) propyljpipéridine 15 (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propylj-l-[2-(3-chlorophénylthio)éthyljpipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propylj-l-[3-(3-chlorophénylthio) propyljpipéridine (3R,4R)-3-hydroxyméthyl-4-[3-{6-méthoxyquinolin-4-yl)propylj-1 -[2-(4-chlorophénylthio)20 éthyljpipéridine (3R,4R)-3-hydrox>TOéîhyl-4~f3~(6~roéib.o?7qp: noli.n-4-yl)pj.Opylj" 1 -[3-(4-cblorophôiylthio)propyljpipéridine (3R,4R)-3'-hydroxyméthyî-4 [3~(6 nfôibc'<yqi<b,Ci’in-4-yl)ps-opyIj-l-[2-(2-méthylphénylthio)étliyîjpipcridine 25 (3R,4R)-3-bydroxymétbyM-[3-(6-méthoxyqumolin-4-yI)piopyl]-l-[3-(2-méthylphénylthio)propyljpipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-ftiéthoxyquinolin-4-yl)propylj-l-[2-(3-méthylphénylthio) éthyljpipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-méthylphénylthio)3 o propyljpipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propylj-l-[2-(4-méthylphénylthio) éthyljpipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propylj-l-[3-(4-méthylphénylthio) propyljpipéridine 3 5 (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propylj-1 -[2-(2-trifluorométhyl- phénylthiojéthyljpipéridine >120 2 2 146 (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2-trifluorométhyl- phénylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-inéthoxyquinolin-4-yl)propyl]-l-[2-(3-trifluorométhyl- phénylthio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-trifluorométhyl-phénylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(4-trifluorométhyl-phénylthio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-niéthoxyquinolin-4-yl)propyl]-1 -[3-(4-tiifluorométhyl-phénylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2-méthoxyphényltbio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2-niéthoxyphényl±io) propyljpipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(3-méthoxyphénylthio) éthyljpipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propylJ 1 -[3-(3-méthoxyphénylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propylJ-1 -[2-(4-méthoxyphénylthio)éthyljpipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-métho?cyquinolin-4-yl)propylJ-1 -[3-(4-méthoxyphénylthio)propyljpipéridine (3R,4R)-3-hydroxyméthyl^4-[3-(6-mélhoxyquinolin-4-yl)propyl]-l-[2-(thien-3-yl)thioéthyl] pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propylJ-l-[3-(thien-3-yl)thiopropyl] pipéridine(3R, 4R) -3- {4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4-phenylbuten-3-yl] piperidinic acid; 3-yl} propan-1-oic (3 &amp; 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2-phenylthioethyl] piperidine (3R4R) - 3-Hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylthio-propyl] piperidine> (3R4R) -3-hydroxymethyl- [3- (6-methoxyquinolin-4) -yl) propyl] -1- [2- (2-fluorophenylthio) ethyl] piperidine x 120 2 2 145 (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] 1- [3- (2-fluorophenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluorophenylthio) ethyl] peridine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoropbenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4 [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-fluorophenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl)] propyl-1- [3- (4-fluorophenylthio) propyl] piperidine (3R, 4R) -3-Hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-chlorophenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4-ene [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenyl) halo) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) ) propyl] -1- [2- (3-chlorophenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenylthio)) (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-chlorophenylthio) ethyl] piperidine (3R, 4R) -3-hydroxyl-propyl] -piperidine 4 - [3- [3- (3- (4-chlorophenylthio) propyl] piperidine (3R, 4R) -3'-hydroxymethyl-4-yl [6-butyl-4-yl] 3 '(6') - [2- (2-methylphenylthio) ethyl) pyridine (3R, 4R) -3-hydroxymethyl-3- [6 (6)] - (6-methyl-1-yl) methoxy-iminolin-4-yl) piopyl] -1- [3- (2-methylphenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [ 2- (3-methylphenylthio) ethyl (3R, 4R) -3-Hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenylthio) 3-propyl] piperidine (3R, 4R) -3-hydroxymethyl 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (4-methylphenylthio) ethyl] piperidine (3 R, 4 R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4- yl) propyl] -1- [3- (4-methylphenylthio) propyl] piperidine 3 (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-propyl)] - -trifluoromethylphenylthio] ethylpiperidine> 120 2 2 (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethylphenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethylphenylthio) ethyl] piperidine (3R, 4R) -3 4-Hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethyl-phenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (4-trifluoromethyl-phenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-nitro) Ethoxyquinolin-4-yl) propyl] -1- [3- (4-tifluoromethyl-phenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-Methoxyphenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenyl) -1- [2- (2-methoxyphenyl) benzyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methoxyphenylthio) ethyl] piperidine (3R, 4R) -3-propyl-piperidine hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin) 4-yl) propyl] -1- [2- (4-methoxyphenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-Methoxyphenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxy-4-yl) propyl] -1- [2- (thien-3-yl) thioethyl] piperidine (3R) 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) thiopropyl] piperidine

(3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-vl)propyl]-l-[2-(iur-2-yl)thioéthylJ pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propylJ-l-[3-(fur-2-yl)thiopropyl] pipéridine(3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (iur-2-yl) thioethyl] piperidine (3R, 4R) -3-hydroxymethyl 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (fur-2-yl) thiopropyl] piperidine

(3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propylJ-l-[2-(fur-3-yl)thioé±ylJ pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin^l-yl)propyl]-l-[3-(fur-3-yl)thiopropyl]pipéridine ’ (3R,4R)-3-hydroxymé±yl-4-[3-(6-mé±oxyquinolin-4-yl)propyl]-l-[2-(thiazol-2-yl)thioéthyl] pipéridine x 120 2 2 147 (3R,4R)-3-hydroxyméihyl-4-[3-(6-niéth.oxyquinolin-4-yl)propyl]-l-[3-(thiazol-2-yl)üiio- propyljpipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(oxazol-2-yl)thioéthyl]pipéridine 5 (3R,4R)-3-hydroxyméthyl-4-[3-(6-niéthoxyquinolin-4-yl)propyl]-1 -[3-(oxazol-2-yl)thio- propyljpipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl j-1 -[2-(pyridin-2-yl)thio-éîhyljpipéridine (3R,4R)-3-hydroxyméthyl^4-[3-(6-méthoxyqumoIin-4-yl)propyl]-1 -[3-(pyridin-2-yl)thio-lo propyljpipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyridin-3-yl)thio-éthyljpipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(pyridin-3-yl)thio- propyljpipéridine 15 (3R,4R)-3-hydroxyméthyl-4-[3“(6-méthoxyquinolin-4-yl)propyl]-l -[2-(pyridin-4-yl)thio-éthyljpipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-inéÜioxyquinolin-4-yl)propylJ- l-[3-(pyridin-4-yl)thio-propyljpipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propylJ-l-[2-(pyrimidin-2-yl)thio-20 éthyljpipéridine (3R,4R)-3-hydroxymélbyl-4-[3-(6-méfhox)'rpirîolin-4-yI)propyl]-î-[3-(pyi-iniidin-2-yl)thio- propyljpipéridine (3R,4R) -3-Iîydroxyt»étbyl-ri-[3-(6 méthoxyq: inolin·/ -yl)pre· iyl J-1 · [2-(pyrarin -2-yl)thio-éthy 1] pipe< idine 25 (3R/R)~3 -hydro>ym5Æyl-4[3-(6-inéltioxyqimiolin-4-yl)propyl]-l-[3-(pyjKzin-2-yl)thio- propyljpipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(pyridazin-3-yl)thio- éthyljpipéridine (3R,4R)-3-hydroxyméthyl4-[3-(6-méthoxyquinolin-4-yl)propylJ-l-[3-(pyridazin-3-yl)thio-3 0 propyljpipéridine (3R,4R)-3-hydroxyméthyl^-[3-(6-méthoxyquinolin-4-yl)propyl j-1 -[2-(pyrida2in-4-yl)thio-éthyljpipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(pyridazin-4-yl)thio- propyljpipéridine 35 (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propylJ-l-[3-phényl-prop-2-ynylJ-pipéridine 120 2 2 148 (3R,4R)-3-hydroxyméthyl^4-[3-(6-méthoxyqumolin-4-yl)prcpyl]-1 -[3-(2-fluoro-phényl)-prop-2-ynyl]-pipéridme (3R,4R)-3-hydroxyméthyl-4-[3-(6-méîhoxyqumolin-4-yl)prOpyl]-1 -[3-(3-fluoro-phényl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[3-(4-fluoro-phényl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-chloro-phényl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyqumolm-4-yl)propyl]-l-[3-(3-chloro-phényl)- prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[3-(4-chloro-phényl)-prop-2-ynyl]-pipéridme (3R,4R)-3-hydroxyméÜiyl-4-[3-(6-méthoxyqumolm-4-yl)propyl]-l-[3-(2-méthyl-phény])- prop-2-ynyl]-pipéridme (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-méthyl-phényl)- prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(4-méthyl-phényl)- prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2-trifluorométhyl- phényl)-prop-2-ynyl]-pipéridme (3R,4R)-3-hydroxyméthyl-4-[3-(6-mé±oxyqumolm-4-yl)piOpyl]-1 -[3-(3-trifluorométhyl-phényl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl^l-[3-(6-mé±oxyquiiiolin-4-yl)propyl]-1 -[3-(4-ttifluorométhyl-phényl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxymé±yl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2-méthoxy-phényî)- prop-2-ynyl]-pipéridine (3R,4R)-3-hydrox>'mé±yl^}-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-méthoxy-phényl)- prop-2-ynyl]-pipéridine (3R.4R)-3-hydrox>Tnéthyl-4-[3-(6-méthoxyquinolin^-yl)propyl]-l-[3-(4-méthox\'-phënyl)- prop-2-ynyl]-pipéridine (3RT4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thien-2-yl)-prop-2- ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-mé±oxyquinolin-4-yl)propyl]-l-[3-(thien-3-yl)-prop-2- ynyl]-pipéridine (3R,4R)-3-hydroxyméÎhyl-4-[3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(îhiazol-2-yl)-prop-2 ynyl]-pipéridine 12 0 2 2 149 (3R4R)-3-hydroxymétiiyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(lhiazol-4-yl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl j-1 -[3-(thia2ol-5-yl)-prop-2-ynylj-pipéridine (3R,4R)-3-hydroxyméîhyl-4-[3-(6-méthoxyquinolin-4-yl)propylj-l-[3-(oxazol-2-yl)-prop-2- ynylj-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-xnéthoxyqumolin-4-yl)propyl]-l-[3-(oxa2ol-4-yl)-prop-2- ynylj-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolm-4-yl)propyl]-l-[3-(oxazol-5-yl)-prop-2- ynylj-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méûioxyquinolin-4-yl)propylj-l-[3-(pyridin-2-yl)-prop-2- ynylj-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propylj-1 -[3-(pyridin-3-yl)-prop-2-ynylj-pipéridine (3R,4R)-3-hydroxyméthyl~4'[3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(pyridin-4-yl)-prop-2- ynylj-pipéridine (3R,4R)-3-hydroxyméîhyl-4-[3-(6-méthoxyquinolin-4-yl)propylj-l-[3-(pyrimiclin-2-yl)-prop- 2-ynylj-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méÜioxyquinolin-4-yl)propylj-l-[3-(pyrazin-2-yl)-prop-2- ynylj-pipéridine (3R4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolm-4-yl)propylj-l-[3-(pyridazin-3-yl)-prop- 2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propylj-1 -[3-(pyridazin-4-yl)-prop-2-ynylj-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydiOxy-3-(6-méthoxyquinolin-4-yl)propylj-l-[2- phénylthio-éthyljpipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(RS)-hydroxy-3-(6-méthoxyquinolin-4-yl)propylj-1 -[3-phénylthio-propyljpipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(RS)-hydroxy-3-(6-méthoxyqninolin-4-yl)propylj-l-[2-(2- fluorophénylthiojéthyljpipéridine (3R,4R)-3-hydroxyméthyî-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propylj-l-[3-(2- fiuorophénylthiojpropyljpipéridine (3R4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propylj-l-[2-(3- fluorophénylthiojéthyljpipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(RS)-hydroxy-3-(6-méthoxyquinolm-4-yl)propylj-l-[3-(3- fluorophénylthiojpropyljpipéridme 120 2 2 150 (3R,4R>3-hydroxymétfayl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquiiiolm-4-yl)propyl]-l-[2-(4- fluorophénylthio)éthyl]pipéridme (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(4- fluorophénylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-inéthoxyquinolin-4-yl)propyl]-1 -[2-(2-chlorophénylt&amp;o)éthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumoIm-4-yl)propyl]-1 -[3-(2-cHorophénylthio)propyl]pipéridme (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3-chlorophénylthio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-chlorophénylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(4-chlorophénylthio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydrüxy-3-(6-méthoxyquinoJin-4-yl)propyl]-1 -[3-(4-chlorophénylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl^l-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2-méthylphénylthio)éthyl]pipéridine (3R,4R)-3-hydroxymélhyl-4-[3-(R,S)-hydroxy-3-(6-mé±oxyqumolin-4-yl)propyl]-1 -[3-(2-méthylphénylthio)propyl]pipéridiiie (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(3- méthylphénylthio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolm-4-yl)propyl]-l-[3-(3- méîhylphénylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl ^4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[2-(4-méîhylphénylthio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(4- méthylphénylthio)propyl]pipéridme (3R,4R)-3-hydroxyméthyl-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin^-yl)propyl]-l-[2-(2- trifluorométhylphénylthio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthox7quinolin-4-yl)propyl]-l-[3-(2- trifluorométfaylphénylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl^l-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(3- trifluorométhylphénÿlthio)éthyl]pipéridine (3R_4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin^-yl)propyl]-l-[3-(3- trifluorométhylphénylthio)propyl]pipéridine 120 2 2 151 (3R,4R)-3-hyâroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(4-trifluorométhylphénylthio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(4- trifluorométhylphénylthio)propyl]pipéridine 5 (3R,4R)-3-hydroxyméÛiyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[2-(2- méthoxyphénylthio)éthyl]pipéridme (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin^-yl)propyl]-l-[3-(2- méthoxyphénylthio)propyl]pipéridme (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-l-[2-(3-10 méthoxyphénylüiio)éthyl]pipéri(liûe (3R,4R)-3-hydroxyméîhyl-4-[3-(R,S)-hyâroxy-3-(6-méthoxyqumolm-4-yl)propyl]-l-[3-(3- méthoxyphénylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[2-(4-méthoxyphénylthio)éthyl]pipéridine 15 (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-{6-méthoxyqumolm-4-yl)propyl]-1 -[3-(4- méthoxyphéaylthio)propyl]pipéridme (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2- (thien-3-yl)thioéthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-20 (thien-3-yl)thiopropyl]pipéridine (3R,4R)-3-hydroxytnéthyl-4-[3-(R,S>-hydroxy-3-(6-mélhoxyquinoUn-4-yl)propyl]-l-[2-(fur· 2-yl)tbioéthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl3-l-[3-(fiir· 2- yl)thiopropyl]pipéridine 2 5 (3R,4R}-3-hydroxyméthyl-4”[3-(R)S)-hydroxy-3-(6-méthoxyquinoliii-4-yl)propyl]-1 -[2-(fur 3- yl)thioéthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(fur3-yl)thiopropyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3'(6-méthoxyquinolin-4-yl)propyl]’ 1 -[2-30 (thiazol-2-yl)thioéthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(thiazol-2-yl)thiopropyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)*hydroxy-3-(6-xnéihoxyquinolm-4-yl)propyl]-l-[2- (oxazol-2-yl)thioéthyl]pipéridine 3 5 (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3- (oxazol-2-yl)thiopropyl]pipéridine 120 22 152 (3R,4R)-3-hydroxyinéthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolm-4-yl)propyl]-l-[2- (pyridin-2-yl)thioéthyI3pipéridme (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquiQoIin-4-yl)propyl]-l-[3- (pyridin-2-yl)thiopropyl]pipéridme (3R,4R)-3-hydroxyméthyl^4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[2-^yridin-3-yl)thioéthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-mé±oxyquinoliQ-4-yl)propyl]-1 -[3-^yridin-3-yl)thiopropyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-niéthoxyqumolm-4-yl)propyl]-1 - [2-(pyridin-4-yl)tfaioéthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-l-[3- (pyridin-4-yl)thiopropyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2- ^yrimidin-2-yl)thioéthyl]pipéridine (3R,4R)-3-hydroxyméthyl^-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]- ] -[3-(pyrimidin-2-yl)tbiopropyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydro?cy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyrazin -2-yl)thioéthyl]pipéridine (3R,4R)-3-hydroxyméthyl^l-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3- (pyrazm-2-yl)thiopropyl]pipéridine (3R.4R)-3-hydroxyméthyl^-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2- (p\Tidazin-3-yl)thioéthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[3-(pyridazm-3-yl)thiopropyl]pipéridine (3R,4R)-3-hydroxyTOéthyl^-[3-(R,S)-hydroxy-3-(6-méthoxyquinoIin-4-yl)propyl]-l-[2- (pyridazin-4-yl)thioéthyl]pipéridme (3R_4R)-3-hydroxy'mé±yl^-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin^-yl)propyl]-l-[3- (p\Tidazin^-yl)thiopropyl]pipéridine (3K4R)-3-hydroxy,mélhyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3- phényl-prop-2-ynyl]-pipéridine (3R.4R)-3-hydroxyméthyl^l-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl3-l-[3-(2- fluoro-phényl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydro?cy-3-(6-méthoxyquinolm-4-yl)propyl]-l-[3-(3-fluoro-phényl)-prop-2-vnyl]-pipéridine * (3R4R)-3-hydroxyméthyl-4-[3-(R_S)-hydroxy-3-(6-méthox\'quinolin-4-yl)propyl]-l-[3-(4- fluoro-phényl)-prop-2-ynyl]-pipéridine 1 20 2 2 153 (3R,4R)-3-hydroxymé&amp;yl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquiiiolin-4-yl)propyl]-l-[3-(2- chloro-phényl)-prop-2-ynyl]-pipéridme (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquiiiolin-4-yl)propyl]-l-[3-(3- chlon>phényl)-prop-2-ynyl]-pipéridine 5 (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-métho?cyquinolin-4-yl)propyl]-1 -[3-(4-chloro-phényl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R1S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(2-méthyl-phényl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyî-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yi)propyl]-1 - [3-(3-io méthyl-phényl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hyâroxy-3-(6-méthoxyqumoIin-4-yl)propyl]-l-[3-(4- méthyl-phényl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-(2-trifluorométhyl-phényl)-prop-2-ynyl]-pipéridine 15 (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-triiluorométhyl-phényl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(4- trifluorométhyl-phényl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3 -(2-20 méthoxy-phényl)-prop-2-ynyl]-pipéridiiie (3R,4R)-3-hydiOxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl3-l-[3-(3- méthoxy-phényl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(4- méthoxy-phényl)-prop-2-ynyl]-pipéridine 2 5 (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyqt±iolm-4-yl)propyl]-1 -[3- (thien-2-yl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl^-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-(thien-3-yl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolm-4-yl)propyl]-1 -[3- 3 o (thiazol-2-yl)-prop-2-ynyl]-pipéridme (3R,4R)-3-hydroxymétbyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(thiazol-4-yl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoIin-4-yl)propyl]-l-[3- (thiazol-5-yl)-prop-2-ynyl]-pipéridine 3 5 (3R,4R)-3-hydroxyxnéthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3- (oxa2ol-2-yl)-prop-2-ynyl]-pipéridine 120 2 2 154 (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-l-[3- (oxazol-4-yl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)prOpyl]-1 -[3-(oxazol-5-yl)-prop-2-ynyl]-pipéridine (3R,4R>3-hydroxyméthyl-4-[3-(R,S>hydroxy-3-(6-méthoxyqumoIin-4-yl)propyl]-l-[3- (pyridin-2-yl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridin-3-yl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(pyridin-4-yl)-prop-2-ynyl]-pipéridine (3R4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyrimidin-2-yl)-prop-2-ynyl]-pipéridine (3R.4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthioxyquinolin-4-yl)propyl]-1 -[3-(pyrazin-2-yl)-prop-2-ynyl]-pipéridine (3R4R)-3-hydroxyméthyl^4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridazin-3-yl)-prop-2-ynyl]-pipéridine (3R4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3- (pyridazin-4-yl)-prop-2-ynyl]-pipéridine (3R4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-phénylthio-éthyljpipéridine (3R4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolm-4-yl)propyl]-l-[3- phénvlthio-propyl]pipéridine (3R4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2- fluorophénylthio)é±yl]pipéridine (3R,4R)-3-hydrox5'méthyl-4-[3-(R.S)-fluoro-3'(6-méthox}’quinolin^-yl)propyl]-l-[3-(2- fluorophénylthio)propyl]pipéridine (3R4R)-3-hy<koxyméthyl^[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(3- fluorophénylthio)étb\’l]pipéridine (3R4R)-3-hydrox\'méthyl-4-[3-(R,S)-fluoro-3-(6-méihox\c[uinolin^-yl)propyl]-l-[3-(3- fluorophénylthio)propyl]pipéridine (3R4R)-3-hydroxyméthyl^-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(4- fluorophénylthio)éthyl]pipéridine (3R4R)-3-hydroxymé±yl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(4- fluorophénylîhio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl^-[3-(R,S)-fluoro-3-(6-méthoxyquinolin^-yl)propyl]-l-[2-(2- chlorophénylthio)é±yl]pipéridine 12022 155 (3R,4R)-3-hydroxyméthyl-4-[3'(R,S)-iluoro-3-(6-méthoxyquinolm-4-yl)propyl]-l-[3-(2- chlorophényltbio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl^-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)prcpyl]-l-[2-(3- chlorophénylthio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-inéthoxyquinolin-4-yl)propyl]-l-[3-(3- chlorophénylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méÜioxyquinoîin-4-yl)propyl]-l-[2-(4- chlorophénylthio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinoliD-4-yl)propyl]-1 -[3-(4-cHorophénylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 - [2-(2-méthylphénylthio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(2- méthylphénylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-l-[2-(3- méthylphénylthio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6~méthoxyquinolin-4-yl)propyl]-l-[3-(3- méthylphényltbio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[2-(4-méthylphénylttiio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-l-[3-(4- méthylphénylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-l-[2-(2- trifluorométhylphénylthio)éûiyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolm-4-yl)propyl]-l-[3-(2- trifluorométhylphénylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthy]-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(3- trifluorométhylphénylthio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3- trifluorométhylphénylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(4- trifluorométhylphénylthio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-trifluorométhylphénylthio)propyl3pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-iluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2“(2- méthoxyphénylthio)éthyljpipéridine 120 2 2 156 (3R,4R)-3-hydroxyniéthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-méthoxyphénylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinoliii-4-yl)propyl]-1 -[2-(3-méthoxyphénylthio)étfayl]pipéridme 5 (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 - [3 -(3- méthoxyphénylthio)propyl]pipéridine (3R,4R)-3-hydroxymé±yl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 - [2 -(4-méthoxyphénylthio)éthyl]pipéridine (3R,4R)-3-hydroxymé±yl4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4- 1 o méthoxyphénylthio)piOpyl]pipéridine (3R,4R)-3-hydroxymélhyl-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[2-(thien-3-yl)thioéthyl]pipéridme (3R,4R)-3-hydroxyméthyl^4-[3-(R,S)-fluon>3-(6-méthoxyquhiolin-4-yl)propyl]-1 -[3-(thien-3-yl)thiopropyl]pipéridine 15 (3R,4R)-3-hydroxymé±yl^4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[2-(fur-2-yl)thioéthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyqumoliii-4-yl)propyl]-1 -[3-(fur-2-yl)thiopropyl]pipéridine (3R,4R)-3-hydroxymé±yl-4-[3-(R,S)-fluoro-3-(6-méîhoxyquinolm-4-yl)propyl]-1 -[2-(fur-3 - 2 o yl)thioéthyl]pipéridme (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinoIin-4-yl)propyl]-1 -[3-(fur-3-yl)thiopropyl]pipéridme (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(thiazol 2-yl)thioéthyl]pipéridine 2 5 (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(thiazol 2-yl)thiopropyl]pipéridine (3Rt4R)-3-hydroxymétbyl^!-[3-(RtS)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-l-[2-(oxa2ol 2-yl)thioéthyl]pipéridine (3R,4R)-3-hydroxymé±yl-4-[3-(R,S)-fluoro-3-(6-méthox)'quinolin-4-yl)propyl]-l-[3-(oxa2ol 3 o 2-yl)thiopropyl]pipéridine (3R-4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyridin-2-yl)thioéthyl]pipéridine (3R,4R)-3-hydroxyméthyl^4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridin-2-yl)thiopropyl]pipéridine 3 5 (3R,4R)-3-hydroxyméthyl^-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyridin-3-yl)thioeïhyl]pipéridme 120 22 157 (3R,4R)-3'hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-l-[3- (pyridin-3-yl)thiopropyl]pipéridme (3R,4R)-3-hydro?cyméthyl-4-[3-(R,S)-iluor(>3-(6-métiioxyquinolin-4-yl)propyl]-1 -[2- ^yridin-4-yl)thioéthyl]pipéridine 5 (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin^-yl)propyl]-1 -[3- (pyridin-4-yl)thiopropyl]pipéridine (3R,4R>3-hydroxyméthyl-4-[3-(R,S)-fluon>-3-(6-méthoxyqumolm-4-yl)propyl]-l-[2- ^yrimidin-2-yl)tMoéthyl]pipéridme (3R,4R)-3-hydroxyméÜiyl-4-[3-(R,S)-iluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -β-ίο ^yrimidm-2-yl)thiopropyl]pipéridine(3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (fur-3-yl) thio] -yl] piperidine (3R, 4R) -3- hydroxymethyl-4- [3- (6-methoxyquinolin-1-yl) propyl] -1- [3- (fur-3-yl) thiopropyl] piperidine '(3R, 4R) -3-hydroxymethyl-4- [ 3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thiazol-2-yl) thioethyl] piperidine x 120 2 2 147 (3R, 4R) -3-hydroxymethyl-4- [3] (6-Methyloxyquinolin-4-yl) propyl] -1- [3- (thiazol-2-yl) -1'-i-propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin)] 4-yl) propyl] -1- [2- (oxazol-2-yl) thioethyl] piperidine 5 (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] - 1 - [3- (oxazol-2-yl) thio-propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin)]; 2-yl) thio-ethylpiperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinin-4-yl) propyl] -1- [3- (pyridin-2-yl) thio-propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-3-yl) thio-ethyl] piperidine (3R, 4R) -3- hydroxymethyl 1- [4- (3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl) thio-propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3 " (6-Methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-4-yl) thio-ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-acetioxyquinolin-4-yl) ) propyl-1- [3- (pyridin-4-yl) thio-propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- pyrimidin-2-yl) thio-20-ethylpiperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxy) pyrimidin-4-yl) propyl] -3- [3- (pyi-iminidin)]; 2-yl) thio-propyl-piperidine (3R, 4R) -3-hydroxyethylbenzyl [3- (6-methoxy) -inolin-1-yl) preyl] -1- [2- (pyrrino-2-yl) ) thio-ethyl 1] piperidin (3R / R) -3-hydroxy-ym5-yl [3- (6-ineltioxy-iminolin-4-yl) propyl] -1- [3- (py) -Kin-2-yl) thio-propyl-piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridazin-3-yl) thio-ethyl] piperidine (3R, 4R) 3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-3-yl) thio-propyl] piperidine (3R, 4R) -3-hydr oxymethyl- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-4-yl) thio-ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6) Methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4-yl) thio-propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl-1- [3-phenyl-prop-2-ynyl] -piperidine 1,128 (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquolin-4-yl) propyl] -1- [ 3- (2-Fluoro-phenyl) -prop-2-ynyl] -piperidin (3R, 4R) -3-hydroxymethyl-4- [3- (6-methyloxy-iminolin-4-yl) propyl] -1- [3- (3-Fluoro-phenyl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluoro-phenyl) -prop-2-ynyl] -piperidine 1-fluoro-phenyl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-1-chlorophenyl) -propionic acid] phenyl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyqumol-4-yl) propyl] -1- [3- (3-chlorophenyl) -phenyl) -prop-2-ynyl] -piperidine ) - prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenyl)) prop-2-ynyl] -piperidin (3R, 4R) 3-hydroxymethyl-4- [3- (6-methoxyqumol-4-yl) propyl] -1- [3- (2-methyl-phenyl) -prop-2-ynyl] -piperidin (3R, 4R) - 3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methyl-phenyl) -prop-2-ynyl] -piperidine (3R, 4R) -3- hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methyl-phenyl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl- 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethyl-phenyl) -prop-2-ynyl] -piperidin (3R, 4R) -3-hydroxymethyl-4- [3- (6-Methylmolm-4-yl) p-pylyl] -1- [3- (3-trifluoromethyl-phenyl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl- [3- (6-Methyl-quinolin-4-yl) propyl] -1- [3- (4-tifluoromethyl-phenyl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl. 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxy-phenyl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxyl N- [1- (3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxy-phenyl) prop-2-ynyl] -piperidine (3R, 4 R) -3-hydrox > Tnéthyl-4- [3- (6-methoxyquinolin ^ -yl) propyl] -l- [3- (4-Methoxy-phenyl) -prop-2-ynyl] -piperidine (3RT4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien) 2-yl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thienes) 3-yl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxy-iminolin-4-yl) propyl] -1- [3- (1-thiazol-2-yl) -3-yl) -piperidine 2-ylyl) -prop-2-ynyl] -piperidine 12 (2R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-thiazol-4-yl) 2-yl) propyl] -2- (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thia) -ol-5-yl] -piperidine ) -prop-2-ynylpiperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-2-yl) prop) 2-ynylpiperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquolin-4-yl) propyl] -1- [3- (oxa-2-yl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinol-4-yl) propyl] -1- [3- (oxazol-5-yl) -prop-2-ynyl] -piperidine ( 3R, 4R) -3-hydroxymethyl-4- [3- (6-méûioxyquinolin-4-yl) propylj-l- [3- (pyr idin-2-yl) -prop-2-ynylpiperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3- Yl) -prop-2-ynylpiperidine (3R, 4R) -3-hydroxymethyl-4 '[3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-4-yl)] prop-2-ynylpiperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2-yl) prop-2- (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) prop-2-ynyl] piperidine ( 3R4R) -3-hydroxymethyl-4- [3- (6-methoxyquinol-4-yl) propyl] -1- [3- (pyridazin-3-yl) -prop-2-ynyl] -piperidine (3R, 4R) - 3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazin-4-yl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl- 4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-phenylthio-ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- ( RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-phenylthio-propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (RS) -hydroxy-3- ( 6-méthoxyqninolin-4-yl) pr opyl [1- [2- (2-fluorophenylthio] ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -I- [ 3- (2-fluorophenylthio) propyl] piperidine (3R4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluorophenylthio] ethyl] piperidine ( 3R, 4R) -3-hydroxymethyl-4- [3- (RS) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (3-fluorophenylthio] propyl] piperide 120 2 2 150 (3R, 4R) > 3-Hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquiolam-4-yl) propyl] -1- [2- (4-fluorophenylthio) ethyl] piperidin (3R, 4R) 3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (4-fluorophenylthio) propyl] piperidine (3R, 4R) 3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-chlorophenyl) -0-ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinim-4-yl) propyl] -1- [3- (2-chlorophenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-méthoxyquinolin- 4-yl) propyl] -1- [2- (3-chlorophenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin) 4-yl) propyl] -1- [3- (3-chlorophenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin) 4-yl) propyl] -1- [2- (4-chlorophenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydryl-3- (6-methoxyquinoline) 4-yl) propyl] -1- [3- (4-chlorophenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl [1- [3- (R, S) -hydroxy-3- (6-methoxyquinolin)] 4-yl) propyl] -1- [2- (2-methylphenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methyl) oxyqumolin-4-yl) propyl] -1- [3- (2-methylphenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6- Methoxyquinolin-4-yl) propyl] -1- [2- (3-methylphenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6- Methoxyqumol-4-yl) propyl] -1- [3- (3-methylphenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6- méthoxyqumo lin-4-yl) propyl] -1- [2- (4-methylphenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6- Methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenylthio) propyl] piperidin (3R, 4R) -3-hydroxymethyl-4- [3- (RS) -hydroxy-3- (6-methoxyquinoline) -yl) propyl] -1- [2- (2-trifluoromethylphenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxy) quinolin-4 1-propyl] -1- [3- (2-trifluoromethyl) phenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl [1- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4 -yl) propyl] -1- [2- (3-trifluoromethylphenylthio) ethyl] piperidine (3R4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-1-yl)) propyl] -1- [3- (3-trifluoromethylphenylthio) propyl] piperidine 120 (3R, 4R) -3-hyabroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin)] 4-yl) propyl] -1- [2- (4-trifluoromethylphenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin) 4-yl) propyl] -1- [3- (4-trifluoromethylphenylthio) propyl ] Piperidine 5 (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [2- (2-methoxyphenylthio)] ethyl] piperidin (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-2-yl) propyl] -1- [3- (2-methoxyphenylthio) propyl] ] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxy-iminolin-4-yl) -propyl] -1- [2- (3-methoxyphenyl) piperidin) ethyl] piperoyl (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hyroxy-3- (6-methoxy-4-methyl-4-yl) propyl] -1- [3- (3- methoxyphenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [2- (4- Methoxyphenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyqumol-4-yl) propyl] -1- [3- (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methoxyphenylthio) propyl] piperidin 3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-yl) thioethyl] piperidine (Thien-3-yl) th iopropyl] piperidine (3R, 4R) -3-hydroxyethyl-4- [3- (R, S) -hydroxy-3- (6-methyloxyquinolin-4-yl) propyl] -1- [2- (fur 2- (3R, 4R) -3-Hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (fiir · 2 (yl) thiopropyl] piperidine (5R, 4R) -3-hydroxymethyl-4 "[3- (R) S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-yl) thioethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3 - (fur3-yl) thiopropyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3 '(6-methoxyquinolin-4-yl) propyl] -1 - [2] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1 -30 (thiazol-2-yl) thioethyl] piperidine [3- (Thiazol-2-yl) thiopropyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-xynoxyquinol-4-yl) propyl] 1- [2- (oxazol-2-yl) thioethyl] piperidine 3 (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4- yl) propyl] -1- [3- (oxazol-2-yl) thiopropyl] piperidine (22R, 4R) -3-hydroxy-ethyl-4- [3- (R, S) -hydroxy-3- (6-methoxy-imin-4-yl) -propyl] -1- [2- (pyridin-2-one) (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxy-4-yl-4-yl) -propyl] -1- [3- (pyridin-2-yl) thioethyl) piperidin yl) thiopropyl] piperidin (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [2-] yridine 3-yl) thioethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methyloxyquinol-4-yl) propyl] -1 - [3] (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxy-4-yl) propyl] -1-yitrin-3-yl) thiopropyl] piperidine [2- (pyridin-4-yl) t-aminoethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] - 1- [3- (pyridin-4-yl) thiopropyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] 1- (2-ylmidin-2-yl) thioethyl] piperidine (3R, 4R) -3-hydroxymethyl- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl)] propyl] -] - [3- (pyrimidin-2-yl) tbiopropyl] piperidine (3R, 4R) -3-hydrox Methyl-4- [3- (R, S) -hydro-cy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrazin-2-yl) thioethyl] piperidine (3R, 4R) ) -3-hydroxymethyl-1- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazol-2-yl) thiopropyl] piperidine (3R) 4R) -3-hydroxymethyl- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (p-tidazin-3-yl) thioethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazm-3-) yl) thiopropyl] piperidine (3R, 4R) -3-hydroxy-ethyl-N - [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridazin-4) (3R-4R) -3-hydroxy-methyl] -1- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-1-yl) propyl] -1- [3- (p-methyl) piperidin) [3-thiazolyl] thiopropyl] piperidine (3K4R) -3-hydroxy, methyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3] phenyl-prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl-1- [3- (R, S) -hydroxy-3- (6-methoxyquolin-4-yl) propyl] -1- [ 3- (2-Fluoro-phenyl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) ) -hydro-cy-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (3-fluoro-phenyl) -prop-2-yl] -piperidine * (3R4R) -3-hydroxymethyl- 4- [3- (R-S) -hydroxy-3- (6-methoxy-quinolin-4-yl) propyl] -1- [3- (4-fluoro-phenyl) -prop-2-ynyl] -piperidine 1 (2R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2H) -3- (3R, 4R) -3-hydroxymethyl; (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -piperidine (chloro-phenyl) -prop-2-ynyl] -piperid] 1- [3- (3-Chlon-phenyl) -prop-2-ynyl] -piperidine 5 (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3 (6 Methylcyquinolin-4-yl) propyl] -1- [3- (4-chloro-phenyl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R1S) ) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (2-methyl-phenyl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl-4 [3- (R, S) -hydroxy-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (3-methyl-phenyl) -prop-2-ynyl] -piperidine (3R) 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxy-4-quinolyl) propyl] -1- [3- (4-methylphenyl) -p) rop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (2R-Trifluoromethyl-phenyl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) ) propyl] -1- [3- (3-triiluoromethyl-phenyl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-Methoxy-iminolin-4-yl) propyl] -1- [3- (4-trifluoromethyl-phenyl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R) S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3 - (2-methoxy-phenyl) -prop-2-ynyl] -piperidine (3R, 4R) -3- HydIxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (3-methoxy-phenyl) -prop-2-ynyl] -piperidine ( 3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenyl) prop) 2-ynyl] -piperidine (5R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyethyl) -4-yl) propyl] -1- [3- (thien-2-yl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl- [3- (R, S)) hydroxy-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (thien-3-yl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyqumol-4-yl) propyl] -1- [3- (thiazol-2-yl) -prop-2-ynyl] -piperidin (3R) 4R) -3-Hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazol-4-yl) propyl) 2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thiazole)] 5 (3 R, 4 R) -3-hydroxy-methyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) -5-yl) -prop-2-ynyl] -piperidine propyl] -1- [3- (oxa2ol-2-yl) -prop-2-ynyl] -piperidine 120 2 2 154 (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy) 3- (6-Methoxy-iminolin-4-yl) propyl] -1- [3- (oxazol-4-yl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl-4- [3 - (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-5-yl) -prop-2-ynyl] -piperidine (3R, 4R> 3) 4-Hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxy-quinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl-4 - [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-3-yl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (pyridin-4-yl) prop-2 -ynyl] -piperidine (3R4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrimidin-2- yl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methioxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) -prop-2-ynyl] -piperidine (3R4R) -3-hydroxymethyl-4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] ] -1- [3- (pyridazin-3-yl) -prop-2-ynyl] -piperidine (3R4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin) 4-yl) propyl] -1- [3- (pyridazin-4-yl) -prop-2-ynyl] -piperidine (3R4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro- 3- (6-Methoxyquinolin-4-yl) propyl] -1- [2-phenylthio-ethyl] piperidine (3R4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxy) -methyl) -piperidine 4-yl) propyl] -1- [3-phenylthio-propyl] piperidine (3R4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6- methoxyquinolin-4-yl) propyl] -1- [2- (2-fluorophenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (RS) -fluoro-3 '( 6-Methoxyquinolin-1-yl) propyl] -1- [3- (2-fluorophenylthio) propyl] piperidine (3R4R) -3-hyoxymethyl [3- (R, S) -fluoro-3- ( 6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluorophenylthio) ethyl] piperidine (3R4R) -3-hydroxylmethyl-4- [3- (R, S) fluoro) 3- (6-Methyloxy [uinolin -yl] propyl] -1- [3- (3-fluorophenylthio) propyl] piperidine (3R4R) -3-hydroxymethyl- [3- (R, S) -fluoro) 3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (4-fluorophenylthio) ethyl] piperidine (3R4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro) 3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl- [3- (R, S) -fluoro- 3- (6-Methoxyquinolin-yl) propyl] -1- [2- (2-chlorophenylthio) ethyl] piperidine 12022 (3R, 4R) -3-hydroxymethyl-4- [3 '(R, S)) -iluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (2-chlorophenylbio) propyl] piperidine (3R, 4R) -3-hydroxymethyl- [3- (R, S)] fluoro-3- (6-m ethoxyquinol-4-yl) propyl] -1- [2- (3-chlorophenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6- Inethoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6- Methyl (quinolin-4-yl) propyl] -1- [2- (4-chlorophenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6- methoxyquinol-4-yl) propyl] -1- [3- (4-chlorophenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6- Methoxyquinolin-4-yl) propyl] -1- [2- (2-methylphenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6- methoxyqumolin-4-yl) propyl] -1- [3- (2-methylphenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6- methoxyqumolin-4-yl) propyl] -1- [2- (3-methylphenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6 ~ methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6- meth oxyqumolin-4-yl) propyl] -1- [2- (4-methylphenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6- methoxyquinol-4-yl) propyl] -1- [3- (4-methylphenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6- methoxyqumolin-4-yl) propyl] -1- [2- (2-trifluoromethylphenylthio) butyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6- Methoxyqumol-4-yl) propyl] -1- [3- (2-trifluoromethylphenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl] -4- [3- (R, S) -fluoro-3- Methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethylphenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethylphenylthio) ethyl] piperidine Methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenylthio) propyl] piperidine Methoxyquinolin-4-yl) propyl] -1- [2- (4-trifluoromethylphenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (4-trifluoromethylphenylthio) ethyl] piperidine Methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenylthio) propyl) piperidine (3-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenylthio) propyl] piperidine R, 4R) -3-hydroxymethyl-4- [3- (R, S) -iluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2 "(2-methoxyphenylthio) ethyl] piperidine 120 2 2 156 (3R, 4R) -3-hydroxynethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methoxyphenylthio) etfayl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3 - (3-methoxyphenylthio) propyl] ] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinol-4-yl) propyl] -1 - [2- (4-methoxyphenylthio)] ) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-yl4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4- o methoxyphenylthio) piOpyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyqumolin-4-yl) propyl] -1- [2- (thien -3-yl) thioethyl] piperidin (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluon> 3- (6-methoxyquiolin-4-yl) propyl] -1- [3- (thien-3-yl) thioprop yl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyqumolin-4-yl) propyl] -1- [2- 2-yl) thioethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyqumol-4-yl) propyl] -1- [3- (2-yl) thiopropyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinol-4-yl) propyl] -1 - [2- (fur-3-yl) thioethyl] piperidin (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl)] propyl] -1- [3- (fur-3-yl) thiopropyl] piperidin (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4- yl) propyl] -1- [2- (thiazol-2-yl) thioethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinol) 4-yl) propyl] -1- [3- (thiazol-2-yl) thiopropyl] piperidine (3RtR) -3-hydroxymethylbenzyl- [3- (RtS) -fluoro-3- (6-methoxyqumolin-4- yl) propyl] -1- [2- (oxa-2-yl) thioethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxy quinolin-4-yl) propyl] -1- [3- (oxa-2-ol-2-yl) thiopropyl] piperidine (3R-4R) -3-hydroxymethyl- 4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-yl) thioethyl] piperidine (3R, 4R) -3- hydroxymethyl- 4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) thiopropyl] piperidine 3 (3R, 4R) ) -3-hydroxymethyl- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-3-yl) thioheyl] piperidine 120 22 157 (3R, 4R) -3-Hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (pyridin-3-yl) thiopropyl) ] (3R, 4R) -3-Hydro-methyl-4- [3- (R, S) -iluor (> 3- (6-methioxyquinolin-4-yl) propyl] -1-yl] pyridin 4 (yl) thioethyl] piperidine 5 (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-1-yl) propyl] -1- [3- ( pyridin-4-yl) thiopropyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluon) -3- (6-methoxyqumol-4-yl) propyl] -1- [2] [(3R, 4R) -3-Hydroxymethyl] -4- [3- (R, S) -Iluoro-3- (6-methoxyquinolin-4-yl) propyl] -1-yl] pyrimidin-2-yl) methyl] piperidin β-omega-yrimidm-2-yl) thiopropylpiperidine

(3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoK>-3-(6-métboxyqumolin-4-yl)propyl]-l-[2-(pyraziQ -2-yl)thioéthyl]pipéridme (3R,4R)-3-hydroxyméthyl^-[3-(R,S)-fluoro-3-(6-méihoxyqumolin-4-yl)propyl]-l -[3-(pyra2m-2-yl)thiopropyl]pipéri<üne 15 (3R,4R>3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-^yridazin-3-yl)thioéthyl]pipéridme (3R4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinoliii-4-yl)propyl]-l-[3- (pyridazin-3-yl)thiopropyl]pipéridin.e (3R,4R)-3-hydroxyméthyl^4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-l-[2-2 o (pyridazin-4-yl)thioéthyl]pipéridme (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolm-4-yl)propyl]-1 -[3-^yridazin-4-yl)thiopropyl]pipéridine (3R,4R)-3-hydroxyméÜiyl-4-[3-(R,S)-fiuoro-3-(6-méthoxyquinolm-4-yl)propyl]-l-[3-phéayl- prop-2-ynyl]-pipéridine 2 5 (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6~méthoxyquinolm-4-yl)propyl]-1 -[3-(2- fluoro-phényl)-prop-2-ynyl]-pipéridme (3R,4R>3-hydroxyméthyl-4-[3-<R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(3- fluorœphényl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-30 fluoro-phényl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-ch]oro-phényl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyqu.inolin-4-yl)propyl]-l-[3-(3- chloro-phényl)-prop-2-ynyl]-pipéridine 3 5 (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4- chloro-phényl)-prop-2-ynyl]-pipéridine 120 22 158 (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3-(2-méthyl-phényl)-prop-2-ynyl]-pipéridine (3R,4R>3-hydroxyméthyl^-[3-(R,S>-fluoro-3-(6-méthoxyqukiolin-4-yl)propyl]-1 -[3-(3-méthyl-phényl)-prop-2-ynyl]-pipéridme (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-méthyl-phényl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyniéthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 ~[3-(2-trifluorométhyl-phényl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-niéthoxyqumolin-4-yl)propyl]-1 -[3-(3-trifluorométhyl-phényl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyinéîhyl-4-[3-(R,S)-fluoro-3-(6-mé±oxyquinolm-4-yl)propyl]-1 -[3-(4-trifluorométhyl-phényl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -[3-(2-méthoxy-phényl)-prop-2-ynyl]-pipéridine (3R.4R)-3-hydroxyméthyl-4-[3-(R,S)-iluoro-3 -(6-mé±oxyquinolin-4-yl)propyl]-1 -[3-(3-méthoxy-phényl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyniéthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(4-méthoxy-phényl)-prop-2-ynyl]-pipéridme (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(tbien- 2- yl)-prop-2-ynyl]-pipéridine (3R-4R)-3-hydrox5Tnéthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thien- 3- yl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-mé±oxyquinolin-4-yl)propyl]-l-[3-(thiazol- 2-yl)-prop-2-ynyl]-pipéridine (3R.4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thia2ol- 4- yl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-{6-méîhox\'quinolin-4-yl)propyl]-l-[3-(thiazol- 5- vl)-prop-2-ynyl]-pipéridine (3 R,4R)-3 -hydroxyméthyl-4- [3-(R,S)-fluoro- 3-(6-méthoxyquinolin-4-yl)propyl] -1 -[3 -(oxazol-2-yl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxymé±yl-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(oxazol- 4- yl)-prop-2-ynyl]-pipéndine (3R,4R)-3-hydroxyméthyl^-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(oxazol- 5- yl)-prop-2-ynyl]-pipéridine * (3R.4R)-3-hydroxymé±yl-4-[3-(R,S)-fluoro-3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[3-(pyridin-2-yl)-prop-2-\,nyl]-pipéridine 120 22 159 (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-l-[3- (pyridiii-3-yl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méihoxyqumolin-4-yl)propyl]-l-[3- (pyridm-4-yl)-prop-2-ynyl]-pipâidiûe 5 (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-^yrimidin-2-yl)-prop-2-ynyI]-pipéridine (3R,4R)-3-hydroxyméthyl4-[3-(R)S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3- (pyrazin-2-yl)-prop-2-ynyl]-pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinoliii-4-yl)propyl]-l-[3-10 (pyridazm-3-yl)-prop-2-ynyl]-pipéridiQe (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluor(>-3-(6-nîéthoxyquinolin-4-yl)propyl]-l-[3- (pyridazin-4-yl)-prop-2-ynyl]-pipéridine(3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -Fluoro] -3- (6-metboxyquolin-4-yl) propyl] -1- [2- (pyrazol-2-yl)) thioethyl] piperidin (3R, 4R) -3-hydroxymethyl- [3- (R, S) -fluoro-3- (6-methyloxy) iminolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) ) thiopropyl] piperelene (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-yl] azin -3-yl) thioethyl] piperidin (3R4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridazine) 3-yl) thiopropyl] piperidin.e (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [ 2 - [(Pyridazin-4-yl) thioethyl] piperidin (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyqumol-4-yl) propyl] -1- [3-Yridazin-4-yl) thiopropyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [3-phenyl-prop-2-ynyl] -piperidine (5R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinol); 4-yl) propyl] -1- [3- (2-fluoro-phenyl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl- 4- [3- <R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (3-fluorenphenyl) prop-2-ynyl] -piperidine (3R, 4R) ) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4- fluoro-phenyl) prop-2) -ynyl] -piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-ch)] oro-phenyl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl ] 1- [3- (3-Chloro-phenyl) -prop-2-ynyl] -piperidine 35 (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-phenyl) -prop-2-ynyl] -piperidine 120 158 (3R, 4R) -3-hydroxymethyl-4- [3 - (R, S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (2-methyl-phenyl) -prop-2-ynyl] -piperidine (3R, 4R) -hydroxymethyl- [3- (R, S) -fluoro-3- (6-methoxyquiolin-4-yl) propyl] -1- [3- (3-methyl-phenyl) -prop-2-ynyl] -piperidin (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methyl-phenyl) - prop-2-yn yl] -piperidine (3R, 4R) -3-hydroxyniethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethyl)] phenyl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (3-Trifluoromethyl-phenyl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxy-phenyl-4- [3- (R, S) -fluoro-3- (6-methyl) - oxyquinol-4-yl) propyl] -1- [3- (4-trifluoromethyl-phenyl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S)) Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (2-methoxy-phenyl) -prop-2-ynyl] -piperidine (3R-4R) -3-hydroxymethyl-4- [3- (R, S) -Lluoro-3 - (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxy-phenyl) -prop-2-ynyl] -piperidine (3R) 4R) -3-hydroxynethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxy-phenyl) -propyl] -propionic acid; 2-ynyl] -piperidin (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (tert) 2- (2-yl) -prop-2-ynyl] -piperidine (3R-4R) -3-hydroxy-4-methyl-3- (R, S) -fluoro-3- (6-methyl) oxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) Fluoro-3- (6-methyloxyquinolin-4-yl) propyl] -1- [3- (thiazol-2-yl) prop-2-ynyl] piperidine (3R, 4R) -3-hydroxymethyl- 4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thia-2-yl) -prop-2-ynyl] -piperidine (3R) 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxy-quinolin-4-yl) propyl] -1- [3- (thiazolyl) -l) 1-Prop-2-ynyl] -piperidine (3 R, 4 R) -3-hydroxymethyl-4- [3- (R, S) -fluoro- 3- (6-methoxyquinolin-4-yl) propyl] -1- [ 3 - (oxazol-2-yl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyqumolin)] 4-yl) propyl] -1- [3- (oxazol-4-yl) -prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl- [3- (R, S) -fluoro- 3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (oxazol-5-yl) prop-2-ynyl] piperidine * (3R, 4 R) -3-hydroxymethyl-4-yl [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) prop-2-yl] -piperidine] 120 22 159 (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro 3- (6-Methoxyquolin-4-yl) propyl] -1- [3- (pyridin-3-yl) prop-2-ynyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3 - (R, S) -Fluoro-3- (6-methyloxy-iminolin-4-yl) propyl] -1- [3- (pyrid-4-yl) -prop-2-ynyl] -pipadiene (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-méthoxyqumolin-4-yl) propyl] -l- [3- ^ yrimidin-2-yl) -prop-2-ynyI ] -piperidine (3R, 4R) -3-hydroxymethyl4- [3- (R) S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl)] 1-Prop-2-ynyl] -piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3 10 (pyridaz-3-yl) -prop-2-ynyl] -piperidyl (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluorol) -3- (6-nethoxyquinolin) 4-yl) propyl] -1- [3- (pyridazin-4-yl) prop-2-ynyl] piperidine

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-fluoro-4-phénylbutyl]pipéridme-3-carboxylique 15 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l -[2-(3,5-difluorophénylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4-fluoro-4-phenylbutyl] piperidin-3-carboxylic acid acid (3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylthio) ethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3,5-difluorophénylthio)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenylthio) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl3-l-[2-(2,5-difluorophénylthio)2 o éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (2,5-difluorophenylthio) -2-ethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yî)propyl]-l-[3-(2,5-difluorophénylthio)propyl]pipéridine-3 -carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,5-difluorophenylthio) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2,3,4,6~tétrafluoro- phénylthio)éthyl]pipéridine-3-carboxylique 2 5 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 - [3-(2,3,4,6-tétrafluoro- phénylthio)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (2,3,4,6-tetrafluorophenylthio) ethyl] piperidine-3-carboxylic acid 2 (3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,3,4,6-tetrafluorophenylthio) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3-fluoro-5-chloro-phénylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (3-fluoro-5-chloro-phenylthio) ethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-fluoro-5- 3 0 chlorophénylthio)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-5-chlorophenylthio) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3-trifluorométhoxy-phénylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethoxy-phenylthio) ethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-trifluorométhoxy phénylthio)propyl]pipéridine-3-carboxylique 3 5 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l -[2-(3-cyanophénylthio) éthyl] pipéridine-3-carboxylique 160(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethoxyphenylthio) propyl] piperidine-3-carboxylic acid acid (3R, 4R) 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (3-cyanophenylthio) ethyl] piperidine-3-carboxylic acid 160

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-cyanophénylthio)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-cyanophenylthio) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyridin-2-yl)thioéthyl] pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-yl) thioethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propylj-1 -[3-(pyridin-2-yl)thiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) thiopropyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3-fluoropyridin-2-yl) thioéthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (3-fluoropyridin-2-yl) thioethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-fluoropyridin-2-yl) thiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoropyridin-2-yl) thiopropyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(cycloheptylthio)éthyl] pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (cycloheptylthio) ethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(cycloheptylthio)propyl]pipéridine-3 -carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (cycloheptylthio) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[2-(tertbutylthio)éthyl]pipéridine-3 -carboxylique(3R, 4R) -4- [3- (6-Methyl-4-yl) propyl] -1- [2- (tertbutylthio) ethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(tertbutylthio)propyl]pipéridine-3 -carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (tertbutylthio) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,3-difluoro-phényl)-prop-2 -yny l]pipéridine-3 -carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluoro-phenyl) -prop-2-yl] -piperidine-3-acid - carboxylic

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,5-difluoro-phényl)-prop-2 -yny l]pipéridine-3 -carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,5-difluoro-phenyl) -prop-2-yl] -piperidine-3-acid - carboxylic

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3,5-difluoro-phényl)-prop-2-ynyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluoro-phenyl) -prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,6-difluoro-phényl)-prop-2-ynyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluoro-phenyl) -prop-2-ynyl] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,3,5-trifluoro-phényl)-prop-2-ynyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] piperidine-3-acid carboxylic

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,3,6-trifluoro- phényl)-prop-2-ynyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,3,6-trifluorophenyl) prop-2-ynyl] piperidine-3 acid carboxylic

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-cyano-3-fluoro-phényl)-prop-2-ynyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-cyano-3-fluoro-phenyl) -prop-2-ynyl] piperidine-3-acid carboxylic

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-cyano-6-fluoro- phényl)-prop-2-ynvl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- (3-cyano-6-fluorophenyl) prop-2-ynyl) piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-acétamido-5-fluoro-phényl)-prop-2-ynyl]pipéridine-3-carboxylique 1 20 2 2 161(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2-acetamido-5-fluoro-phenyl) -prop-2-ynyl] -piperidine-3-carboxylic acid 1 20 2 2 161

Acide (3R,4R)-4-[3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-trifluorométhoxy- phényl)-prop-2-ynyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquolin-4-yl) propyl] -1- (3-trifluoromethoxyphenyl) prop-2-ynyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3- fluoro-3-phénylpropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-fluoro-3-phenylpropyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4- fluoro-4-phénylbutyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4-fluoro-4-phenylbutyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 - [3 - (3,5-difluorophénylthio)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3 - (3,5-difluorophenylthio) propyl] piperidine acid 3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2- (2,5-difluorophénylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,5-difluorophenylthio) ethyl] piperidine-acid 3-carboxylic acid

Acide (3R,4R)-4-[3-(R-S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[3- (2,5-diiluorophénylthio)propyl]pipéridme-3-carboxyiique(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (2,5-diilorophenylthio) propyl] piperidin-3- acid carboxylic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3 -(6-méthoxyquinolin-4-yl)propylJ-1 -{2- (2,3,4,6-tétrafluorophénylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3 - (6-methoxyquinolin-4-yl) propyl] -1 - {2- (2,3,4,6-tetrafluorophenylthio) ethyl acid ] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3- (2,3,4,6-tétrafluorophénylthio)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,4,6-tetrafluorophenylthio) acid) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2- (3-fluoro-5-chlorophénylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluoro-5-chlorophenylthio) ethyl] acid piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3- (3-fluoro-5-chlorophénylthio)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-5-chlorophenylthio) propyl] acid piperidine-3-carboxylic acid

Acide (3R54R)-z!-[3-(R,S)-hydroxy-3-(6-mctboxyquinolin-4-yl)propyî]-l-[2-(3R54R) -N- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl) -1- [2- (3R4R)) - [(3R4R)) - [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl) -1-

Acide (3R/P,)-4- · ?- (R.8)- hydroxy- 3-(6-3 riét')Oxyqiunolin-4-yl)propyl]-l -[3-(3 -îriflnoron nxl ioxyphényhliio)j}ropyI]5>ipcridine-3--cai'boxyliqv eAcide (3R./iR)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyi]-l-[2-(3-cyanophénylthio)éthyl]pipéridine-3-carboxylique(3R / P) -4- (R.8) -hydroxy-3- (6-hydroxyethyl) -4-yl) propyl] -1- [3- (3-fluorophenyl) oxyphenyl) amino acid ## STR2 ## (3R.ORR) -4- [3- (R) S -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -propionic acid l- [2- (3-cyanophenylthio) ethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-cyanophénylthio)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-cyanophenylthio) propyl] piperidine-3- acid carboxylic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(pyridin-2-yl)thiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) thiopropyl] piperidine acid 3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-bydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2- (3-fluoropyridin-2-yl)lhioéthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -bydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluoropyridin-2-yl) 1-yl] ethyl acid] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3- (3-fluoropyridin-2-yl)thiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoropyridin-2-yl) thiopropyl] acid piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3~(6-méthoxyquinolin-4-yl)propyl]-l-[3- (cycloheptylthio)propyl]pipéridine-3-carboxylique 12 0 2 2 162(3R, 4R) -4- [3- (R, S) -hydroxy-3 - (6-methoxyquinolin-4-yl) propyl] -1- [3- (cycloheptylthio) propyl] piperidine-3-carboxylic acid 12 0 2 2 162

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3- (tertbutylthio)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (tertbutylthio) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3- (2,3,5-trifluoro-phényl)-prop-2-ynyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) acid) -prop-2-ynyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3- (2,3,6-trifluoro-phényl)-prop-2-ynyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,6-trifluorophenyl) acid) -prop-2-ynyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-l-[3- (2-cyano-3-fluoro-phényl)-prop-2-ynyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (2-cyano-3-fluoro-phenyl) acid) -prop-2-ynyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3- cyano-6-fluoro-phényl)-prop-2-ynyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-cyano-6-fluoro-phenyl) -propanic acid 2-ynyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2- acétamido-5-fluoro-phényl)-prop-2-ynyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-acetamido-5-fluoro-phenyl) -propanic acid; 2-ynyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3- trifluorométhoxy-phényl)-prop-2-ynyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-trifluoromethoxy-phenyl) -prop-2-ynyl acid] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyI]-1 -[3- fluoro- 3 -phénylpropyl]pipéridine-3 -carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-fluoro-3-phenylpropyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4- fluoro-4-phénylbutyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [4-fluoro-4-phenylbutyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2- (3,5-difluorophénylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylthio) ethyl] piperidine-acid 3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propylj-1 -[3- (3,5-difluorophénylthio)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenylthio) propyl] piperidine-3 acid carboxylic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2- (2,5 -difluorophénylthio)éthyl]pipéridine-3 -carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,5-difluorophenylthio) ethyl] piperidine-acid 3-carboxylic

Acide (3 R,4R)-4- [3 -(R, S)-fluoro-3 -(6-méthoxyquinolin-4-yl)propyl]-1 - [3 - (2,5-difluorophénylthio)propyl]pipéridine-3-carboxylique(3 R, 4 R) -4- [3 - (R, S) -Fluoro-3 - (6-methoxyquinolin-4-yl) propyl] -1 - [3 - (2,5-difluorophenylthio) propyl] piperidine acid -3-carboxylic acid

Acide (3R,4R)-4-[3-(R.S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-1 -[2- (2.3,4,6-tétrafluorophénylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [2- (2,3,4,6-tetrafluorophenylthio) ethyl] piperidine-acid 3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propylJ-1 -[3- (2.3,4,6-tétrafluorophénylthio)propyljpipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (2,3,4,6-tetrafluorophenylthio) propyl] piperidine-3-acid carboxylic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(3- fluoro-5-chlorophénylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluoro-5-chlorophenylthio) ethyl] acid piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3- fluoro-5-chlorüphénylthio)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-5-chloro-phenylthio) propyl] acid piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(3- trifluorométhoxyphénylthio)éthyl]pipéridine-3-carboxylique 1 20 2 2 163(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethoxyphenylthio) ethyl] piperidine-3- acid carboxylic acid 1 20 2 2 163

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3- trifluorométhoxyphénylthio)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethoxyphenylthio) propyl] piperidine-3- acid carboxylic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-mé±oxyquinolin-4-yl)propyl]-1 -[2-(3- cyanophénylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-cyanophenylthio) ethyl] piperidine-acid 3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-cyanophénylthio)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-cyanophenylthio) propyl] piperidine-3- acid carboxylic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2- (pyridin-2-yl)thioéthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-yl) thioethyl] piperidine-acid 3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propylj-1 -[3- (pyridm-2-yl)thiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) thiopropyl] piperidine-3-acid carboxylic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-l-[2-(3- fluoropyridin-2-yl)thioéthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- [2- (3-fluoropyridin-2-yl) thioethyl] acid piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3- fluoropyridin-2-yl)thiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoropyridin-2-yl) thiopropyl] acid piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2- (cycloheptylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cycloheptylthio) ethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yi)propyl]-l-[3- (cycloheptylthio)propyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cycloheptylthio) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2- (tertbutylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (tertbutylthio) ethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R5S)-fîiioro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3- (tertbutyb hio)propyl]pipéridine-3 -ca rboxylique(3R, 4R) -4- [3- (R5S) -IFORO-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (tertbutylthio) propyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4- [3-(R,S) fluoro-3-(6-méthoxyquinolin-4-yl)propyi]-1 -[3- (2,3-difluoro-phényl)-prop-2-ynyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluoro-phenyl) -propyl] -acrylic acid; 2-ynyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3- (2,5-difluoro-phényl)-prop-2-ynyI]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (2,5-difluoro-phenyl) -propoic acid -2-ynyI] -piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3- (3,5-difluoro-phényl)-prop-2-ynyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluoro-phenyl) prop) acid -2-ynyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3- (2,6-difluoro-phényl)-prop-2-ynyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluoro-phenyl) prop) acid -2-ynyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3- (2,3,5-trifluoro-phényl)-prop-2-ynyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) acid) -prop-2-ynyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R.S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyI]-l-[3- (2,3,6-trifluoro-phényl)’prop-2-ynyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (2,3,6-trifluorophenyl) propanic acid -2-ynyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2- cyano-3-fluoro-phényl)-prop-2-ynyl]pipéridine-3-carboxylique 120 2 2 164(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-cyano-3-fluoro-phenyl) acid) -prop-2-ynyl] piperidine-3-carboxylic acid 120 2 2 164

Acide (3R,4R)-4-[3-(R,S)-fluorci-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3- cyano-6-flcorc-phényl)-piOp-2-ynyÎjpipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-cyano-6-flcorc-phenyl) -piO- 2-ynyÎjpipéridine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3- trifluorométhoxy-phényl)-prop-2-ynyI]pipéridine-3-carboxyiique 5 Acide (3R54R)-4-[3-(6-méthoxyquinolin-4-y])propyl]-l -[3-fluoro-3- phénylpropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-trifluoromethoxy-phenyl) prop-2-yn] acid Piperidine-3-carboxylic acid (3R54R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3-fluoro-3-phenylpropyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-fluoro-4- phénylbutyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4-fluoro-4-phenylbutyl] piperidine-3-acetic acid

Acide (3R)4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(3,5-difluoro- 1 O phény lthio)éthyl]pipéridine-3-acétique(3R) 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluoro-10-phenylthio) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3,5-difluoro- phénylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenylthio) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2.5-difluoro- phénylthio)éthyl]pipéridine-3-acétique 15 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,5-difluoro- phénylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (2,5-difluorophenylthio) ethyl] piperidine-3-acetic acid Acid (3R, 4R) 4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,5-difluorophenylthio) propyl] piperidine-3-acetic acid

Acide (3R.4R)-4-[3-(6-méthoxyquinolin-4-yl)propyi]-l-[2-(2,3}4}6-tétra- fluorophénylthio)éthyl]pipéridine-3-acétique(3R4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (2,3) 4) 6-tetrafluorophenylthio) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,3,436-tétra- 2 o fluorophénylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,3,436-tetrafluorophenylthio) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(3-fluoro-5'Chloro-phénylthio)éthyI]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (3-fluoro-5'-chloro-phenylthio) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]~ 1 -[3-(3-fluoro-5-chloro-phénylthio)propyl]pipéridine-3-acétique 25 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1-(2-(3-trifluoro- méthoxyphénylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-5-chloro-phenylthio) propyl] piperidine-3-acetic acid ( 3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (2- (3-trifluoromethoxyphenylthio) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-trifluoro- méthoxyphényIthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethoxyphenylthio) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(3-cyanophényI- 3 0 thio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (3-cyanophenylthio) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-cyanophényl-thio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-cyanophenylthio) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propÿl]-1 -[2-(pyridin-2-yl)thio- éthyl]pipéridine-3-acétique ' 35 \ 120 Z 2 165(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-yl) thioethyl] piperidine-3-acetic acid 2,165

Acide (3R,4R)-4-{3-(6-méthoxyquinolin-4-yl)propyl]“l-[3-(pyridin-2-yl)thio- propyl]pipéridine-3-acétique(3R, 4R) -4- {3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) thio-propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yi)propyl]-1 -[2-(3-fluoropyridin-2- yl)thio-éthyl3pipéridine-3-acétique 5 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yI)propyl]’l-[3-(3-fluoropyridin-2-yl)thio-propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (3-fluoropyridin-2-yl) thio-ethyl-3-piperidine-3-acetic acid acid (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] 'l- [3- (3-fluoropyridin-2-yl) thio-propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(cycioheptyl- thio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (cycloheptylthio) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(cycloheptyl- 1 O t&amp;io)propyl jpipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (cycloheptyl-10α) propyl) piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]- 1 -[2-(tertbutyl- thio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (tertbutylthio) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -(3-(tertbuty 1- thio)propyl]pipéridine-3~acétique 15 Acide (3R,4R)-4-[3-(6-méthoxyquinolm-4-yl)propyl]- l-[3-(2,3-difluoro-phényî)-prop-2-ynyl]pipéridine-3 -acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- (3- (tertbuty-1-thio) propyl] piperidine-3-acetic acid (3R, 4R) - 4- [3- (6-Methoxyquinol-4-yl) propyl] -1- [3- (2,3-difluoro-phenyl) -prop-2-ynyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yI)propyl]-1 -[3-(2,5-difluoro-phényl)- prop-2-ynyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,5-difluoro-phenyl) prop-2-ynyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -(3-(2,6-difluoro-phényl)- 2 O prop-2-ynyl]pipéridine-3 -acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- (3- (2,6-difluoro-phenyl) -2-prop-2-ynyl] piperidine-3-acid -acetic

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,3,5-trifluoro-phényl)-prop-2-ynyl]pipéridinc-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] piperidin-3-acid -acetic

Acide (3J<,4R)-4-[3-(6-méihoxyquinolin~4-yI)propyrj-l-[3-(2,3,6 trifluoro phényl)-prop-2~yijyi]pÎpéridine-3-acétique 2 5 Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]- l-[3-(2-cyano-3-fluoro- phényl)-prop-2-ynyl]pipéridine-3-acétique(3 R, 4 R) -4- [3- (6-Methyloxyquinolin-4-yl) propyl] -1- [3- (2,3,6-trifluoro-phenyl) -prop-2-yl] yl] -piperidine-3-acetic acid (3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-cyano-3-fluorophenyl) prop-2-ynyl] piperidine acid -3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-cyano-6-fluoro-phényl)-prop-2-ynyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- (3-cyano-6-fluoro-phenyl) prop-2-ynyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -(3-trifluorométhoxy- 3 0 phény l)-prop-2 -yny 1 ]p ipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- (3-trifluoromethoxy-phenyl) prop-2 -ynyl] -piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoiin-4-yl)propyl]-l-[3-fluoro- 3- phénylpropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-fluoro-3-phenylpropyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[4-fluoro- 4- phényibutyl]pipéridine-3-acétique 35 120 22 166(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [4-fluoro-4-phenylibutyl] piperidine-3-acetic acid 35 120 22 166

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(2-(3,5- difluorophénylthio)éthyl]pipéridme-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (2- (3,5-difluorophenylthio) ethyl] piperidine acid; 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(3-(3,5- difluorophénylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (3,5-difluorophenylthio) propyl] piperidine acid 3-acetic acid

Acide (3R,4R)-4-(3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1-(2-(2,5-difluorophénylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- (3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (2- (2,5-difluorophenylthio) ethyl] piperidine acid 3-acetic acid

Acide (3R,4R)-4-(3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(3-(2,5- difluorophénylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- (3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (2,5-difluorophenylthio) propyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4- [3 -(R, S)-hydroxy-3 -(6-méthoxyquinolin-4-yl)propyl]-1 - (2- (2,3,4,6-tétrafluorophénylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3 - (R, S) -hydroxy-3 - (6-methoxyquinolin-4-yl) propyl] -1- (2- (2,3,4,6-tetrafluorophenylthio) acid) ethyl] piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(3- (2,3,4,6-tétrafluorophénylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (2,3,4,6-tetrafluorophenylthio) acid) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumoliii-4-yl)propyl]-1-(2-(3- fluoro-5-chlorophénylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxy-iminol-4-yl) propyl] -1- (2- (3-fluoro-5-chlorophenylthio) ethyl] acid piperidin-3-acetic acid

Acide (3R,4R)-4-(3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(3-(3- fluoro-5 -chlorophénylthio)propyl]pipéridine-3 -acétique(3R, 4R) -4- (3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (3-fluoro-5-chlorophenylthio) propyl] acid Piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-l-[2-(3- trifluorométhoxyphénylthio)éthyl]pipéridme-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [2- (3-trifluoromethoxyphenylthio) ethyl] piperidin-3- acid acetic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(3- trifluorométhoxyphénylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (3-trifluoromethoxyphenylthio) propyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-1 -(2-(3- cyanophénylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquolin-4-yl) propyl] -1- (2- (3-cyanophenylthio) ethyl] piperidine-3- acid acetic

Acide (3 R,4R)-4- (3 -(R,S)-hydroxy-3 -(6-méthoxyquinolin-4-yl)propyl]-1-(3-(3- cyanophénylthio)propyl]pipéridine-3-acétique(3 R, 4 R) -4- (3 - (R, S) -hydroxy-3 - (6-methoxyquinolin-4-yl) propyl] -1- (3- (3-cyanophenylthio) propyl] piperidine-3-acid -acetic

Acide (3R,4R)-4-(3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2- (pyridin-2-yl)thioéthyl]pipéridine-3-acétique(3R, 4R) -4- (3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-yl) thioethyl] piperidine acid 3-acetic acid

Acide (3R,4R)-4-(3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3- (pyridin-2-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- (3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) thiopropyl] piperidine acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1-(2-(3- fluoropyridin-2-yl)thioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (2- (3-fluoropyridin-2-yl) thioethyl] acid piperidin-3-acetic acid

Acide (3R,4R)-4-(3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-(3-(3- fluoropyridin-2-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- (3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (3-fluoropyridin-2-yl) thiopropyl] acid piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2- (cycloheptylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cycloheptylthio) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyl]-l-(3-x (cycloheptylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- (3-x (cycloheptylthio) propyl] piperidine-3-acetic acid

I 120 2 2 167I 120 2 2 167

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3 -(6-méthoxyquinolin-4-yl)propyl]-1 -[2- (tertbutylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3 - (6-methoxyquinolin-4-yl) propyl] -1- [2- (tertbutylthio) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3- (tertbutylthio)propy l]pipéridine-3 -acétique 5 Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,3- difluoro-phényl)-prop-2-ynyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (tertbutylthio) propyl] piperidine-3-acetic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluoro-phenyl)) - acid prop-2-ynyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3- (2,5-difluoro-phényi)-prop-2-ynyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [3- (2,5-difluoro-phenyl) -propoic acid -2-ynyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3,5- 10 difluoro-phényl)-prop-2-ynyl]pipéridine-3 -acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluoro-phenyl) - acid prop-2-ynyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,6- difluoro-phényl)-prop-2-ynyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluoro-phenyl) prop) acid -2-ynyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyrj-l-[3-(2,3,5-trifluoro-phényl)-prop-2-ynyl]pipéridine-3-acétique 15 ' Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,3,6-trifluoro-phényl)-prop-2-ynyl]pipéridine-3 -acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl)) - prop-2-ynyl] piperidine-3-acetic acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [ 3- (2,3,6-trifluoro-phenyl) -prop-2-ynyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2-cyano-3-fluoro-phényl)-prop-2-ynyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-cyano-3-fluoro-phenyl) acid -prop-2-ynyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-cyano-6-20 fluoro-phényl)-prop-2-ynyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-cyano-6,20-fluoro-phenyl) -propoic acid -2-ynyl] piperidine-3-acetic acid

Acide (3R,4B,)-4-[3-(RJS)-hydroxy-3-(6-méthoxyquinolin-4-yl)prûpyl]-l-[3- ttifIuorcn?.é(hnxy-phényi)-prop-2-ynyI]]»i]jéridn>e-3-f;cétique(3R, 4B) -4- (3- (RJS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-tert-uoric acid (hexylphenyl) propyl) acid; 2-ynyI]] "i] jéridn> e-3-f; tetraacetic

Acide (3R5/!R)-/f-[3-(R,S)-iluoiO-3-(6“raéLlioxyqumoiin-4-yi)propyl]-l-[3-f]uoro-3- * phénylprapyl]pipéridine-3-acétique 25 Acide (3R,4R)-4-[3-(R)S)-fluoro-3-(6-méthoxyqumolin-4“yl)propyl]-l-[4-fluoro-4-phénylbutyl]pipéridine-3-acétique(3R5 / 1R) - [- [3- (R, S) -Illo] -O- (6-methyl-4-yl) propyl] -1- [3-fluoro] -3-phenyl-p-yl] -acrylic acid] piperidine-3-acetic acid (3R, 4R) -4- [3- (R) S) -fluoro-3- (6-methoxy-iminolin-4-yl) propyl] -1- [4-fluoro-4-phenylbutyl] ] piperidin-3-acetic acid

Acide (3R}4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin.-4-yl)propyl]-l-[2-(3,5- difluorophénylthio)éthyl]pipéridine-3-acétique(3 R) 4 R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylthio) ethyl] piperidine acid -3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3,5- 30 difluorophénylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenylthio) propyl] piperidine acid -3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fiuoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2,5- difluorophénylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,5-difluorophenylthio) ethyl] piperidine acid 3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yî)propyl]-l-[3-(2,5- difluorophénylthio)propyl]pipéridine-3-acétique 35 12 0 2 2 ·? 168(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,5-difluorophenylthio) propyl] piperidine acid; 3-acetic acid 35 12 0 2 2 ·? 168

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-1 -(2-(2,3,4,6-tétxafluorophénylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- (2- (2,3,4,6-tetxafluorophenylthio) acid) ethyl] piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,3,4,6-tétrafluorophénylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,4,6-tetrafluorophenylthio) acid) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-(3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(2-(3-fluoro- 5-chlorophénylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- (3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (2- (3-fluoro-5-chlorophenylthio) ethyl] acid piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-fluoro- 5-chlorophénylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-5-chlorophenylthio) propyl] acid piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1-(2-(3- trifluorométhoxyphénylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (2- (3-trifluoromethoxyphenylthio) ethyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 - [3-(3 - trifluorométhoxyphénylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethoxyphenylthio) propyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 - [2-(3 - cyanophénylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-cyanophenylthio) ethyl] piperidine-3- acid acetic

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3- cyanophénylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-cyanophenylthio) propyl] piperidine-3- acid acetic

Acide (3R,4R)-4-(3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyridin-2-yl)thioéthyl]pipéridine-3-acétique(3R, 4R) -4- (3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-yl) thioethyl] piperidine-acid 3-acetic acid

Acide (3R,4R)-4-(3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(pyridin-2 -y 1 )thiopropy l]pipéridine-3 -acétique(3R, 4R) -4- (3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) thiopropyl] acid Piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1-(2-(3- fluoropyridin-2-yl)thioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (2- (3-fluoropyridin-2-yl) thioethyl] acid piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1-(3-(3- fluoropyridin-2-yl)thiopropyl]pipéridme-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (3-fluoropyridin-2-yl) thiopropyl] acid pipéridme-3-acetic acid

Acide (3R,4R)-4-(3-(R,S)-iluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2- (cycloheptylthio)éthyI]pipéridine-3-acétique(3R, 4R) -4- (3- (R, S) -Lluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cycloheptylthio) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R.S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3- (cycloheptylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cycloheptylthio) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R.S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2- (tertbutylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (RS) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (tertbutylthio) ethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(3- (tertbutylthio)propyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (tertbutylthio) propyl] piperidine-3-acetic acid

Acide (3R,4R)-4-(3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(3-(2,3- difluoro-phényl)-prop-2-ynyl]pipéridine-3-acétique(3R, 4R) -4- (3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (2,3-difluoro-phenyl) prop) acid -2-ynyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-(3-(2,5- difluoro-phényl)-prop-2-ynyl]pipéridine-3-acétique 120 2 2 169(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (2,5-difluoro-phenyl) prop) acid -2-ynyl] piperidine-3-acetic 120 2 2 169

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3,5- difluoro-phényl)-prop-2-ynyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluoro-phenyl) prop) acid -2-ynyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(256- difluoro-phényl)-prop-2-ynyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (256-difluoro-phenyl) -prop-2) -acid ynyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl3-l-[3-(2,3,5- trifluoro-phényl)-prop-2-ynyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl)) - acid prop-2-ynyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3<6-méthoxyquinolin-4-yl)propylJ-l-[3-(2,3,6- trifluoro-phényl)-prop-2-ynyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3 (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,6-trifluorophenyl) prop) acid -2-ynyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2-cyano-3 -fluoro-phény l)-prop-2-ynyl]pip éridine-3 -acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-cyano-3-fluoro-phenyl) acid; ) -prop-2-ynyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluorot3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-cyano-6-fluoro-phényl)-prop-2-ynyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-cyano-6-fluoro-phenyl) prop-2- acid ynyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolm-4-yl)propyl]-l-[3-trifluoro-méthoxy-phényl)-prop-2-ynyl]pipéridine-3-acétique (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(3,5-difluoro- phénylthio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yI)propyl]-l-[3-(3,5-difluoro- phénylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2,5-difluoro- phénylthio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3· (6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,5-difluoro-phcnyl, ' io)propyl]pipéridine (3R,4R)-34iydiOÂy néÜiyÎ-<-[3-(6-nicihoxyq,.îinoliii-4~yl)nropyi]-î-[2-(253,4,6- télraf3uorophényllhio)cihyl]pipcrkline (3R, 4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin~4-yl)propyi]-l-[3-(2,3,4,6-tétrafluorophénylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yI)propyl]-l-[2-(3-fluoro-5- chlorophénylthio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyI-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-fluoro-5- chlorophénylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinoiin-4-yl)propyl]-l-[2-(3-trifluoro- méthoxyphénylthio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yI)propyl]-l-[3-(3-trifluoro- méthoxyphénylthio)propyl]pipéridine 120 2 2 170 (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyqumolm-4-yl)propyl3-l-[2-(3-cyano- phénylthio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolni-4-yl)propyl]-l-[3-(3-cyano- phénylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(pyridm-2-yl) thioéthyljpipéridine (3 R,4R)-3 -hydroxyméthyl-4-[3 -(6-méthoxyquinolin-4-yl)propyl] -1 -[3 -(pyridin-2-yl)thiopropyljpipéridine (3R,4R)-3 -hydroxyméthyl-4- [3 -(6-méthoxyquinolin-4-yl)propylj-1 - [2 -(3-fluoro-pyridin-2-yl)thioéthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(3-fluoro- pyridin-2-yl)thiopropyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(cyclo- heptylthio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(cyclo- heptylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3 -(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(tertbutyl-thio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(tertbutyl- thio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,3-difluoro- phényl)-prop-2-ynyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,5-difluoro- phényl)-prop-2-ynyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3,5-difluoro- phényl)-prop-2-ynyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(3-(2,6-difluoro-phényl)-prop-2-ynyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(3-(2,3,5-trifluoro-phényl)-prop-2-ynyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-(3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,3,6- trifluoro-phényl)-prop-2-ynyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquiriolin-4-yl)propyl]-l-(3-(2-cyano-3- fluoro-phényl)-prop-2-ynyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(3-cyano-6- fluoro-phényl)-prop-2-ynyl]pipéridine 171 120 22 (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-cyano-6- fluoro-phényl)-prop-2-ynyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3 - trifluorométhoxy-phényl)-pfop-2-ynyl)pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-rnéthoxyquinoIin-4-yl)propyl]-l- [2-(3,5-difluorophénylthio)éthyljpipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l- [3-(3,5-difluorophénylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l- [2-(2,5-difluorophénylthio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l- [3-(2,5-difluorophénylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2,3,4,6-tétrafluorophénylthio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méihoxyqumolin-4-yl)propyl]-l-[3-(2,3,4,6-tétrafluorophénylthio)propylJpjpéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin~4-yl)propyl]-l- [2-(3-fluoro-5-chlorophénylthio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoIin-4-yl)propy]]-l- [3-(3-fluoro-5-chlorophénylthio)propyl]pipéridine (3R,4R)-3-hydroxymcthyl-4-[3-(RJS)-hydroxy-3-(6-méthoxyqumolin-4~yl)propyl]-l- [2-(3-'trifîuojO.nié4hoxyphényîthio)éihyl]pipéridine (3R,4R)~3-hydroxymé{hyM-[3(R,S)-hydroxy-3~(6~ni6ihoxyquinolin4-yI)piOpyl]~l- [3-(3*Îiilluoroméihoxypkô(iylthio)piOpyl]pjpéridine (3R,4k)~3-hydroxyméthyî-4-[3-(RsS)-hydroxy-3-(6-rûéihoxyquinolin-4-yl)propyl]-l- [2-(3-cyanophénylthio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyI-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin.-4-yl)propyl]-l- [3-(3-cyanophényIthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l- [2-(pyridin-2-yl)thioéthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyI]-l- [3-(pyridin-2-yl)thiopropyî]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l- [2-(3-fluoropyridin-2-yl)thioéthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l- [3-(3-fluoropyridin-2-yl)thiopropyl]pipéridine 120 2 2 172 (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l- [2-(cycloheptylthio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l- [3-(cycloheptylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l- [2-(tertbutylthio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(RsS)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l- [3-(tertbutylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R.S)'hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,3-difluoro-phény l)-prop-2-ynyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3 -(2,5 -difluoro-phény l)-prop-2 -yny l]p ipéridine (3R,4R)-3-hydroxyméthyI-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3,5-difluoro-phényl)-prop-2-ynyl]p ipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l- [3-(2,6-difluoro-phényI)-prop-2-ynyl]pipéridi:ie (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3 (6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,3,5-trifluoro-phényl)-prop-2-ynyl]pipéridine (3R,4R)-3-hydroxyméthyi-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l- [3-(2,3,6-trifluoro-phényl)-prop-2-ynyl]pipéridine (3 R,4R)-3 -hydroxyméthyl-4-[3 -(R,S)-hydroxy-3-(6-méthoxyquino lin-4-y l)propylj -1 -[3-(2-cyano-3-fluoro-phényl)-prop-2-ynyl]pipéridine (3R,4R)-3-hydroxyméthyÎ-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l- [3-cyano-6-fluoro-phényl)-prop-2-ynyl]pipéridine (3R,4R)-3-hydroxyméthyI-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoîin-4-yl)propyl]-l- [3-trifluorométhoxy-phényl)-prop-2-ynyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-l-[2- (3,5-difluorophénylthio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyi-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yi)propyl]-l-[3- (3,5-difluorophénylthio)propyl]pipéridine (3R,4R)-3-hydroxyraéthyl-4-[3-(R,S)-fluoro-3-(6-méÎhoxyquinolin-4-yl)propyl]-l-[2- (2,5-difluorophénylthio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquino!in-4-yl)propyl]-l-[3- * (2,5-difluorophénylthio)propyl]pipéridine ’(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinol-4-yl) propyl] -1- (3-trifluoromethoxyphenyl) prop-2- acid ynyl] piperidine-3-acetic acid (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenylthio) propyl] piperidine (3R, 4R) 3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,5-difluorophenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4 [3 · (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,5-difluoro-phenyl, 10-propyl] piperidine (3R, 4R) -34Hydioyl] -3- (6-aminooxy, 4-iminol-4-yl) n-butyl] -I- [2- (253,4,6-trifluorophenylthio) cihyl] pipcrkline (3R, 4R) -3-hydroxymethyl-4- [3- (6- Methoxyquinolin-4-yl) propyl] -1- [3- (2,3,4,6-tetrafluorophenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4- Y1) propyl] -1- [2- (3-fluoro-5-chlorophenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methox yquinolin-4-yl) propyl] -1- [3- (3-fluoro-5-chlorophenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethoxyphenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-Trifluoromethoxyphenylthio) propyl] piperidine 120 2 170 (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyqumol-4-yl) propyl] -1- [2- (3-cyano)] phenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinol-4-yl) propyl] -1- [3- (3-cyano-phenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3 - (6-methoxyquinolin-4-yl) propyl] -1- [3 - (pyridin-2-yl) thiopropyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3 - (6-methoxyquinolin-4- yl) propyl] -1- [2- (3-fluoro-pyridin-2-yl) thioethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquolin-4-yl) propyl] - 1- [3- (3-fluoropyridin-2-yl) thiopropyl] piperidine (3 R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cycloheptylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4 [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cycloheptylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3 - (6-methoxyquinolin-4) -yl) propyl] -1- [2- (tert-butylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3-yl] propyl] -1- [2- (tert-butylthio) ethyl] piperidine - (tertbutylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl)) 1-Prop-2-ynyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,5-difluorophenyl)] - prop-2-ynyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenyl) prop) 2-ynyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (2,6-difluoro-phenyl) propylene] 2-ynyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (2,3,5-trifluorophenyl) prop) -2-ynyl] piperidine (3R, 4R) -3-hydroxymethyl-4- (3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,6-trifluorophenyl) prop-2-ynyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquirolin-4-yl) propyl] -1- (3- (2-cyano-3-fluoro-phenyl) -prop-2-ynyl) ] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (3-cyano-6-fluoro-phenyl) -prop-2-ynyl] piperidine (R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (3-cyano-6-fluoro-phenyl) prop-2-ynyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (3-trifluoromethoxy-phenyl) -pfop-2-ynyl) piperidine (3R, 4R) 3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylthio) ethyl] piperidine (3R, 4R) 3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,5-difluorophenylthio) ethyl] piperidine ( 3R, 4 R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,5-difluorophenylthio) propyl] piperidine ( 3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -l- [2- (2,3,4,6- tetrafluorophenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methyloxy-iminolin-4-yl) propyl] -1- [3- (2) 3,4,6-tetrafluorophenylthio) propyl] pyridine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2] - (3Rluoro-5-chlorophenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) prop]]] 1- [3- (3-Fluoro-5-chlorophenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (RJS) -hydroxy-3- (6-methoxyqumolin-4-yl) propyl] -1- [2- (3-trifluoro (4-yloxyphenylthio) hexyl] piperidine (3R, 4R) -3-hydroxymethyl {M- [3 (R, S) -hydroxy-3 - (6-naphthylquinolinyl) -I) pOpyl] -1- [3- (3'-trifluoromethyl) bipyronylthio) propyl] piperidine (3R, 4k) -3-hydroxymethyl-4- [3- (RsS) -hydroxy-3- (6-rifheoxyquin olin-4-yl) propyl] -1- [2- (3-cyanophenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6- methoxyquinolin-4-yl) propyl] -1- [3- (3-cyanophenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3 (6 Methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-yl) thioethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) thiopropyl) piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy) 3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (3-fluoropyridin-2-yl) thioethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) ) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoropyridin-2-yl) thiopropyl] piperidine 120 2 2 172 (3R, 4R) -3-hydroxymethyl-4 [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cycloheptylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [ 3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cycloheptylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-met Hoxyquinolin-4-yl) propyl] -1- [2- (tertbutylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (RsS) -hydroxy-3- (6-methoxyquinolin-4- yl) propyl] -1- [3- (tertbutylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (RS) 'hydroxy-3- (6-methoxyquinolin-4-yl) propyl] 1- [3- (2,3-Difluoro-phenyl) -prop-2-ynyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- ( 6-methoxyquinolin-4-yl) propyl] -1- [3- (2,5-difluoro-phenyl) -prop-2-yl] -piperidine (3R, 4R) -3-hydroxymethyl-4-yl - (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluoro-phenyl) -prop-2-ynyl] -piperidine (3R, 4R) ) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluoro-phenyl) propylene] 2-ynyl] piperidin: ie (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3 (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-ynyl) piperidin) 3,5-trifluoro-phenyl) -prop-2-ynyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) ) propyl] -1- [3- (2,3,6-trifluorophenyl) prop-2-ynyl] piperidine (3 R, 4R) -3 -hydroxymethyl-4- [3 - (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-cyano-3-fluoro-phenyl) prop-2 -ynyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-cyano-6- fluoro-phenyl) -prop-2-ynyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinin-4-yl) propyl] -1 [3-Trifluoromethoxy-phenyl] -prop-2-ynyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyqumolin-4-yl)] propyl] -1- [2- (3,5-difluorophenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4- yi) propyl] -1- [3- (3,5-difluorophenylthio) propyl] piperidine (3R, 4R) -3-hydroxyraethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinoline) 4-yl) propyl] -1- [2- (2,5-difluorophenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6- (4-yl) propyl] -1- [2- (2,5-difluorophenylthio) ethyl] piperidine methoxyquinino-4-yl) propyl] -1- [3- (2,5-difluorophenylthio) propyl] piperidine '

173 (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l- [2-(2,3,4,6-tétiafluorophénylthio)éthyl]pipéridme (3R,4R)-3 -hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(2,3,4,6-tétrafluorophénylthio)propyl]pipéridine - 5 (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 - [2-(3-fluoro-5-chlorophénylthio)éthyl]pipéridme (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l- [3-(3-fluoro-5-chlorophénylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propylj-l-îo [2-(3-trifluorométhoxyphénylthio)éthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l- [3-(3-trifluorométhoxyphénylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l- [2-(3-cyanophénylthio)éthyl]pipéridine 15 (3R,4R)-3«hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propylJ-1 -[3-(3-cyanophénylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-l- [2-(pyridin-2-yl)thioéthyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-iïiéthoxyquinolin-4-yl)propyl]-l-2 0 [3-(pyridin-2-yl)thiopropyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-flnoro-3-(6-méthoxyquinoIin-4-yî)propyl]-l-[2-(3 -fiuoropyridin-2-yl)tbioéthy] jpipéri dîne (3 R, 4R)-3-hydroxyiriétby]-4~[3 -(R,S)-fluoro-3- (6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-fluoropyridin-2-yl)lhiopropyl]pipéridine 2 5 (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 - [2-(cycloheptylthio)éth.yl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3 -(cycloheptylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-30 [2-(tertbutyIthio)éthylJpipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yi)propyl]-l-[3 -(tertbutylthio)propyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l- [3-(2,3-difluoro-phényl)-prop-2-ynyl]pipéridine 3 5 (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 - [3-(2,5-difluoro-phényl)-prop-2-ynyl]pipéridine 120 2 2 174 (3R54R)-3-hydroxyméthyI-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yi)propyl]-l-[3- (3,5-difluoro-phényl)-prop-2-ynyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3- (2,6-difluoro-phényl)-prop-2-ynyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3- (2,3,5-trifluoro-phényl)-prop-2-ynyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propylJ-l-[3- (2,3,6-trifluoro-phényl)-prop-2-ynyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-{3-(R5S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3- (2-cyano-3-fluoro-phényl)-prop-2-ynyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3- cyano-6-fluoro-phényl)-prop-2-ynyl]pipéridine (3R,4R)-3-hydroxyméthyl-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3- trifluorométhoxy-phényl)-prop-2-ynyl]pipéridine173 (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,4, 6-Tetrafluorophenylthio) ethyl] piperidin (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- ( 2,3,4,6-tetrafluorophenylthio) propyl] piperidine-5 (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl) 1 - [2- (3-fluoro-5-chlorophenylthio) ethyl] piperidin (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4)] 1H-propyl] -1- [3- (3-fluoro-5-chlorophenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3 - Methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethoxyphenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethoxyphenylthio) ethyl] piperidine Methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethoxyphenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethoxyphenylthio) propyl] piperidine Methoxyquinolin-4-yl) propyl] -1- [2- (3-cyanophenylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- ( 6-metho xyquinolin-4-yl) propyl] -1- [3- (3-cyanophenylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyqumolin) 4-yl) propyl] -1- [2- (pyridin-2-yl) thioethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-yl) propyl] -1- [2- (pyridin-2-yl) thioethyl] piperidine 1H-Ethoxyquinolin-4-yl) propyl] -1- [3- (pyridin-2-yl) thiopropyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -flnoro- 3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (3-fluoropyridin-2-yl) butyl] piperinde (3 R, 4 R) -3-hydroxyrietyl] -4- [3 - ( R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoropyridin-2-yl) 1-i-propyl] piperidine (3R, 4R) -3-hydroxymethyl- 4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cycloheptylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl- 4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (cycloheptylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (tertbutylthio) ethyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-m thoxyquinolin-4-yl) propyl] -1- [3- (tertbutylthio) propyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin) 4-yl) propyl] -1- [3- (2,3-difluoro-phenyl) -prop-2-ynyl] piperidine 3 (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) ) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,5-difluoro-phenyl) -prop-2-ynyl] piperidine 120 2 174 (3R54R) -3- hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluoro-phenyl) prop-2-ynyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluoro- phenyl) -prop-2-ynyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [ 3- (2,3,5-Trifluoro-phenyl) -prop-2-ynyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin) 4-yl) propyl] -1- [3- (2,3,6-trifluoro-phenyl) -prop-2-ynyl] piperidine (3R, 4R) -3-hydroxymethyl-4- {3- (R5S) - Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-cyano-3-fluoro-phenyl) prop-2-ynyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-cyano-6-fluoro-phenyl] ) -prop-2-ynyl] piperidine (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3] - trifluoromethoxy-phenyl) -prop-2-ynyl] piperidine

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(6-fluoropyridin-2- yl)thioéthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (6-fluoropyridin-2-yl) thioethyl] piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(6-fluoropyridin-2- yl)thiopropyl]pipéridme-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (6-fluoropyridin-2-yl) thiopropyl] piperidin-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(6- fluoropyridin-2-yl)thioéthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (6-fluoropyridin-2-yl) thioethyl] acid piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(6- fluoropyridin-2-yl)thiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (6-fluoropyridin-2-yl) thiopropyl] acid piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(6- fluoropyridin-2-yl)thioéthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (6-fluoropyridin-2-yl) thioethyl] acid piperidine-3-carboxylic acid

Acide (3R,4R)-4-[3-(R5S)-fluoro-3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(6- fluoropyridin-2-yl)thiopropyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R5S) -Fluoro-3- (6-methoxyquolin-4-yl) propyl] -1- [3- (6-fluoropyridin-2-yl) thiopropyl] piperidine-acid 3-carboxylic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(6-fluoropyridin-2- yl)thioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (6-fluoropyridin-2-yl) thioethyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yi)propyl]-l-[3-(6-fluoropyridm-2- yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (6-fluoropyrid-2-yl) thiopropyl] piperidine-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyI]-1 -[2-(6- fluoropyridin-2-yl)thioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquolin-4-yl) propyl] -1- [2- (6-fluoropyridin-2-yl) thioethyl] acid piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R.S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(6- fluoropyridiia-2-yl)thiopropyl]pipéridine-3-acétique 12 0 2 2 175(3R, 4R) -4- [3- (RS) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (6-fluoropyridi-2-yl) thiopropyl] piperidine acid 3-acetic acid 12 0 2 2 175

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 - [2-(6 - fhioropyridin-2-yl)thioéthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (6-chloropyridin-2-yl) thioethyl] acid piperidin-3-acetic acid

Acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(6- fluoropyridin-2-yl)thiopropyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (6-fluoropyridin-2-yl) thiopropyl] acid piperidin-3-acetic acid

Les exemples suivants donnés à titre non limitatif illustrent la présente invention.The following examples given by way of non-limiting example illustrate the present invention.

Exemple 2Example 2

Dichlorhydrate de l’acide (3R,4R)-4-[3-(6-méthoxyquÎnolin-4.-yI)propyl]-l-{3-(thién-2-yl)prop-2-ynyl)]pipéridine-3-carboxylique A une solution de 0,185 g d’acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(prop-2-ynyl)pipéridine-3-carboxylique dans 4 cm3 de diméthylforriiamide anhydre,on ajoute sous agitation 0,057 cm3 de 2-iodothiophène et 1,42 cm3 de triéthylamine,puis 0,038 g de tétrakis (triphénylphosphine) palladium et 0,019 g d’iodure cuivreux.La solution est agitée pendant 20 heures à une température voisine de 20°C. 75 cm3d’acétate d’éthyle et 75 cm3 d’eau sont ajoutés au mélange réactionnel. Aprèsagitation du mélange, la phase aqueuse est décantée, puis neutralisée à pH 6 paraddition d’une solution aqueuse d’acide chlorhydrique 0,lN. La phase aqueuse estextraite par 50 cm3 d’acétate d’éthyle ; l’extrait est lavé par 2 fois 75 cm3 d’unesolution aqueuse saturée de chlorure de sodium. La solution organique est séchée sursulfate de magnésium, filtrée, puis mélangée sous pression réduite (5 LP a), à unetempérature voisine de 4Ü°C. On obtient 0,090 g d’une huile de couleur jaune quel’on pimLe par chromatographie sur une colonne de gel de silice.(granulométrie 20-45 μ ; diamètre 1 cm ; hauteur 30 cm), en éluant, sous une pression de 50 kPa d’azote,par un mélange dichlorométhane-méthanol (92/8 en volumes), et en recueillant desfractions de 50 cm3. Les fractions 12 à 15 sont réunies, concentrées sous pressionréduite (5 kPa), à une température voisine de 40°C. L’huile obtenue est reprise par1 cm3 de dioxanne chlorhydrique 4N. Après concentration dans les mêmes conditionsque précédemment, et reprise du résidu dans 10 cm3 d’éther diéthylique, on recueilleaprès filtration, 0,030 g de dichlorhydrate d’acide (3R,4R)-4-[3-(6-méthoxyquinolin- 4-yl)propyl]-1-[3-/thién-2-yl)prop-2-ynyl)]pipéridine-3-carboxylique, sous formed’un solide blanc.(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- (3- (thien-2-yl) prop-2-ynyl)] piperidine acid dihydrochloride 3-carboxylic acid To a solution of 0.185 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-carboxylic acid in 4 cm3 of anhydrous dimethylformamide are added, with stirring, 0.057 cm3 of 2-iodothiophene and 1.42 cm3 of triethylamine are added, followed by 0.038 g of tetrakis (triphenylphosphine) palladium and 0.019 g of cuprous iodide.The solution is stirred for 20 hours at a temperature of temperature around 20 ° C. 75 cm3 of ethyl acetate and 75 cm3 of water are added to the reaction mixture. After stirring the mixture, the aqueous phase is decanted and then neutralized to pH 6 paraddition of an aqueous solution of 0.1N hydrochloric acid. The aqueous phase is extracted with 50 cm3 of ethyl acetate; the extract is washed with twice 75 cm3 of a saturated aqueous solution of sodium chloride. The organic solution is dried over magnesium sulphate, filtered and then mixed under reduced pressure (5 μL) at a temperature of about 40 ° C. 0.090 g of a yellow oil, which is obtained by chromatography on a column of silica gel (particle size 20-45 μ, diameter 1 cm, height 30 cm), eluting under a pressure of 50 kPa, are obtained. of nitrogen, with a dichloromethane-methanol mixture (92/8 by volume), and collecting fractions of 50 cm3. Fractions 12 to 15 are combined and concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. The oil obtained is taken up in 1 cm3 of 4N hydrochloric dioxane. After concentration under the same conditions as above, and the residue is taken up in 10 cm3 of diethyl ether, 0.030 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) dihydrochloride are collected after filtration. ) propyl] -1- [3- [thien-2-yl] prop-2-ynyl)] piperidine-3-carboxylic acid as a white solid.

Spectre de R.M.N. (400 MHz, (CD3)2SO d6, δ en ppm) : de 1,15 à 2,10 et de 3,00à 3,65 (mts : 14H) ; 3,98 (s : 3H) ; de 4,25 à 4,55 (mf : 2H) ; 7,16 (dd, J = 5 et 3 Hz : 120 2 2 176 •il ’t 1H) ; de 7,40 à 7,60 (mt : 4H) ; 7,75 (d large, J = 5 Hz : 1H) ; 7,96 (mt : 1H) ; 8,79(mt : 1H) ; de 10,50 à 10,70 (mf étalé : 1H) ; de 12,85 à 13,15 (mf étalé : 1H). L’acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(prop-2-ynyl)pipéridine-3-carboxylique peut être préparé de la manière suivante : 5 0,3 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(prop-2-ynyl)pipéridine-3- carboxylate de (prop-2-ynyle) dans 3 cm3 de dioxanne et 1,48 cm3 de soude N sontchauffés, sous agitation, à une température voisine de 70°C pendant 17 heures. Lemélange réactionnel est concentré sous pression réduite (5 kPa), à une températurevoisine de 50°C. Au résidu solide obtenu, on ajoute 1,48 cm3 d’acide chlorhydrique 10 aqueux normal, puis 10 cm3 d’eau. La solution obtenue est extraite par 5 fois 20 cm3de dichlorométhane. Les extraits organiques sont réunis, puis concentrés souspression réduite (5 kPa). On obtient 0,189 g d’acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -(prop-2-ynyl)pipéridine-3-carboxylique, sous formed’une meringue de couleur blanche. 15 Le (3R,4R)-4-[3-(6-methoxyquinolin-4-yl)propyl]-l-(prop-2-ynyI)pipéridine-3-carboxylate de -prop-2-ynyle peut être préparé de la manière suivante : A une solution de 0,835 g de chlorhydrate d’acide (3R,4R)-4-[3-(6-méthoxyquinolin- 4-yl)propyl]pipéridine-3-carboxylique, dans 15 cm3 de diméthylformamide anhydre,on ajoute 0,95 g de carbonate de potassium, puis 0,36 cm3 de bromure de propargyle. 20 Le mélange est agité sous atmosphère d’azote, à une température voisine de 70°Cpendant 18 heures. On ajoute au mélange réactionnel 100 cm3 d’acétate d’éthyle et100 cm3 d’eau distillée. La phase organique est décantée, puis lavée par 5 fois 40 cm3d’eau, et 2 fois 50 cm3 d’une solution saturée de chlorure de sodium. La solutionorganique est séchée sur sulfate de magnésium, filtrée, puis mélangée sous pression 25 réduite (5 kPa), à une température voisine de 40°C, jusqu'à concentration maximum.L’huile obtenue est purifiée par chromatographie sur une colonne de gel de silice(granulométrie 20-45 μ ; diamètre 2 cm ; hauteur 40 cm), en éluant, sous une pressiond’azote de 50 kPa, par de l’acétate d’éthyle, et en recueillant des fractions de 50 cm3.Les fractions 17 à 21 sont réunies, concentrées sous pression réduite (5 kPa), à une 30 température de 40°C. On obtient 0,300 g de (3R,4R)-4-[3-(6-methoxyquinolin-4-yl)propyl]-l-(prop-2-ynyl)-3-pipéridinecarboxylate de prop-2-ynyle, sous formed’une huile de couleur jaune. tSpectrum of R.M.N. (400 MHz, (CD3) 2SO d6, δ in ppm): from 1.15 to 2.10 and from 3.00 to 3.65 (mts: 14H); 3.98 (s: 3H); from 4.25 to 4.55 (mf: 2H); 7.16 (dd, J = 5 and 3 Hz: 120); from 7.40 to 7.60 (mt: 4H); 7.75 (broad d, J = 5 Hz: 1H); 7.96 (mt: 1H); 8.79 (mt: 1H); from 10.50 to 10.70 (mf spread: 1H); from 12.85 to 13.15 (mf spread: 1H). (3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-carboxylic acid can be prepared in the following manner: , 3 g of (3-propyl) -1- (prop-2-ynyl) piperidine-3-carboxylate (2-propyl) -propyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1-carboxylate in 3 cm3 of dioxane and 1.48 cm3 of N sodium hydroxide are heated, with stirring, at a temperature of 70 ° C for 17 hours. The reaction mixture is concentrated under reduced pressure (5 kPa) at a temperature of about 50 ° C. To the solid residue obtained, 1.48 cm 3 of normal aqueous hydrochloric acid and then 10 cm 3 of water are added. The solution obtained is extracted with 5 times 20 cm3 of dichloromethane. The organic extracts are combined and then concentrated under reduced pressure (5 kPa). 0.189 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-carboxylic acid, as a meringue, are obtained. white color. (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-carboxylic acid-propyl-2-yl can be prepared from the following procedure: To a solution of 0.835 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylic acid hydrochloride in 15 cm3 of anhydrous dimethylformamide, 0.95 g of potassium carbonate and then 0.36 cm3 of propargyl bromide are added. The mixture is stirred under a nitrogen atmosphere at a temperature in the region of 70 ° C. for 18 hours. 100 cm3 of ethyl acetate and 100 cm3 of distilled water are added to the reaction mixture. The organic phase is decanted, then washed with 5 times 40 cm3 of water, and 2 times 50 cm3 of a saturated solution of sodium chloride. The organic solution is dried over magnesium sulphate, filtered and then mixed under reduced pressure (5 kPa), at a temperature in the region of 40 ° C., to a maximum concentration. The oil obtained is purified by chromatography on a gel column. of silica (particle size 20-45 μ, diameter 2 cm, height 40 cm), eluting under a nitrogen pressure of 50 kPa, with ethyl acetate, and collecting fractions of 50 cm 3. 17 to 21 are combined, concentrated under reduced pressure (5 kPa), at a temperature of 40 ° C. 0.300 g of prop-2-ynyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) -3-piperidinecarboxylate are obtained, in the form of a yellow oil. t

Le chlorhydrate de l’acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-carboxylique peut être préparé de la manière suivante : 12 0 2 2 177 8,8 g de d’acide (3R,4R)-l-benzoyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-carboxylique sont chauffés, sous agitation, dans 200 cm3 d’acide chlorhydriqueaqueux 5N, à une température voisine de 100°C pendant 48 heures. Le mélangeréactionnel est concentré sous pression réduite (5 kPa) à une température voisine de 5 50°C. Le résidu est repris par 100 cm3 d’acétone. Le mélange est concentré sous pression réduite (5 kPa), à une température voisine de 60°C. Cette opération estrépétée deux fois supplémentaires. Le résidu est enfin trituré dans 100 cm3 d’acétone,jusqu'à cristallisation. Après filtration des cristaux, et séchage au dessicateur souspression réduite (10 kPa), on obtient 7,2 g de chlorhydrate d’acide (3R,4R)-4-[3-(6- 10 méthoxyquinolin-4-yl)propyl]pipéridine-3-carboxylique, sous forme d’un solide beigefondant aux environs de 270°C (fusion pâteuse). L’acide (3R,4R)-1 -benzoyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-carboxylique peut être préparé de la manière suivante : 25 g de (3R,4R)-l-benzoyl--4-[3-(6-méthoxyquinolin-4-yl)propyl]-3-vinyl pipéridine15 sont dissous dans un mélange de 250 cm3 de tétrachlorure de carbone et 250 cm3d’acétonitrile. 51,3 g de métapériodate de sodium en solution dans 325 cm3 d’eau sontajoutés à une température voisine de 20°C, sous bonne agitation, puis 0,27 g detrichlorure de ruthénium hydrate. La réaction, légèrement exothermique, estmaintenue au voisinage de 30°C pendant 15 minutes après l’addition des réactifs. Le 20 mélange est agité 2 heures à température ambiante. La suspension obtenue est filtrée,l’insoluble lavé par 5 fois 80 cm3 de dichlorométbane. Après agitation du filtrat, laphase organique est décantée, la phase aqueuse saturée par du chlorure de sodium,puis extraite par deux portions supplémentaires de 300 cm3 de dichlorométhane. Lesextraits organiques réunis sont lavés à l’eau (3 fois 200 cm3), séchés sur sulfate de 25 magnésium, filtrés sur papier, puis concentrés sous pression réduite (5 kPa), à unetempérature voisine de 40°C. On obtient 23,2 g d’une huile que l’on purifie parchromatographie, à pression atmosphérique, sur gel de silice (granulométrie 20-45 μ ;diamètre 6,5 cm ; hauteur 30 cm), en éluant par un mélange de dichlorométhane-méthanol (97/3 en volumes), et en recueillant des fractions de 400 cm3. Les fractions 30 4 à 8 sont réunies, puis concentrées sous pression réduite (5 kPa). On obtient 11,8 g d’une huile brune. Celle-ci est dissoute dans 60 cm3 d’acétonitrile portés au refluxpendant quelques minutes en présence de 0,5 g de charbon animal. Après filtration, lasolution obtenue est refroidie. Le produit qui a cristallisé est essoré, lavé par 2 fois10 cm3 d’acétonitrile. Le solide est séché au dessiccateur sous vide potassique 120 2 2 178 (lOkPa). On obtient 8,8 g d’acide (3R,4R)-l-benzoyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-carboxylique sous forme d’un solide beige fondant à 160°C.(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] piperidine-3-carboxylic acid hydrochloride can be prepared in the following manner: 12 0 2 2 177 8.8 g (3R, 4R) -1-Benzoyl-4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylic acid are heated, with stirring, in 200 cm 3 of 5N hydrochloric acid, at a temperature of about 100 ° C for 48 hours. The reaction mixture is concentrated under reduced pressure (5 kPa) at a temperature in the region of 50.degree. The residue is taken up in 100 cm3 of acetone. The mixture is concentrated under reduced pressure (5 kPa) at a temperature in the region of 60 ° C. This operation is repeated twice more. The residue is finally triturated in 100 cm3 of acetone, until crystallization. After filtration of the crystals and drying under reduced pressure (10 kPa), 7.2 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] hydrochloride are obtained. piperidine-3-carboxylic acid, in the form of a beige solid melting at about 270 ° C (pasty melting). (3R, 4R) -1-Benzoyl-4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylic acid can be prepared in the following manner: 25 g of (3R, 4R) 1-Benzoyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -3-vinylpiperidine are dissolved in a mixture of 250 cc of carbon tetrachloride and 250 cc of acetonitrile. 51.3 g of sodium metaperiodate in solution in 325 cm3 of water are added at a temperature of 20 ° C, with good stirring, then 0.27 g of ruthenium hydrofluoride hydrate. The reaction, slightly exothermic, is maintained near 30 ° C for 15 minutes after the addition of reagents. The mixture is stirred for 2 hours at room temperature. The suspension obtained is filtered and the insoluble material is washed with 5 times 80 cm 3 of dichloromethane. After stirring the filtrate, the organic phase is decanted, the aqueous phase saturated with sodium chloride and extracted with two additional portions of 300 cm3 of dichloromethane. The combined organic extracts are washed with water (3 × 200 cm 3), dried over magnesium sulphate, filtered on paper and then concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 23.2 g of an oil which is purified by chromatography, at atmospheric pressure, on silica gel (particle size 20-45 μ, diameter 6.5 cm, height 30 cm), eluting with a mixture of dichloromethane -methanol (97/3 by volume), and collecting fractions of 400 cm3. Fractions 4 to 8 are combined and then concentrated under reduced pressure (5 kPa). 11.8 g of a brown oil are obtained. This is dissolved in 60 cm3 of acetonitrile refluxed for a few minutes in the presence of 0.5 g of animal charcoal. After filtration, the resulting solution is cooled. The product which has crystallized is drained and washed twice with 10 cm3 of acetonitrile. The solid is dried in a desiccator under potassium vacuum 120 2 2 178 (10 kPa). 8.8 g of (3R, 4R) -1-benzoyl-4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylic acid are obtained in the form of a beige solid, melting at 160 ° C. ° C.

La (3R,4R)-1 -benzoyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-3-vinylpipéridine peutêtre préparée de la manière suivante : A une solution agitée de 20,8 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-3-vinylpipéridine dans 270 cm3 de chloroforme, on ajoute 18,4 cm3 de triéthylamine,puis, en 1 heure, une solution de 7,2 cm3 de chlorure de benzoyle dans 50 cm3 dechloroforme. Après 1 heure 30 minutes d’agitation du mélange à une températurevoisine de 20°C, 100 cm3 d’eau distillée sont ajoutés au mélange réactionnel. Laphase chloroformique est décantée, lavée par 2 fois 100 cm3 d’eau, puis séchée sursulfate de magnésium. Après filtration sur papier, la solution chloroformique estconcentrée sous pression réduite (5 kPa), à une température voisine de 40°C. Onobtient 25 g de (3R,4R)-l-benzoyl-4-[3-(6-méthoxyquinolin-4-yl)propyl]-3-vinylpipéridine, sous forme d’huile brune.(3R, 4R) -1-Benzoyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -3-vinylpiperidine can be prepared as follows: To a stirred solution of 20.8 g of (3R) , 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -3-vinylpiperidine in 270 cm3 of chloroform, 18.4 cm3 of triethylamine are added, then, in 1 hour, a solution of 7, 2 cm3 of benzoyl chloride in 50 cm3 of chloroform. After 1 hour 30 minutes of stirring the mixture at a temperature of 20 ° C, 100 cm3 of distilled water are added to the reaction mixture. Chloroformic Laphase is decanted, washed with 2 times 100 cm3 of water and then dried over magnesium sulfate. After filtration on paper, the chloroform solution is concentrated under reduced pressure (5 kPa) at a temperature of 40 ° C. 25 g of (3R, 4R) -1-benzoyl-4- [3- (6-methoxyquinolin-4-yl) propyl] -3-vinylpiperidine are obtained in the form of a brown oil.

La (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-3-vinylpipéridine peut être obtenuepar application de la méthode décrite dans la demande de brevet FR 2354771.(3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -3-vinylpiperidine can be obtained by application of the method described in patent application FR 2354771.

Exemple 3Example 3

Dihlorhydrate de l’acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(3-fluorophénylthio)-2-éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (3-fluorophenylthio) -2-ethyl] piperidine-3-carboxylic acid hydrochloride

Un mélange de 0,54 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyI]-l-[2-(3-fiuorophénylthio)-2-éthyl]pipéridine-3-carboxylate de méthyle dans 4 cm3 deméthanol et 0,8 cm3 de soude aqueuse 5N est chauffé sous agitation à 60°C pendant20 heures. Après mélange des solvants sous pression réduite (5 kPa), à unetempérature voisine de 40°C, le résidu obtenu est repris dans 10 cm3 d’eau, puisacidifié par 0,4 cm3 d’acide chlorhydrique concentré. La solution est mélangée dansles mêmes conditions, puis le résidu obtenu est trituré dans un mélange dedichlorométhane-méthanol (90/10 en volumes). L’insoluble est filtré, lavé par 5 cm3de dichlorométhane. Le filtrat est séché sur sulfate de sodium, puis concentré souspression réduite (5 kPa), à une température voisine de 40°C. Lé résidu est trituré dans10 cm3 d’éther diisopropylique, puis additionné, sous agitation, de 1 cm3 d’étherdiisopropylique chlorhydrique 5N. Les cristaux sont séparés par filtration, puis lavéspar 2 fois 5 cm3 d’éther diisopropylique. Après séchage à l’air, on obtient 0,45 g dedichlorhydrate d’acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3-fluoro 1 2 0 2 2 179 phénylthio)-2-éthyl]pipéridine-3-carboxylique,_sous forme d’un solide amorphe decouleur jaune-pâle fondant au voisinage de 140°C en devenant pâteux.A mixture of 0.54 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluorophenylthio) -2-ethyl] piperidine-3- Methyl carboxylate in 4 cm3 of methanol and 0.8 cm3 of 5N aqueous sodium hydroxide is heated with stirring at 60 ° C for 20 hours. After mixing the solvents under reduced pressure (5 kPa), at a temperature in the region of 40 ° C., the residue obtained is taken up in 10 cm 3 of water and then acidified with 0.4 cm 3 of concentrated hydrochloric acid. The solution is mixed under the same conditions, then the residue obtained is triturated in a mixture of dichloromethane-methanol (90/10 by volume). The insoluble matter is filtered and washed with 5 cm3 of dichloromethane. The filtrate is dried over sodium sulphate and then concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. The residue is triturated in 10 cm3 of diisopropyl ether and then added, with stirring, 1 cm3 of 5N hydrochloric ether diisopropyl ether. The crystals are separated by filtration and then washed with twice 5 cm3 of diisopropyl ether. After drying in air, 0.45 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluoro) dihydrochloride are obtained. 2-phenylthio) -2-ethyl-piperidine-3-carboxylic acid, in the form of a yellow-pale amorphous solid melting at about 140 ° C., becoming pasty.

Spectre infra rouge (KBr) : 3058 et 3012 cm'1 (v CH aromatiques) ; 2935 et 2862 cm'1 (v CH2) ; 3000 et 2750 cm·' (v OH acide) ; 2800 et 1900 cm'1 (v N*H ( seld’amine tertiaire + sel de quinoline)) ; 1719 cm'1 (v C=O acide) ;1618 ;1600 ; 1578 ; 1541 etl496 cm'1 (v C=C noyaux aromatiques) ; 1274 cm'1 (v C-0acide ); 1251 et 1216 cm'1 (vas C-0 éther) ; 1021 cm'1 (vs C-0 éther + n C-O alcool) ;847 cm'1 (γ CH quinoline 4-6 disubstituée) ; 781 et 729 cm'1 (γ CH phényl 1-3disubstitué).Infrared spectrum (KBr): 3058 and 3012 cm -1 (aromatic CH); 2935 and 2862 cm -1 (v CH 2); 3000 and 2750 cm -1 acidic acid; 2800 and 1900 cm -1 (v N * H (tertiary amine salt + quinoline salt)); 1719 cm -1 (v C = O acid), 1618, 1600; 1578; 1541 and 1496 cm -1 (v C = C aromatic rings); 1274 cm -1 (v C-0 acid); 1251 and 1216 cm -1 (C 0 ether); 1021 cm -1 (vs C-O ether + n C-O alcohol); 847 cm -1 (γ CH 4-6 disubstituted quinoline); 781 and 729 cm -1 (γ-phenyl-3-disubstituted phenyl).

Spectre de masse (IE - m/z) : =482 (M*) ; 438 (M-CO2)+'; 341 (M-C7H6SF)+ pic debase ; 297 ; 341 (M- COJ*; 186 (C^H^NO*) ; 128 (C6H3SF) ; 36 (HCl*)Mass spectrum (IE - m / z): = 482 (M +); 438 (M-CO2) + '; 341 (M-C7H6SF) + peak debase; 297; 341 (M-COI); 186 (C₁ HH ^ NO *); 128 (C6H3SF); 36 (HCl *);

Le (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3-fluorophénylthio)-2-éthyl]pipéridine-3-carboxylate de méthyle peut être préparé de la manière suivante :Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluorophenylthio) -2-ethyl] piperidine-3-carboxylate can be prepared from the following way:

En opérant par analogie avec l’exemple 4 ci-après, mais à partir de chlorhydrate du(3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-carboxyIate de méthyle etde 2-bromo-l-(3-fluorophényl)thioéthane, on obtient 0,55 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(3-fluorophénylthio)-2-éthyl]pipéridme-3 -carboxylate de méthyle, sous forme d’une huile visqueuse de couleur jaune.By operating analogously with Example 4 below, but starting from methyl (2R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxyate hydrochloride and 2 -bromo-1- (3-fluorophenyl) thioethane gives 0.55 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3- Methyl fluorophenylthio) -2-ethyl] piperidin-3-carboxylate as a viscous yellow oil.

Spectre infra rouge (CC14)2949 cm'1 vCïl aliphatiques ;1737 "cm'1 vC=O ;1227 cm'1 vC-0 éther ;845 cm'1 yCH quinoline.Infrared spectrum (CCl 2) 2949 cm -1 aliphatic, 1737 cm -1 C = 01227 cm -1 vC-O ether, 845 cm -1 quinoline.

Le chlorhydrate de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-carboxylate de méthyle a été préparé dans les conditions de l’exemple 6.Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate hydrochloride was prepared under the conditions of Example 6.

Exemple 4Example 4

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(phényIthioéthyl)]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (phenylthioethyl)] piperidine-3-carboxylic acid

Une suspension de 0,7 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(phénylthioéthyl)]pipéridine-3-carboxylate de méthyle dans 5 cm3 de méthanoladditionnés de 2,9 cm3 de soude aqueuse N est agitée pendant 2 heures à unetempérature voisine de 80°C. La solution obtenue est neutralisée par 0,18 cm3 d’acideacétique, puis méiangée sous pression réduite (5 kPa), à une température voisine de40°C. Le résidu obtenu est purifié par chromatographie à pression atmosphérique sur 120 2 2 180 une colonne de gel de silice (granulométrie 40-63 μ ; diamètre 3 cm ; hauteur 20 cm),en éluant par un mélange de dichlorométhane-éthanol (90/10 en volumes), et enrecueillant des fractions de 20 cm1 * 3. Les fractions 21 à 52 sont réunies, concentréessous pression réduite (5 kPa), à une température voisine de 40°C. On obtient 0,53 gd’acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(phénylthioéthyl)]pipéridine-3-carboxylique, sous forme d’une huile de couleur beige.A suspension of 0.7 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (phenylthioethyl)] piperidine-3-carboxylate in 5 cm3 of methanoladditioned with 2.9 cm3 of aqueous sodium hydroxide N is stirred for 2 hours at a temperature in the region of 80.degree. The solution obtained is neutralized with 0.18 cm 3 of acetic acid and then mixed under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. The residue obtained is purified by chromatography at atmospheric pressure on a column of silica gel (particle size 40-63 μ, diameter 3 cm, height 20 cm), eluting with a mixture of dichloromethane-ethanol (90/10). in volumes), and collecting fractions of 20 cm 3. Fractions 21 to 52 are combined, concentrated under reduced pressure (5 kPa), at a temperature in the region of 40 ° C. 0.53 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (phenylthioethyl)] piperidine-3-carboxylic acid is obtained in the form of a beige colored oil.

Spectre de R.M.N. *H (400 MHz, (CD3)2SO d6, δ en ppm) : de 1,35 à 1,95 (mt : 7H) ; 2,28 (t large, J= 10,5 Hz : 1H) ; 2,43 (d large, J = 10,5 Hz : 1H) ; 2,59 (mt : 1H) ;2,64 (t, J = 7 Hz : 2H) ; 2,77 (mf : 1H) ; 2,93 (mf : 1H) ; 3,03 (mt : 2H) ; 3,13 (mt :2H) ; 3,95 (s : 3H) ; 7,21 (tt, J = 7,5 et 2 Hz : 1H) ; de 7,25 à 7,45 (mt : 7H) ; 7,93 (d,J = 9 Hz : 1H) ; 8,63 (d, J = 4,5 Hz : 1H).Spectrum of R.M.N. * H (400 MHz, (CD3) 2SO d6, δ in ppm): from 1.35 to 1.95 (mt: 7H); 2.28 (broad t, J = 10.5 Hz: 1H); 2.43 (d, J = 10.5 Hz: 1H); 2.59 (mt: 1H), 2.64 (t, J = 7 Hz: 2H); 2.77 (mf: 1H); 2.93 (mf: 1H); 3.03 (mt: 2H); 3.13 (mt: 2H); 3.95 (s: 3H); 7.21 (tt, J = 7.5 and 2 Hz: 1H); from 7.25 to 7.45 (mt: 7H); 7.93 (d, J = 9 Hz: 1H); 8.63 (d, J = 4.5 Hz: 1H).

Le (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -(2-phénylthioéthyl)]pipéridine-3-carboxylate de méthyle peut être préparé de la manière suivante : 1 g de chlorhydrate de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3- carboxylate de méthyle 1 g de carbonate de potassium sont agités à une températurevoisine de 20°C dans 100 cm3 d’acétonitrile pendant 20 minutes. Après addition de0,61 g de 2-bromo-l-phénylthioéthane préalablement dissous dans 5 cm3d’acétonitrile, le mélange est chauffé à une température voisine de 60°C pendant5 heures. Après addition de 20 cm3 de diméthylformamide et 0,61 g supplémentairede 2-bromo-l-phénylthioéthane, le chauffage est maintenu encore 8 heures30 minutes. Après refroidissement, le mélange réactionnel est filtré; la solutionobtenue est concentrée sous pression réduite (5 kPa), à une température voisine de70°C. Le résidu est repris dans 50 cm3 d’éthanol, puis concentré à nouveau dans lesmêmes conditions que ci-dessus. Le résidu est dilué par 30 cm3 d’eau, puis extrait par 3 fois 20 cm3 de dichlorométhane. Les extraits réunis sont séchés sur sulfate demagnésium, concentrés sous pression réduite (5 kPa), à une température voisine de40°C. On obtient 1 g d’une huile que l’on purifie par chromatographie à pressionatmosphérique sur une colonne de gel de silice (granulométrie 40-63 μ ; diamètre 3,5 cm ; hauteur 20 cm), en éluant par un mélange de dichlorométhane-éthanol (90/10en volumes), et en recueillant des fractions de 25 cm3. Les fractions 15 à 26 sontréunies, puis concentrées sous pression réduite (5 kPa), à une température voisine de40°C. On obtient 0,79 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(2-phénylthioéthyl)pipéridine-3-carboxylate de méthyle, sous forme d’une huile decouleur jaune. 12 0 2 2 181Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (2-phenylthioethyl)] piperidine-3-carboxylate can be prepared in the following manner: 1 g of Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate hydrochloride 1 g of potassium carbonate are stirred at a temperature of about 20 ° C. in 100 cc of dichloromethane. acetonitrile for 20 minutes. After addition of 0.61 g of 2-bromo-1-phenylthioethane previously dissolved in 5 cm3 of acetonitrile, the mixture is heated at a temperature of 60 ° C for 5 hours. After addition of 20 cm3 of dimethylformamide and 0.61 g addition of 2-bromo-1-phenylthioethane, the heating is maintained for 8 hours 30 minutes. After cooling, the reaction mixture is filtered; the solution obtained is concentrated under reduced pressure (5 kPa) at a temperature in the region of 70 ° C. The residue is taken up in 50 cm3 of ethanol and then concentrated again under the same conditions as above. The residue is diluted with 30 cm3 of water and then extracted with 3 times 20 cm3 of dichloromethane. The combined extracts are dried over magnesium sulphate and concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 1 g of an oil is obtained which is purified by atmospheric pressure chromatography on a column of silica gel (particle size 40-63 μ, diameter 3.5 cm, height 20 cm), eluting with a mixture of dichloromethane. ethanol (90:10 volumes), and collecting fractions of 25 cm3. The fractions 15 to 26 sontréunies, then concentrated under reduced pressure (5 kPa), at a temperature of 40 ° C. 0.79 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (2-phenylthioethyl) piperidine-3-carboxylate are obtained in the form of a yellow colored oil. 12 0 2 2 181

Le chlorhydrate de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyljpipéridine-3-carboxylate de méthyle peut être préparé dans les conditions de l’exemple 6.Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate hydrochloride can be prepared under the conditions of Example 6.

Exemple 6Example 6

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(3-phénylprop-2-ynyl)pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- (3-phenylprop-2-ynyl) piperidine-3-carboxylic acid

Une solution de 0,25 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(3-phénylprop-2-ynyl)pipéridine-3-carboxylate de méthyle dans 6 cm3 de méthanol estadditionnée de 0,41 cm3 de soude aqueuse 5N, puis chauffée à une températurevoisine de 57°C pendant 18 heures 30 minutes en atmosphère inerte. Le mélange estrefroidi puis concentré sous pression réduite (2 kPa), à une température voisine de40°C. Le résidu est repris par 10 cm3 d’eau, acidifié par 2 cm3 d’acide chlorhydriqueaqueux .N, concentré sous pression réduite (2 kPa), à une température voisine de45°C. Le résidu obtenu est trituré dans 10 cm3 d’un mélange de dichlorométhane-méthanol (90/10 en volumes), puis filtré. L’insoluble est lavé par 2 fois 10 cm3 dedichlorométhane. Les filtrats organiques réunis sont concentrés sous pression réduite(2 kPa), à une température voisine de 30°C. On obtient un résidu de 0,22 g que l’onagite dans un mélange de 20 cm3 d’eau et 15 cm3 de dichlorométhane. La phaseaqueuse est décantée, puis extraite par 3 fois 10 cm3 de dichlorométhane. Cette phaseaqueuse est concentrée à sec, sous pression réduite (5 kPa), à une température voisinede 40°C. Le résidu est trituré dans 10 cm3 d’un mélange diehîorométhane-méthanol(90/10 en volumes). L’insoluble est filtré, puis le gâteau est lavé par 5 cm3 du mêmemélange. Le filtrat est séché sur sulfate de magnésium, puis concentré sous pressionréduite, dans les mêmes conditions que précédemment, et enfin séché sous pressionpartielle (13 Pa), à une température voisine de 40°C pendant 2 heures. On obtient0,11 g d’acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(3-phénylprop-2-ynyl) pipéridine-3-carboxylique sous forme d’un solide meringué de couleur jaune-pâle, fondant aux environs de 166°C en devenant pâteux.A solution of 0.25 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylprop-2-ynyl) piperidine-3-carboxylate in 6 cm3 of methanol are added with 0.41 cm3 of 5N aqueous sodium hydroxide and then heated to a temperature of 57 ° C for 18 hours 30 minutes in an inert atmosphere. The mixture is cooled and then concentrated under reduced pressure (2 kPa), at a temperature of 40 ° C. The residue is taken up in 10 cm3 of water, acidified with 2 cm3 of HCl hydrochloric acid, concentrated under reduced pressure (2 kPa), at a temperature in the region of 45 ° C. The residue obtained is triturated in 10 cm3 of a mixture of dichloromethane-methanol (90/10 by volume), and then filtered. The insoluble material is washed with twice 10 cm3 of dichloromethane. The combined organic filtrates are concentrated under reduced pressure (2 kPa) at a temperature in the region of 30 ° C. A residue of 0.22 g is obtained which is stirred in a mixture of 20 cm3 of water and 15 cm3 of dichloromethane. The phasicosa is decanted, then extracted with 3 times 10 cm3 of dichloromethane. This phaser is concentrated to dryness under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. The residue is triturated in 10 cm3 of a mixture of dihloromethane-methanol (90/10 by volume). The insoluble material is filtered and the cake is washed with 5 cm3 of the same mixture. The filtrate is dried over magnesium sulfate, then concentrated under reduced pressure, under the same conditions as above, and finally dried under partial pressure (13 Pa), at a temperature of 40 ° C for 2 hours. 0.11 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylprop-2-ynyl) piperidine-3-carboxylic acid is obtained in the form of a pale yellow meringue meringue, melting at about 166 ° C becoming pasty.

Spectre infra rouge (KBr) : 2931 ; 2859 cm'1 (v CH^ ; 3000 et 2750 cm'1 (v OHacide) ; 2800 et 1900 cm'1 (v N+H ( sel d’amine tertiaire + sel de quinoîine));1719 cm'1 (v C=O acide) ; 1618 ; 1601 ;1542 et 1492 cm'1 (v C=C noyauxaromatiques) ; 1275 cm'1 (v C-O acide) ; 1225 cm'1 (vls C-0 éther) ; 1022 cm'1 (vs C-Oéther) ; 846 cm'1 ίγ CH quinoîine 4-6 disubstituée) ; 761 et 693 cm'1 (γ CH phénylmonosubstitué). 120 2 2 182Infra red spectrum (KBr): 2931; 2859 cm -1 (v CH 3) and 2750 cm -1 (v OH acid), 2800 and 1900 cm -1 (v N + H (tertiary amine salt + quinine salt)), 1719 cm -1 (v C = O acid), 1618, 1601, 1542 and 1492 cm -1 (v C = C aromatic nuclei), 1275 cm -1 (v CO acid), 1225 cm -1 (vls C-0 ether), 1022 cm -1 (vs C-Oether) 846 cm -1 ίγ CH 4-6 disubstituted quinoline); 761 and 693 cm -1 (γ-phenyl-substituted phenyl). 120 2 182

Spectre de masse (IE- m/z) 442 (M+) ; 398 (M-CO2/ ; 327 (M-C9H7)+ ; 283 ; 327 (M- CO2)+; 186 (CI2HI2ON*) ; 115 (C9H7+) ; 44 (CO2+) ; 36 (HCl*· pic de base) (3R,4R)-4-[3-(6-méthoxyquinoIin-4-yl)propyl]-l-(3-phénylprop-2-ynyl)pipéridine-3-carboxylate de méthyle A une solution agitée de 0,7 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(prop-2-ynyl)pipéridine-3-carboxylate de méthyle dans 12 cm3 d’acétonitrile, onajoute, sous atmosphère inerte, à une température voisine de 20°C, 0,138 g detétrakis(triphénylphosphine)palladium, 0,041 g de triphénylphosphine et 0,070 gd’iodure cuivreux. On ajoute ensuite 0,56 g d’iodobenzène, puis 0,51 cm3 detriéthylamine. Le mélange est agité pendant 22 heures à une température voisine de20°C, puis filtré. Le gâteau est lavé par 3 fois 10 cm3 d’acétonitrile. Les filtrats réunissont additionnés de 100 cm3 de dichlorométhane et 100 cm3 d’eau, puis agités. Laphase organique est décantée, lavée par 3 fois 50 cm3 d’une solution saturée dechlorure de sodium. Après séchage sur sulfate de magnésium, puis filtration, lasolution organique est mélangée sous pression réduite (2 kPa), à une températurevoisine de 40°C. On obtient 1,1 g d’une huile que l’on purifie par chromatographiesous pression d’argon (50 kPa), sur une colonne de gel de silice (granulométrie 40-63 μ ; diamètre 3 cm ; 65 g), en éluant par l’acétate d’éthyle, et en recueillant desfractions de 2,5 cm3. Les fractions 52 à 210 sont réunies, concentrées sous pressionréduite (2 kPa), à une température voisine de 35°C. On obtient 0,64 g de (3R,4R)-4-[3 -(6-méthoxyquinolin-4-yl)propyl]-1 -(3-phénylprop-2-ynyl)pipéridine-3-carboxylatede méthyle sous forme d’une huile de couleur brun-clair.Mass spectrum (EMI / z) 442 (M +); 398 (M-CO2 /; 327 (M-C9H7) +; 283; 327 (M-CO2) +; 186 (CI2HI2ON *); 115 (C9H7 +); 44 (CO2 +); 36 (HCl * · base peak) Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylprop-2-ynyl) piperidine-3-carboxylate To a stirred solution of 0.7 g methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-carboxylate in 12 cm3 of acetonitrile is added under inert atmosphere, at a temperature in the region of 20 ° C., 0.138 g of tetrakis (triphenylphosphine) palladium, 0.041 g of triphenylphosphine and 0.070 g of cuprous iodide, then 0.56 g of iodobenzene and 0.51 cm3 of triethylamine are added. The mixture is stirred for 22 hours at a temperature in the region of 20 ° C. and then filtered The cake is washed with acetonitrile (3 × 10 cc) The filtrates are combined with 100 cm 3 of dichloromethane and 100 cm 3 of water and then stirred. is decanted, washed with 3 times 50 cm3 of a saturated solution of chlorine After drying over magnesium sulfate and then filtering, the organic solution is mixed under reduced pressure (2 kPa) at a temperature of 40.degree. 1.1 g of an oil are obtained which is purified by chromatography under argon pressure (50 kPa), on a column of silica gel (particle size 40-63 μ, diameter 3 cm, 65 g), eluting with by ethyl acetate, and collecting fractions of 2.5 cm3. Fractions 52 to 210 are combined and concentrated under reduced pressure (2 kPa) at a temperature in the region of 35 ° C. 0.64 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylprop-2-ynyl) piperidine-3-carboxylated methyl ester are obtained in the form of 'a light brown oil.

Le (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-1 -(prop-2-ynyl)pipéridine-3-carboxylate de méthyle peut être préparé de la manière suivante : A une suspension agitée de 10 g de chlorhydrate de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-carboxylate de méthyle dans 100 cm3 dediméthylformamide anhydre, et sous atmosphère inerte, on ajoute, à une températurevoisine de 20°C, 14,7 cm3 de triéthylamine, puis au bout de 45 minutes, 3 cm3 debromure de propargyle dilués dans 10 cm3 de diméthylformamide anhydre. Après15 minutes d’agitation à une température voisine de 20°C, le mélange est chauffépendant 4 heures à une température voisine de 45 °C. Après refroidissement, le t mélange réactionnel est versé dans un mélange de 250 cm3 d’acétate d’éthyle et250 cm3 d’eau distillée. Le mélange est q.gité quelques minutes, puis la phase 120 2 2 183 organique est décantée. La phase aqueuse est extraite par 2 fois 250 cm3 d’acétated’éthyle. Les phases organiques sont réunies, lavées par 3 fois 200 cm3 d’eau distillée,séchées sur sulfate de magnésium. Après filtration, puis mélange du solvant souspression réduite (2 kPa), à une température voisine de 40°C, on obtient 7,8 g d’unehuile que l’on purifie par chromatographie sous pression d’argon (50 kPa), sur unecolonne de gel de silice (granulométrie 40-63 μ ; diamètre 7 cm ; 475 g), en éluant parl’acétate d’éthyle et en recueillant des fractions de 8 cm3. Les fractions 468 à 612 sontréunies, puis concentrées sous pression réduite (2 kPa), à une température voisine de45°C. On obtient 4,7 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(prop-2-ynyl)pipéridine-3-carboxylate de méthyle, sous forme d’huile de couleur orangée.Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-carboxylate can be prepared in the following manner: stirred suspension of 10 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate hydrochloride in 100 cm3 of anhydrous dimethylformamide, and under an inert atmosphere, added at a temperature of 20 ° C, 14.7 cm3 of triethylamine and then after 45 minutes, 3 cm3 of propargyl bromide diluted in 10 cm3 of anhydrous dimethylformamide. After stirring for 15 minutes at a temperature in the region of 20 ° C., the mixture is heated for 4 hours at a temperature in the region of 45 ° C. After cooling, the reaction mixture is poured into a mixture of 250 cm3 of ethyl acetate and 250 cm3 of distilled water. The mixture is stirred for a few minutes and then the organic phase is decanted. The aqueous phase is extracted with twice 250 cm3 of ethyl acetate. The organic phases are combined, washed with 3 times 200 cm3 of distilled water, dried over magnesium sulfate. After filtration, and then mixing the solvent under reduced pressure (2 kPa), at a temperature in the region of 40 ° C., 7.8 g of an oil are obtained which is purified by chromatography under argon pressure (50 kPa), on a silica gel column (particle size 40-63 μ, diameter 7 cm, 475 g), eluting with ethyl acetate and collecting 8 cm 3 fractions. Fractions 468 to 612 are combined and then concentrated under reduced pressure (2 kPa) at a temperature in the region of 45 ° C. 4.7 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-carboxylate are obtained in the form of orange-colored oil.

Le chlorhydrate de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-carboxylate de méthyle peut être préparé de la manière suivante : A une suspension agitée de 4,29 g d’acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(tert-butyloxycarbonyl)pipéridine-3-carboxylique dans 50 cm3 deméthanol et refroidie à une température voisine de -30°C par un bain réfrigérantd’acétone et de carboglace, on ajoute goutte à goutte 2 cm3 de chlorure de thionyle. Lasolution obtenue est ramenée à une température voisine de 20°C, et le mélangeréactionnel est agité pendant 16 heures à cette température. Après mélange de lasolution sous pression réduite (5 kPa), à une température voisine de 40°C, le résiduobtenu est trituré dans 30 cm3 environ d’éther diisopropylique. Les cristaux obtenussont essorés, lavés par 2 fois 10 cm3 d’éther diisopropylique, puis séchés à l’air. Onobtient 4,20 g de chlorhydrate de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-carboxylate de méthyle, sous forme d’un solide de couleur jaune clair,fondant en se ramollissant à une température voisine de 140°C. L’acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(tert-butyloxycarbonyl)pipéridine-3-carboxylique peut être préparé de la manière suivante : 3 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-3-vinylpipéridine sont dissousdans 3 cm3 d’acétone. A cette solution, refroidie à une température voisine de 5°C parun bain de glace et d’acétone, on ajoute sous agitation 14,5 cm3 d’acide sulfurique 3Mpréalablement refroidis à cette même température. A la solution obtenue, on ajoute en30 minutes une solution de 4,64 g de permanganate de sodium monohydraté dans25 cm3 d’eau, en maintenant la température entre 0 et 7°C. Le mélange réactionnel estagité pendant 4 heures à une température comprise entre 10 et 17°C. La masse 120 22 184 réactionnelle est filtrée ; l’insoluble est lavé par 2 fois 10 cm3 d’eau. On obtient d’unepart une solution de couleur orangée, et d’autre part une masse minérale de couleurnoire. La solution orangée est amenée à pH 10 par addition de 4,6 g de carbonate desodium. Le mélange est filtré : on obtient une solution (1) et un insoluble minéral (2).La masse minérale de couleur noire est agitée pendant 30 minutes dans 20 cm3 d’eauaprès que le pH ait été amené à 12 par addition de 2 cm3 de lessive de potasse. Aprèsfiltration du mélange, on obtient une solution (3) et un insoluble minéral (4). Lesinsolubles (2) et (4) sont agités pendant 15 minutes dans 15 cm3 d’eau additionnés de3 cm3 de lessive de potasse. La suspension est filtrée. On obtient une solution (5). Lessolutions aqueuses (1), (3) et (5) sont réunies, additionnées de 2,31 g de di-tertiobutyldicarbonate, et agitées pendant 15 heures à une température voisine de 20°C. Lemélange est extrait par 6 fois 10 cm3 d’acétate d’éthyle. Les phases organiques sontréunies, lavées par 20 cm3 d’eau, puis par 20 cm3 d’une solution aqueuse saturée dechlorure de sodium. Après séchage sur sulfate de sodium, filtration, puisconcentration sous pression réduite (5 kPa), à une température voisine de 35°C, onobtient 2,86 g d’acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(tert-butyloxycarbonyl) pipéridine-3-carboxylique, sous forme d’un solide de couleurbeige, devenant pâteux à 154°C.Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate hydrochloride can be prepared in the following manner: To a stirred suspension of 4.29 g d (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) piperidine-3-carboxylic acid in 50 cm3 of ethanol and cooled to a temperature in the region of -30 C. With a cooling bath of acetone and dry ice, 2 cm 3 of thionyl chloride are added dropwise. The resulting solution is brought to a temperature of 20 ° C, and the reaction mixture is stirred for 16 hours at this temperature. After mixing the solution under reduced pressure (5 kPa) at a temperature in the region of 40 ° C., the residue obtained is triturated in approximately 30 cm3 of diisopropyl ether. The crystals obtained are drained, washed with twice 10 cm3 of diisopropyl ether and then dried in air. 4.20 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate hydrochloride are obtained in the form of a light yellow solid, m.p. softening at a temperature of about 140 ° C. (3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) piperidine-3-carboxylic acid can be prepared in the following manner: 3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -3-vinylpiperidine are dissolved in 3 cm3 of acetone. To this solution, cooled to a temperature in the region of 5 ° C. with a bath of ice and acetone, 14.5 cm 3 of 3M sulfuric acid, previously cooled at this temperature, are added with stirring. To the resulting solution was added in 30 minutes a solution of 4.64 g of sodium permanganate monohydrate in 25 cm3 of water, keeping the temperature between 0 and 7 ° C. The reaction mixture is stirred for 4 hours at a temperature between 10 and 17 ° C. The reaction mass is filtered; the insoluble material is washed with twice 10 cm3 of water. One obtains an orange-colored solution on the one hand, and a black-colored mineral mass on the other. The orange solution is brought to pH 10 by the addition of 4.6 g of sodium carbonate. The mixture is filtered: a solution (1) and an insoluble mineral (2) are obtained. The black colored mineral mass is stirred for 30 minutes in 20 cm 3 of water after the pH has been brought to 12 by addition of 2 cm 3 of potash liquor. After filtration of the mixture, a solution (3) and an insoluble mineral (4) are obtained. The insolubles (2) and (4) are stirred for 15 minutes in 15 cm3 of water with 3 cm3 of potassium hydroxide solution. The suspension is filtered. A solution (5) is obtained. Aqueous solutions (1), (3) and (5) are combined, supplemented with 2.31 g of di-tert-butyldicarbonate, and stirred for 15 hours at a temperature of 20 ° C. Lemix is extracted with 6 times 10 cm3 of ethyl acetate. The organic phases sontréunies, washed with 20 cm3 of water, then with 20 cm3 of a saturated aqueous solution of sodium chloride. After drying over sodium sulphate, filtration and puisconcentration under reduced pressure (5 kPa) at a temperature in the region of 35 ° C., 2.86 g of (3R, 4R) -4- [3- (6-methoxyquinolinic acid) are obtained. 4-yl) propyl] -1- (tert-butyloxycarbonyl) piperidine-3-carboxylic acid, as a breeze color solid, becoming pasty at 154 ° C.

La (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-3-vinylpipéridine peut être obtenuepar application de la méthode décrite dans la demande de brevet FR 2354771.(3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -3-vinylpiperidine can be obtained by application of the method described in patent application FR 2354771.

Exemple 7Example 7

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yI)propyl]-l-[3-(2-fluorophényl)prop-2-ynyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenyl) prop-2-ynyl] piperidine-3-carboxylic acid

Une solution de 0,28 g de(3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2-fluorophényl)prop-2-ynyl]pipéridine-3-carboxylate de méthyle dans 10 cm3 deméthanol est additionnée de 0,44 cm3 de soude aqueuse 5N, puis chauffée à unetempérature voisine de 57°C pendant 20 heures. Après refroidissement, la solution estmélangée sous pression réduite (2 kPa), à une température voisine de 40°C. Onobtient un résidu de 0,41 g qui est repris par 20 cm3 d’eau additionnés de 3,5 cm3d’acide chlorhydrique IN. Après extraction de la phase aqueuse par 5 fois 15 cm3 dedichlorométhane, la phase aqueuse est concentrée à sec sous pression réduite (5 kPa),à une température voisine de 40°C. Le résidu obtenu est trituré dans 10 cm3 d’unmélange de dichlorométhane-méthanol (90/10 en volumes). L’insoluble est filtré, puis 120 22 185 le gâteau est lavé par 10 cm3 du même mélange. Le filtrat est séché sur sulfate demagnésium, puis concentré sous pression réduite (5 kPa), à une température voisinede 40°C, et enfin séché sous vide (13 Pa), à une température voisine de 40°C pendant2 heures. On obtient 0,15 g d’acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2-fluorophényl)prop-2-ynyl3pipéridine-3-carboxylique sous forme d’un solidemeringué de couleur jaune-pâle, fondant aux environs de 154°C, en devenant pâteux.A solution of 0.28 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenyl) prop-2-ynyl] piperidine-3 In 10 cm3 of methanol-methyl metboxylate is added 0.44 cm3 of 5N aqueous sodium hydroxide and then heated to a temperature of 57 ° C for 20 hours. After cooling, the solution ismixed under reduced pressure (2 kPa), at a temperature in the region of 40.degree. A residue of 0.41 g is obtained which is taken up in 20 cm3 of water added with 3.5 cm3 of 1N hydrochloric acid. After extraction of the aqueous phase with 5 times 15 cm3 of dichloromethane, the aqueous phase is concentrated to dryness under reduced pressure (5 kPa), at a temperature in the region of 40 ° C. The residue obtained is triturated in 10 cm3 of a mixture of dichloromethane-methanol (90/10 by volume). The insoluble material is filtered and then the cake is washed with 10 cm3 of the same mixture. The filtrate is dried over magnesium sulfate, then concentrated under reduced pressure (5 kPa), at a temperature in the region of 40 ° C., and finally dried under vacuum (13 Pa) at a temperature in the region of 40 ° C. for 2 hours. 0.15 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenyl) prop-2-ynyl) piperidine-3-acid is obtained. carboxylic acid in the form of a solid yellow-pale solid, melting at about 154 ° C, becoming pasty.

Spectre infra rouge (KBr) : 3057 cm*1 (v CH aromatiques) ; 2933 ; 2864 cm*' (v CH2) ;3000 ; 2750 cm*1 (v OH acide) ; 2800 et 1900 cm*1 (v N+H ( sel d’amine tertiaire + selde quinoline)) ; 1722 cm*1 (v C=O acide) ; 1618 ;1601 ;1542 et 1493 cm*1 (v C=Cnoyaux aromatiques) ; 1275 cm*1 (v C-0 acide) ; 1217 cm*1 (vas C-0 éther) ; 1022 cm*1(vs C-0 éther) ; 847 cm*' (γ CH quinoline 4-6 disubstituée) ; 765 cm*1 (y CH phénylorthodisubstitué).Infra red spectrum (KBr): 3057 cm -1 (v CH aromatics); 2933; 2864 cm -1 (v CH 2); 2750 cm -1 acidic (OH); 2800 and 1900 cm * 1 (v N + H (tertiary amine salt + quinoline salt)); 1722 cm -1 (v C = O acid); 1618; 1601; 1542 and 1493 cm * 1 (v C = aromatic rings); 1275 cm -1 (v C-0 acid); 1217 cm -1 (C 0 ether); 1022 cm -1 (vs C-O ether); 847 cm -1 (γ CH 4-6 disubstituted quinoline); 765 cm -1 phenylorthodisubstituted).

Spectre de masse : (DCI) m/z=461 MH+ (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(3-(2-fluorophényl)prop-2-ynyllpipéridine-3-carboxylate de méthyle A une solution agitée de 0,7 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(prop-2-ynyl)pipéridine-3-carboxylate de méthyle dans 14 cm3 d’acétonitrile, onajoute, à une température voisine de 20°C et sous atmosphère inerte, 0,041 g detétrakjs(tr.iphénylphosphine)palladium et 0,070 g d’iodurc cuivreux. On ajoute ensuite0,32 cm3 de fiuoro-1 iodo-2 benzène et 0,51 cm3 de triéthylamine. Le mélange estagité à une température voisine de 20°C pendant 20 heures. Le mélange réactionnelest filtré, le gâteau lavé par 3 fois 10 cm3 d’acétonitrile. Les filtrats réunis sont reprissous agitation par un mélange de 100 cm3 de dichlorométhane et 100 cm3 d’eau. Laphase organique est décantée, lavée par 3 fois 50 cm3 d’une solution saturée dechlorure de sodium, séchée sur sulfate de magnésium, puis, après filtration,concentration sous pression réduite (2 kPa), à une température voisine de 35°C. Lerésidu obtenu est purifié par chromatographie sous pression d’argon (50 kPa), sur unecolonne de gel de silice (granulométrie 40-63 μ ; diamètre 4 cm ; hauteur 14 cm), enêîuant par de l’acétate d’éthyle, et en recueillant des fractions de 2 cm3. Les fractions33 à 160 sont réunies, puis mélangées sous pression réduite (2 kPa), à unetempérature voisine de 40°C. On obtient 0,56 g de (3R,4R)-4-[3-(6-méthoxyquinolin- 4-yl)propyl]-1 -[3-i2-fluorophényl)prop-2~ynyl]pipéridine-3-carboxylate de méthyle,sous forme d’une huile de couleur brun-clair. 120 22 186Mass Spectrum: (INN) m / z = 461 MH + (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (2-fluorophenyl) prop-2-) Methylpiperidine-3-carboxylate To a stirred solution of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine (0.7 g) In a mixture of acetonitrile (14 cm3) and acetonitrile (14 cc), 0.041 g of palladium (triphenylphosphine) palladium and 0.070 g of cuprous iodide are added at a temperature in the region of 20.degree. cm 3 of 1-fluoro-2-iodo-benzene and 0.51 cm 3 of triethylamine The mixture is stirred at a temperature in the region of 20 ° C. for 20 hours The reaction mixture is filtered and the cake is washed with 3 times 10 cm 3 of acetonitrile. The combined filtrates are then stirred with a mixture of dichloromethane (100 cc) and water (100 cc) .The organic phase is decanted, washed with saturated sodium chloride solution (3 × 50 cc), dried over magnesium sulphate and then dried. filtration, concentration under reduced pressure (2 kPa), at a temperature in the region of 35 ° C. The residue obtained is purified by chromatography under argon pressure (50 kPa), on a silica gel column (particle size 40-63 μ, diameter 4 cm, height 14 cm), using ethyl acetate, and in vacuo. collecting 2 cm3 fractions. Fractions33 to 160 are combined and then mixed under reduced pressure (2 kPa) at a temperature in the region of 40 ° C. 0.56 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (3-i2-fluorophenyl) prop-2-ynyl] piperidine-3-carboxylate are obtained. of methyl, in the form of a light brown oil. 120 22 186

Le (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(prop-2-ynyl)pipéridine-3-carboxylate de méthyle a été préparé dans les conditions de l’exemple 6.Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-carboxylate was prepared under the conditions of the example 6.

Exemple 8Example 8

Dichlorhydrate de l’acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-fluorophényl)prop-2-ynyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop-2-ynyl] piperidine-3-carboxylic acid dihydrochloride

Une solution de 0,66 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-fluorophényl)prop-2-ynyl]pipéridine-3-carboxylate de méthyle est additionnée de 10.5 cm3 d'une solution aqueuse d'acide chlorhydrique 6N, puis chauffée à unetempérature voisine de 100°C pendant 3 heures à l'issue desquelles sont additionnés 3.5 cm3 supplémentaires de solution aqueuse d'acide chlorhydrique 6N. Après4 heures, le mélange réactionnel est refroidi à une température voisine de 40°C puisconcentré sous pression réduite (2 kPa), à une température voisine de 60°C. Le résiduobtenu est repris dans 10 cm3 d’eau et 8 cm3 de dichlorométhane, puis décanté. Laphase aqueuse est extraite 2 fois par 6 cm3 de dichlorométhane. La solution aqueuseest concentrée à sec sous pression réduite (1 kPa), à une température voisine de 50°C.Le résidu obtenu est dissout dans 5 cm3 d’un mélange dichlorométhane-méthanol(90/10 en volumes), séché sur sulfate de sodium, puis, après filtration, le solvant estmélangeé sous pression réduite (1 kPa), à une température voisine de 40°C. Le résiduest repris dans un mélange de propanoI-2 et d'éther d'isopropyle, dissous à chaud, puisfiltré sur papier. Le filtrat est refroidi à une température voisine de 25°C puis mélangésous pression réduite (1 kPa), à une température voisine de 45°C. Le résidu est reprisdans 10 cm3 d’un mélange dichlorométhane-méthanol (90/10 en volumes) etreconcentré dans les mêmes conditions. On obtient 0,44 g de dichlorhydrate de l’acide(3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-fluorophényl)prop-2-ynyljpipéridine-3-carboxylique, sous forme d’une meringue de couleur jaune, fondant auxenvirons de 222°C, en devenant pâteux.A solution of 0.66 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop-2-ynyl] piperidine-3 10.5 cm 3 of an aqueous solution of 6N hydrochloric acid are added to the methylcarboxylate and then heated at a temperature in the region of 100 ° C. for 3 hours, after which an additional 3.5 cm 3 of aqueous 6N hydrochloric acid solution are added. . After 4 hours, the reaction mixture is cooled to a temperature of 40 ° C puisconcentré under reduced pressure (2 kPa) at a temperature of 60 ° C. The residue obtained is taken up in 10 cm3 of water and 8 cm3 of dichloromethane and decanted. Aqueous Laphase is extracted twice with 6 cm3 of dichloromethane. The aqueous solution is concentrated to dryness under reduced pressure (1 kPa), at a temperature in the region of 50 ° C. The residue obtained is dissolved in 5 cm 3 of a dichloromethane-methanol mixture (90/10 by volume), dried over sodium sulfate. sodium, then, after filtration, the solvent ismixed under reduced pressure (1 kPa), at a temperature of 40 ° C. The residue is taken up in a mixture of propanol-2 and isopropyl ether, dissolved hot, and then filtered through paper. The filtrate is cooled to a temperature in the region of 25 ° C. and then mixed under reduced pressure (1 kPa) at a temperature in the region of 45 ° C. The residue is taken up in 10 cm3 of a dichloromethane-methanol mixture (90/10 by volume) and concentrated under the same conditions. 0.44 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop-2-ynyl] piperidine dihydrochloride is obtained. -3-carboxylic acid, in the form of a yellow meringue, melting at 222 ° C, becoming pasty.

Spectre de R.M.N. (400 MHz, (CD3)2SO d6, δ en ppm) : de 1,20 à 2,15 (mf : 6H) ;2,35 (mf : 1 H) ; de 3,00 à 3,90 (mt : 7H) ; 4.02 (s : 3H) ; 4,40 (s large : 2H) ; de 7,25 à7,55 (mt : 4H) ; 7,60 (s large : 1H) ; 7,75 (dd, J = 9 et 2 Hz : 1H) ; 7,82 (d, J = 5 Hz :1H) ; 8,27 (d, J = 9 Hz : 1H) ; 8,97 (d, J = 5 Hz :1) ; de 11,15 à 11,45 (mf étalé : 1H). (3R,4R)T4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-fluorophényl)prop-2-ynyl]pipéridine-3-carboxylate de méthyle \ 12022¾ 187 A une solution agitée de 1,2 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propylj-1 -[prop-2-ynyl]pipéridine-3-carboxylate de méthyle dans 25 cm3 d’acétonitrile, onajoute, sous atmosphère inerte et à une température voisine de 20°C, 0,07 g detriphénylphosphine, 0,237 g de tétrakis(triphénylphosphine)palladium et 0,12 gd’iodure cuivreux. On ajoute ensuite 0,56 cm3 de l-fluoro-3-iodo-benzène et 0,88 cm3de triéthylamine. Après agitation pendant 20 heures à une température voisine de20°C, le mélange réactionnel est filtré sur Célite et le gâteau est lavé par del’acéfonitrile. Le filtrat est mélangée sous pression réduite (2 kPa), à une températurevoisine de 35°C. Le résidu obtenu est repris par un mélange de 80 cm3 dedichlorométhane et 80 cm3 d’eau. Après décantation, la phase organique est lavée par3 fois 50 cm3 d’une solution saturée de chlorure de sodium. La solution organique estséchée sur sulfate de magnésium, filtrée, puis concentrée sous pression réduite(2kPa), à une température voisine de 40°C. On obtient 1,91 g d’une huile que l’onpurifie par chromatographie sous pression d’argon (50 kPa), sur une colonne de gel desilice (granulométrie 40-63 μ ; diamètre 3 cm ; 77 g), en éluant par l’acétate d’éthyle,et en recueillant des fractions de 5 cm3. Les fractions contenant le produit attendu sontréunies, puis mélangées sous pression réduite (2 kPa), à une température voisine de40°C. On obtient 1,08 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3~fluorophényl)prop-2-ynyl]pipéridine-3-carboxylate de méthyle, sous forme d’unehuile de couleur jaune.Spectrum of R.M.N. (400 MHz, (CD3) 2SO d6, δ in ppm): from 1.20 to 2.15 (mf: 6H), 2.35 (mf: 1H); from 3.00 to 3.90 (mt: 7H); 4.02 (s: 3H); 4.40 (brs: 2H); from 7.25 to 7.55 (mt: 4H); 7.60 (s wide: 1H); 7.75 (dd, J = 9 and 2 Hz: 1H); 7.82 (d, J = 5 Hz: 1H); 8.27 (d, J = 9 Hz: 1H); 8.97 (d, J = 5 Hz: 1); from 11.15 to 11.45 (mf spread: 1H). (3R, 4R) Methyl 4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop-2-ynyl] piperidine-3-carboxylate 12022¾ 187 stirred solution of 1.2 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [prop-2-ynyl] piperidine-3-carboxylate in 25 cm3 d acetonitrile is added, under an inert atmosphere and at a temperature of 20 ° C, 0.07 g of triphenylphosphine, 0.237 g of tetrakis (triphenylphosphine) palladium and 0.12 g of cuprous iodide. 0.56 cm3 of 1-fluoro-3-iodobenzene and 0.88 cm3 of triethylamine are then added. After stirring for 20 hours at a temperature in the region of 20 ° C., the reaction mixture is filtered through Celite and the cake is washed with acetonitrile. The filtrate is mixed under reduced pressure (2 kPa) at a temperature of about 35 ° C. The residue obtained is taken up in a mixture of 80 cm 3 of dichloromethane and 80 cm 3 of water. After decantation, the organic phase is washed with 3 times 50 cm3 of a saturated solution of sodium chloride. The organic solution is dried over magnesium sulphate, filtered and then concentrated under reduced pressure (2 kPa) at a temperature of 40 ° C. 1.91 g of an oil which is purified by chromatography under argon pressure (50 kPa), on a desilice gel column (particle size 40-63 μ, diameter 3 cm, 77 g), eluting with ethyl acetate, and collecting 5 cm3 fractions. The fractions containing the expected product are then combined and then mixed under reduced pressure (2 kPa) at a temperature in the region of 40 ° C. 1.08 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop-2-ynyl] piperidine-3 are obtained. methyl carboxylate, in the form of a yellow oil.

Le (3R;4R)-4-[3~(6-méthoxyquinolin-4-yl)propyl]-l-[pfop-2-ynyl]pipéridine-3-carboxylate de méthyle a été préparé dans les conditions de l’exemple 6.Methyl (3R; 4R) -4- [3 ~ (6-methoxyquinolin-4-yl) propyl] -1- [pfop-2-ynyl] piperidine-3-carboxylate was prepared under the conditions of the example 6.

Exemple 10Example 10

Trichlorhydrate de l’acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(l,3-thiazol-2-ylthioéthyI)]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (1,3-thiazol-2-ylthioethyl)] piperidine-3-carboxylic acid trihydrochloride

Un mélange de 0,3 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(2-(1,3-thiazol-2-ylthioéthyl)]pipéridine-3-carboxylate de méthyle et de 0,44 cm3 de soudeaqueuse 5N dans 2,5 cm3 de méthanol est chauffé à une température voisine de 60°C,sous agitation, pendant 20 heures. Après refroidissement, le mélange réactionnel estmélangé sous pression réduite (5 kPa), à une température voisine de 40°C ; le résiduest repris dans 5 cm3 d’eau, puis acidifié par addition de 1 cm3 d’acide chlorhydriqueà 35 %. Le mélange est mélangé dans les mêmes conditions que ci-dessus, puis lerésidu obtenu est trituré dans 10 cm3 d’un mélange de dichlorométhane-méthanol 120 2 2 158 (90/10 en volumes). Après filtration de l’insoluble, le filtrat est mélangé sous pressionréduite (5 kPa), à une température voisine de 40°C. On obtient 0,34 g detrichlorhydrate de l’acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(l,3-thiazol-2-ylthioéthyl)]pipéridine-3-carboxylique, sous forme d’une meringue de 5 couleur jaune-pâle.A mixture of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (2- (1,3-thiazol-2-ylthioethyl)] piperidine, (0.3 g) Methyl 3-carboxylate and 0.44 cm3 of 5N weld in 2.5 cm3 of methanol is heated at a temperature of 60 ° C., with stirring, for 20 hours.When the mixture is cooled, it is mixed under reduced pressure ( 5 kPa), at a temperature of 40 ° C, the residue is taken up in 5 cm3 of water, then acidified by addition of 1 cm3 of 35% hydrochloric acid.The mixture is mixed under the same conditions as above, then the residue obtained is triturated in 10 cm3 of a mixture of dichloromethane-methanol (90/10 by volume) After filtration of the insoluble matter, the filtrate is mixed under reduced pressure (5 kPa) at a similar temperature. 40 ° C. 0.34 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1,3-thiazol) hydrochloride is obtained. -2-ylthioéthyl)] piperidin-3-carb oxylic, in the form of a yellow-pale meringue.

Spectre infra rouge (KBr) : 3097 cm'1 (v CH thiazole) ; 3058 et 3012 cm'1 (v CHaromatiques) ; 2929 et 28615 cm'1 (v CH2) ; 3000 et 2750 cm'1 (v OH acide) ; 2800et 1900 cm'1 (v ΝΉ ( sel d’amine tertiaire + sel de quinoline)) ; 1715 cm'1 (v C=Oacide) ; 1617 ; 1600 ;1543 et 1496 cm'1 (v C=C noyaux aromatiques) ; 1274 cm'1 (v 10 C-0 acide) ; 1250 et 1219 cm'1 (vas C-0 éther) ; 1020 cm'1 (vs C-O éther + v C O alcool) ; 846 cm'1 (γ CH quinoline 4-6 disubstituée) ; 740 cm'1 (γ CH thiazole).Infrared spectrum (KBr): 3097 cm -1 (v CH thiazole); 3058 and 3012 cm -1 (v CH aromatics); 2929 and 28615 cm -1 (v CH 2); 3000 and 2750 cm -1 (acidic OH); 2800 and 1900 cm -1 (v ΝΉ (tertiary amine salt + quinoline salt)); 1715 cm -1 (v C = acid); 1617; 1600, 1543 and 1496 cm -1 (v C = C aromatic rings); 1274 cm -1 (v C0 0 acid); 1250 and 1219 cm -1 (C 0 ether); 1020 cm -1 (vs C-O ether + v C O alcohol); 846 cm -1 (γ CH 4-6 disubstituted quinoline); 740 cm -1 (γ-CH thiazole).

Spectre de masse (IE - m/z) : 471 (M4) ; 355 (M-C3H2NS2)+ ; 341 (M-C4H4NS2)+ picde base ; 297 ; 341 (M- CO2)+; 186 (C12H12NO+) ; 117 (C3H3NS2+) ; 44 (CO,4). (3R,4R)-4"[3-(6-méthoxyquinoIin-4-yI)propyl]-l-[2-(l,3-thiazol-2-ylthîoéthyl)] 15 pipéridine-3-carboxyIate de méthyleMass spectrum (IE - m / z): 471 (M4); 355 (M-C3H2NS2) +; 341 (M-C4H4NS2) + picbase; 297; 341 (M-CO2) +; 186 (C12H12NO +); 117 (C3H3NS2 +); 44 (CO, 4). Methyl (3R, 4R) -4- [3- (6-methoxyquinyl-4-yl) propyl] -1- [2- (1,3-thiazol-2-ylthethyl)] piperidine-3-carboxyIate

En opérant par analogie avec l’exemple 4, mais à partir de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-carboxylate de méthyle et de 2-bromo-l-[(l,3-thiazol-2-yl)thio]éthane, on obtient 0,31 g de (3R,4R)-4-[3-(6-méthoxyquinolin- 4-yl)propyl]-l-[2-(l ,3-thiazol-2-ylthioéthyl)]pipéridine-3-carboxylate de méthyle, 20 sous forme d’une laque de couleur orangée.By analogy with Example 4, but starting from methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate and 2-bromo-1 - [(1,3-thiazol-2-yl) thio] ethane gives 0.31 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [ Methyl 2- (1,3-thiazol-2-ylthioethyl)] piperidine-3-carboxylate as an orange-colored lacquer.

Spectre de R.M.N. Ή (300 MHz, (CD3)2SO d6, δ en ppm) : de 1,30 à 1,85 (mt : 7H) ;de 2,20 à 2,35 (mt : 1H) ; 2,35 (dd, J = 11 et 3 Hz : 1H) ; de 2,50 à 2,85 (mt : 5H) ;3,03 (t, J = 7 Hz : 2H) ; de 3,25 à 3,40 (mt : 2H) ; 3,53 (s : 3H) ; 3,94 (s : 3H) ; 7,31(d, J = 5 Hz : 1H) ; 7,35 (d, J = 2,5 Hz : 1H) ; 7,40 (dd, J = 9 et 2,5 Hz : 1H) ; 7,63 (d, 25 J = 3,5 Hz : 1H) ; 7,72 (d, J = 3,5 Hz : 1H) ; 7,93 (d, J = 9 Hz : 1H) ; 8,63 (d, J = 5Hz : 1H).Spectrum of R.M.N. Ή (300 MHz, (CD3) 2SO d6, δ in ppm): from 1.30 to 1.85 (mt: 7H), from 2.20 to 2.35 (mt: 1H); 2.35 (dd, J = 11 and 3 Hz: 1H); 2.50 to 2.85 (mt: 5H), 3.03 (t, J = 7 Hz: 2H); from 3.25 to 3.40 (mt: 2H); 3.53 (s: 3H); 3.94 (s: 3H); 7.31 (d, J = 5 Hz: 1H); 7.35 (d, J = 2.5 Hz: 1H); 7.40 (dd, J = 9 and 2.5 Hz: 1H); 7.63 (d, J = 3.5 Hz: 1H); 7.72 (d, J = 3.5 Hz: 1H); 7.93 (d, J = 9 Hz: 1H); 8.63 (d, J = 5Hz: 1H).

Exemple 11Example 11

Chlorhydrate de l’acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2-fluorophénylthio)éthyl]pipéridine-3-carboxylique 30 On agite pendant 20 heures à une température voisine de 60°C un mélange de 0,12 g(3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propvl]-l-[2-(2-fluorophénylthio)éthyl]pipéridine-3-carboxylate de méthyle, 0,6 cm3 de soude aqueuse N dans 1,8 cm3 de 120 2 2 189 méthanol. Le mélange réactionnel est mélangeé sous pression réduite (5 kPa), à unetempérature voisine de 40°C. Le résidu obtenu est repris par 5 cm3 d’eau, et acidifiépar 1 cm3 d’acide chlorhydrique aqueux 2N. Le mélange est à nouveau mélangé dansles mêmes conditions que ci-dessus, puis, le nouveau résidu est trituré dans 5 cm3d’un mélange de dichlorométhane-méthanol (90/10 en volumes). Après filtration etmélange du filtrat sous pression réduite (5 kPa), à une température voisine de 40°C, lerésidu obtenu est trituré dans 3 cm3 d’éther diisopropylique. L’insoluble est filtré, lavépar 2 fois 1 cm3 d’éther diisopropylique, séché à l’air. On obtient 0,14 g dechlorhydrate de l’acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2-fluorophényl thio)éthyl]pipéridine-3-carboxylique, sous forme d’un solide de couleurbeige fondant, en se ramollissant, vers 148°C.(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (2-fluorophenylthio) ethyl] piperidine-3-carboxylic acid hydrochloride is stirred for 20 hours; at a temperature in the region of 60 ° C a mixture of 0.12 g (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (2- (2-fluorophenylthio) ethyl) ] Piperidine-3-carboxylic acid methyl ester, 0.6 cm3 of N aqueous sodium hydroxide in 1.8 cm3 of 120 2 2 methanol. The reaction mixture is mixed under reduced pressure (5 kPa) at a temperature of 40 ° C. The residue obtained is taken up in 5 cm3 of water and acidified with 1 cm3 of 2N aqueous hydrochloric acid. The mixture is again mixed under the same conditions as above, then the new residue is triturated in 5 cm3 of a mixture of dichloromethane-methanol (90/10 by volume). After filtration and mixing of the filtrate under reduced pressure (5 kPa), at a temperature in the region of 40 ° C., the residue obtained is triturated in 3 cm 3 of diisopropyl ether. The insoluble material is filtered, washed with twice 1 cm3 of diisopropyl ether and air-dried. 0.14 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-fluorophenylthio) ethyl] piperidine-3 hydrochloride is obtained. -carboxylic, in the form of a solid dye beige fondant, softening, about 148 ° C.

Spectre infra rouge (KBr) : 3058 et 3013 cm'1 (v CH aromatiques) ; 2934 et 2862 cm"1(v CH2) ; 3000 et 2750 cm'1 (v OH acide) ; 2800 et 1900 cm'1 (v hfH ( sel d’aminetertiaire + sel de quinoline)) ; 1719 cm'1 (v C=O acide); 1618 ; 1600; 1541 et 1497cm'1 (v C=C noyaux aromatiques) ; 1276 cm'1 (v C-O acide) ; 1251 et 1219 cm'1 (vasC-0 éther) ; 1022 cm'1 (vs C-0 éther + n C-0 alcool) ; 847 cm'1 (γ CH quinoline 4-6disubstituée) ; 760 cm'1 (γ CH phényl 1-2 disubstitué).Infra red spectrum (KBr): 3058 and 3013 cm -1 (aromatic CH); 2934 and 2862 cm -1 (v CH 2), 3000 and 2750 cm -1 (acidic acid), 2800 and 1900 cm -1 (vhfH (amineterium salt + quinoline salt)); C = O acid), 1618, 1600, 1541 and 1497 cm -1 (v C = C aromatic nuclei), 1276 cm -1 (v CO acid), 1251 and 1219 cm -1 (vasC-O ether), 1022 cm -1. 1 (vs C-O ether + n C-0 alcohol), 847 cm -1 (γ CH 4-6 disubstituted quinoline), 760 cm -1 (γ-CH disubstituted 1-2-phenyl).

Spectre de masse (IE - m/z) : 438 (M-CO2)+·; 355 (M-C6H4SF)+; 341 (M-C^SF/picde base ; 297 ; 341 (M-C02)+; 186 (CI2HI2W) ; 128 (C6H5SF+) ; 36 (HC1+.)Mass spectrum (IE - m / z): 438 (M-CO2) + ·; 355 (M-C6H4SF) +; 341 (M-C ^ SF / peak base; 297; 341 (M-CO₂) +; 186 (CI₂H₂W); 128 (C6H5SF +); 36 (HCl +);

Spectre de masse (DCI) ; m/z~t83 (M4-H)+ (3R,4R)-4-[3-(6-irtéthoxyquinolin-4-yl)propyl]-l-[2-(2- fIuoropbéîiyïthio)éthyijpi'péridine-3-carboxylate de méthyleMass spectrum (DCI); m / z-t83 (M4-H) + (3R, 4R) -4- [3- (6-irethoxyquinolin-4-yl) propyl] -1- [2- (2-fluoroporbylthio) ethyl] piperidine-3 methyl carboxylate

En opérant par analogie avec l’exemple 4, mais à partir de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-carboxylate de méthyle et de 2-bromo-l-(2-fluorophénylthio)éthane, on obtient 0,17 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2-fluorophénylthio)éthyl)pipéridine-3-carboxylate de méthyle, sousforme d’une laque de couleur orangée.By analogy with Example 4, but starting from methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate and 2-bromo-1 - (2-fluorophenylthio) ethane, 0.17 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-fluorophenylthio) ethyl) are obtained methyl piperidine-3-carboxylate, in the form of an orange-colored lacquer.

Spectre infra rouge (CH2C12) : 2942 cm'1 nCH aliphatiques ; 1727 cm’1 nC=O ;1227cm'1 n C-O éther ;848 cm'1 gCH quinoline.Infrared spectrum (CH 2 Cl 2): 2942 cm -1 aliphatic nCH; 1727 cm -1 nC = 0; 1227 cm -1 n C-O ether; 848 cm -1 g CH quinoline.

Exemple 12Example 12

Dichlorhydrate de Pacide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(thién-2-ylthio)éthyI]pipéridine-3-carboxylique 120 2 2 190 A une solution agitée de 0,34 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(thièn-2-ylthio)éthyl]pipéridine-3-carboxylate de méthyle dans 3 cm3 de méthanol,on ajoute 0,5 cm3 de soude aqueuse 5N, puis le mélange est chauffé à une températurevoisine de 60°C pendant 20 heures. Après mélange des solvants sous pression réduite(5 kPa), à une température voisine de 40°C, le résidu obtenu est repris par 5 cm3d’eau, puis acidifié par addition de 1 cm3 d’acide chlorhydrique à 35 %. Le mélangeest à nouveau mélangé sous pression réduite dans les mêmes conditions que ci-dessus ; le résidu obtenu est repris par 5 cm3 d’un mélange de dichlorométhane-méthanol (90/10 en volumes). L’insoluble est filtré, puis le solvant est mélangé souspression réduite (5 kPa), à une température voisine de 40°C. On obtient 0,35 g dedichlorhydrate de l’acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(thièn-2-ylthio)éthyl]pipéridine-3-carboxylique, sous forme d’un solide de couleur beigefondant en se ramollissant au voisinage de 150°C.(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-ylthio) ethyl] piperidine-3-carboxylic acid dihydrochloride 120 2 2 190 A a stirred solution of 0.34 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-ylthio) ethyl] piperidine-3 Methyl carboxylate in 3 cm3 of methanol, 0.5 cm3 of 5N aqueous sodium hydroxide is added, and then the mixture is heated to a temperature of 60 ° C for 20 hours. After mixing the solvents under reduced pressure (5 kPa) at a temperature in the region of 40 ° C., the residue obtained is taken up in 5 cm 3 of water and then acidified by addition of 1 cm 3 of 35% hydrochloric acid. The mixture is again mixed under reduced pressure under the same conditions as above; the residue obtained is taken up in 5 cm3 of a mixture of dichloromethane-methanol (90/10 by volume). The insoluble material is filtered and the solvent is then mixed under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 0.35 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-ylthio) ethyl] piperidine acid dihydrochloride is obtained. 3-carboxylic acid, in the form of a beige-colored solid melting in the vicinity of 150 ° C.

Spectre infra rouge (KBr) : 3102 cm'1 (v CH thiophène) ; 3058 et 3012 cm'1 (v CHaromatiques) ; 2932 et 2865 cm'1 (v CH2) ; 3000 et 2750 cm'1 (v OH acide) ; 2800 et1900 cm'1 (v ΝΉ ( sel d’amine tertiaire + sel de quinoline)) ; 1717 cm'1 (v C=Oacide) ; 1618 ;1600 ; 1541 et 1496 cm'1 (v C=C noyaux aromatiques) ; 1276 cm'1 (v C-O acide) ; 1250 et 1218 cm'1 (vas C-O éther) ; 1020 cm'1 (vs C-0 éther + v C-O alcool) ; 846 cm'1 (y CH quinoline 4-6 disubstituée) ; 725 cm'1 (y CH thiophène).Infrared spectrum (KBr): 3102 cm -1 (v thiophene CH); 3058 and 3012 cm -1 (v CH aromatics); 2932 and 2865 cm -1 (v CH 2); 3000 and 2750 cm -1 (acidic OH); 2800 and 1900 cm -1 (v ΝΉ (tertiary amine salt + quinoline salt)); 1717 cm -1 (v C = acid); 1618, 1600; 1541 and 1496 cm -1 (v C = C aromatic rings); 1276 cm -1 (v C-O acid); 1250 and 1218 cm -1 (vC C0 ether); 1020 cm -1 (vs C-O ether + v C-O alcohol); 846 cm -1 CH 4 -quinoline 4-6 disubstituted); 725 cm -1 (thiophene CH).

Spectre de masse (EE - m/z) : 355 (M-C4H3S2)+; 341 (M-CjH5S2)+pic de base ; 297 ;341- M-CO2)+/; 186 (C12HI2NO+) ; 115 (C4H3S2+)Mass Spectrum (EE - m / z): 355 (M-C4H3S2) +; 341 (M-C19H5S2) + base peak; 297; 341-M-CO2) + /; 186 (C12HI2NO +); 115 (C4H3S2 +)

Spectre de masse (DCI) m/z=471 (M+H)+ (3R,4R)-4-[3-(6-méthoxyquinoIin-4-yl)propyI]-l-[2-(thién-2- yIthio)éthyl]pipéridine-3-carboxylate de méthyleMass Spectrum (INI) m / z = 471 (M + H) + (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-one) methyl (ethyl) piperidine-3-carboxylate

En opérant par analogie avec l’exemple 4, mais à partir de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-carboxylate de méthyle et de 2-bromo-l-(thién-2-ylthio)éthane, on obtient 0,34 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(thién-2-ylthio)éthyl] pipéridine-3-carboxylate de méthyle, sousforme d’une laque de couleur verte.By analogy with Example 4, but starting from methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate and 2-bromo-1 - (thien-2-ylthio) ethane, 0.34 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl)) are obtained; methyl ylthio) ethyl] piperidine-3-carboxylate, in the form of a green lacquer.

Spectre de R.M.N. Ή (300 MHz, (CD3)2SO d6, δ en ppm) : de 1,30 à 1,90 (mt : 7H) ;de 2,15 à 2 ,30 (mt : 1 H) ; de 2,35 à 2,60 (mt : 4H) ; de 2,65 à 2,80 (mt : 2H) ; 3,02 (t, J = 7 Hz : 2H) ; 3,03 (t large, J = 7,5 Hz : 2H) ; 3,54 (s : 3H) ; 3,95 (s : 3H) ; 7,06 (dd, J = 5,5 et 3,5 Hz : 1H) ; 7,19 (dd, J = 3,5 et 1,5 Hz : 1H) ; 7,32 (d, J = 4,5 Hz : 1H) ; 1 20 2 21 191 7 ,36 (d, J = 3 Hz : 1H) ; 7,42 (dd, J = 9 et 3 Hz : 1H) ; 7,62 (dd, J = 5,5 et 1,5 Hz :1H) ; 7,95 (d, J = 9 Hz : 1H) ; 8,64 (d, J = 4,5 Hz : 1H).Spectrum of R.M.N. Ή (300 MHz, (CD3) 2SO d6, δ in ppm): from 1.30 to 1.90 (mt: 7H), from 2.15 to 2.30 (mt: 1H); from 2.35 to 2.60 (mt: 4H); from 2.65 to 2.80 (mt: 2H); 3.02 (t, J = 7 Hz: 2H); 3.03 (broad t, J = 7.5 Hz: 2H); 3.54 (s: 3H); 3.95 (s: 3H); 7.06 (dd, J = 5.5 and 3.5 Hz: 1H); 7.19 (dd, J = 3.5 and 1.5 Hz: 1H); 7.32 (d, J = 4.5 Hz: 1H); 1, 2, 191, 191, 36 (d, J = 3 Hz: 1H); 7.42 (dd, J = 9 and 3 Hz: 1H); 7.62 (dd, J = 5.5 and 1.5 Hz: 1H); 7.95 (d, J = 9 Hz: 1H); 8.64 (d, J = 4.5 Hz: 1H).

Exemple 14Example 14

Trichlorhydrate de l’acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(pyridin-2-ylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-ylthio) ethyl] piperidine-3-carboxylic acid trihydrochloride

Une solution de 0,5 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(pyridin-2-ylthio)éthyl]pipéridine-3-carboxylate de méthyle dans 7,8 cm3 d’acidechlorhydrique 6N est chauffée sous agitation à une température voisine de 100°Cpendant 2 heures. Après concentration à sec du mélange réactionnel, sous pressionréduite (5 kPa), à une température voisine de 80°C, le résidu obtenu est trituré dans10 cm3 d’éther diisopropylique. L’insoluble est essoré, puis séché sous pressionréduite (13 kPa), à une température voisine de 60°C. On obtient 0,55 g detrichlorhydrate de l’acide (3R,4R)-4-[3-(6-méthoxyqumolin-4-yl)propyl]-l-[2-(pyridin-2-ylthio)éthyl]pipéridine-3-carboxylique, sous forme d’un solide de couleurcrème, fondant en se ramollissant au voisinage de 165°C.A solution of 0.5 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-ylthio) ethyl] piperidine-3-carboxylate of methyl in 7.8 cm3 of 6N hydrochloric acid is heated with stirring at a temperature of 100 ° C for 2 hours. After concentrating the reaction mixture to dryness under reduced pressure (5 kPa) at a temperature in the region of 80 ° C., the residue obtained is triturated in 10 cm3 of diisopropyl ether. The insoluble material is drained and then dried under reduced pressure (13 kPa) at a temperature in the region of 60 ° C. 0.55 g of (3R, 4R) -4- [3- (6-methoxyquolin-4-yl) propyl] -1- (2- (pyridin-2-ylthio) ethyl] piperidine hydrochloride is obtained. 3-carboxylic acid, in the form of a cream-colored solid, melting and softening at about 165 ° C.

Spectre de R.M.N. 1H (400 MHz, (CD3)2SO d6, δ en ppm) : de 1,20 à 2,40 et de 3,00à 3,60 (mts : 16H) ; 3,62 (t large, J = 7,5 Hz : 2H) ; 4,05 (s : 3H) ; 7,21 (dd, J = 8 et 5Hz : 1H) ; 7,43 (d, J = 8 Hz : 1H) ; 7,67 (s large : 1H) ; 7,73 (t dédoublé, J = 8 et 1,5Hz : 1 H) ; 7,74 (dd, J - 9 et 2,5 Hz : 111) ; 7,95 (d, J - 5 Hz : 1H) ; 8,45 (d, J = 9 Hz :1H) ; 8,49 (d large, J - 5 Hz : 1H) ; 9,05 (d, J- 5 Hz : 1H) ; 11,25 (mf : 1H). (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(pyridin-2-ylthio)éthyl]pipéridine-3-carboxyIate de méthyleSpectrum of R.M.N. 1H (400 MHz, (CD3) 2SO d6, δ in ppm): from 1.20 to 2.40 and from 3.00 to 3.60 (mts: 16H); 3.62 (broad t, J = 7.5 Hz: 2H); 4.05 (s: 3H); 7.21 (dd, J = 8 and 5Hz: 1H); 7.43 (d, J = 8 Hz: 1H); 7.67 (brs: 1H); 7.73 (t split, J = 8 and 1.5Hz: 1H); 7.74 (dd, J-9 and 2.5 Hz: 111); 7.95 (d, J - 5 Hz: 1H); 8.45 (d, J = 9 Hz: 1H); 8.49 (broad d, J - 5 Hz: 1H); 9.05 (d, J-5 Hz: 1H); 11.25 (mf: 1H). Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-ylthio) ethyl] piperidine-3-carboxyIate

En opérant par analogie avec l’exemple 4, mais à partir de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-carboxylate de méthyle et de 2-bromo-l-(pyridin-2-ylthio)éthane, on obtient 0,52 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl)-l-[2-(pyridin-2-ylthio) éthyl]pipéridine-3-carboxylate de méthyle, sousforme d’une huile de couleur jaune.By analogy with Example 4, but starting from methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate and 2-bromo-1 - (pyridin-2-ylthio) ethane gives 0.52 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl) -1- [2- (pyridin-2- methyl (ylthio) ethyl] piperidine-3-carboxylate, in the form of a yellow oil.

Spectre infra rouge (CH2C12) : 2949 cm'1 nCH aliphatiques ; 1737 cm'1 nC=O ;1227cm'1 n C-O éther ;845 cm'1 gCH quinoline. 192 120 2 2Infra red spectrum (CH 2 Cl 2): 2949 cm -1 aliphatic nCH; 1737 cm -1 nC = 0; 1227 cm -1 n C-O ether; 845 cm -1 g CH quinoline. 192 120 2 2

Exemple 15Example 15

Dichlorhydrate de l’acide (3R,4R)-4-[3-(6-méthoxyquinoIin-4-yl)propyl]-l-[2-(cyclohexylthio)-2-éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (6-Methoxyquinyl-4-yl) propyl] -1- [2- (cyclohexylthio) -2-ethyl] piperidine-3-carboxylic acid dihydrochloride

Une solution de 0,55 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(cyclohexylthio)-2-éthyl]pipéridine-3-carboxylate de méthyle dans 8,5 cm3 d’acidechlorhydrique 6N est chauffée sous agitation, à une température voisine de 100°C,pendant 2 heures. Le mélange réactionnel est refroidi, puis concentré à sec souspression réduite (5 kPa), à une température voisine de 80°C. Le résidu obtenu esttrituré dans 15 cm3 d’éther diisopropylique. L’insoluble est filtré, puis le gâteau estlavé par 10 cm3 d’éther diisopropylique. Le solide obtenu est séché sous pressionréduite (13 Pa), à une température voisine de 60°C, pendant 2 heures. On obtient0,51 g dichlorhydrate de l’acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(cyclohexylthio)-2-éthyl]pipéridine-3-carboxylique, sous forme d’un solide decouleur beige, fondant en se ramollissant vers 150°C.A solution of 0.55 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) -2-ethyl] piperidine-3-carboxylate methyl in 8.5 cm3 of 6N hydrochloric acid is heated with stirring at a temperature of 100 ° C for 2 hours. The reaction mixture is cooled and then concentrated to dryness under reduced pressure (5 kPa) at a temperature in the region of 80 ° C. The residue obtained is triturated in 15 cm3 of diisopropyl ether. The insoluble material is filtered and the cake is washed with 10 cm3 of diisopropyl ether. The solid obtained is dried under reduced pressure (13 Pa) at a temperature of 60 ° C for 2 hours. 0.51 g (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) -2-ethyl] piperidine-3-dihydrochloride is obtained carboxylic acid, in the form of a beige-colored solid, melting while softening at about 150 ° C.

Spectre de R.M.N.1H (400 MHz, (CD3)2SO d6, avec ajout de quelques gouttes deCD3COOD d4, à une température de 373K, δ en ppm) : de 1,20 à 2,35 et de 2,75 à 3,50 (mts : 29H) ; 4,03 (s : 3H) ; 7,57 (mt : 1H) ; de 7,60 à 7,75 (mt : 2H) ; 8,24 (d,J = 9Hz: 1H) ; 8,85 (d, J = 5 Hz : 1H). (3R,4R)-4-[3-(6-méthoxyquinoIin-4-yI)propyl]-l-[2-(cycIohexyltliio)-2-éthyl]pipéridine-3-carboxylate de méthyle1 H NMR spectrum (400 MHz, (CD3) 2SO d6, with addition of a few drops ofCD3COOD d4, at a temperature of 373K, δ in ppm): from 1.20 to 2.35 and from 2.75 to 3.50 (mts: 29H); 4.03 (s: 3H); 7.57 (mt: 1H); from 7.60 to 7.75 (mt: 2H); 8.24 (d, J = 9Hz: 1H); 8.85 (d, J = 5 Hz: 1H). Methyl (3R, 4R) -4- [3- (6-methoxyquinyl-4-yl) propyl] -1- [2- (cyclohexylthio) -2-ethyl] piperidine-3-carboxylate

En opérant par analogie avec l’exemple 4, mais à partir de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyi]pipéridine-3-carboxylate de méthyle et de 2-bromo-l-(cyclohexylthio)éthane, on obtient 0,57 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(cyclohexylthio)-2-éthyl]pipéridine-3-carboxylate de méthyle, sousforme d’une huile de couleur orange.By analogy with Example 4, but starting from methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate and 2-bromo-1 ((cyclohexylthio) ethane, 0.57 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) -2-ethyl] piperidine are obtained. Methyl-3-carboxylate, in the form of an orange-colored oil.

Spectre infra rouge (CH-C12) : 2934 cm'1 vCH aliphatiques ; 1732 cm'1 vC=O ; 1227 cm'1 v C-0 éther ;848 cm'1 yCH quinoline.Infrared spectrum (CH-C12): 2934 cm -1 aliphatic vCH; 1732 cm -1 vC = O; 1227 cm -1 C 0 ether, 848 cm -1 quinoline.

Exemple 16Example 16

Di-trifïuoroacétate de l’acide (3R, 4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(2-thiényl)butan-4-one]-pipéridine-3-carboxylique 193 12 0 2 2 A une solution de 1,55 g de di-trifluoroacétate de l’acide (3R, 4R)-4-[3-(6-méthoxy-4-quinolin-4-yl)propyl]-pipéridine-3-carboxylique dans 40 cm3 d’acétone anhydre, onajoute à une température voisine de 20°C, sous agitation et sous atmosphère inerte, 1,76 cm3 de 4-chloro-2’-butyrothiénone, puis 3,86 g de carbonate de potassium. Lemélange est chauffé à une température voisine de 57°C pendant 20 heures. Aprèsrefroidissement du mélange réactionnel, puis filtration de l’insoluble, le gâteau estlavé par 10 cm3 d’acétone, puis le filtrat est mélangé sous pression réduite (5 kPa), àune température voisine de 40°C. Le résidu obtenu est purifié par chromatographie àpression atmosphérique, sur une colonne de gel de silice (granulométrie 20-45 μ ;diamètre 4 cm ; hauteur 35 cm), en éluant par un mélange de dichlorométhane-méthanol (90/10 en volumes), et en recueillant des fractions de 100 cm3. Les fractions43 à 122 sont réunies, puis mélangées sous pression réduite (5 kPa), à unetempérature voisine de 40°C. On obtient 1,09 g d’une huile que l’on soumet à unenouvelle purification par chromatographie à pression atmosphérique sur une colonnede gel de silice (granulométrie 20-45 μ ; diamètre 4 cm ; hauteur 35 cm), en éluant parun mélange de dichlorométhane-méthanol (90/10 en volumes), et en recueillant desfractions de 100 cm3. Les fractions 125 à 216 sont réunies, puis mélangées souspression réduite (5 kPa), à une température voisine de 40°C. On obtient 0,48 g d’unehuile que l’on purifie sous forme de di-trifluoroacétate, préparé- à partir de 0,1 cm3d’acide trifluoroacétique dans un mélange de 10 cm3 de dichlorométhane et 5 cm3 deméthanol. On obtient, après mélange du mélange réactionnel (sous une pressionpartielle de 5 kPa et à une température voisine de 40°C), puis reprise du résidu obtenupar 10 cm3 d’éther diéthylique et filtration du solide, 0,35 g de di-trifluoroacétate del’acide (3R, 4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[4-(2-thiényl) butan-4-one]-pipéridine-3-carboxylique, sous forme d’un solide de couleur beige, à 90 % de pureté.(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (2-thienyl) butan-4-one] -piperidine-3-di (trifluoroacetate) di-trifluoroacetate -carboxylic acid 193 12 0 2 2 To a solution of 1.55 g of (3R, 4R) -4- [3- (6-methoxy-4-quinolin-4-yl) propyl] di-trifluoroacetate piperidine-3-carboxylic acid in 40 cm3 of anhydrous acetone is added at a temperature of 20 ° C, under stirring and under an inert atmosphere, 1.76 cm3 of 4-chloro-2'-butyrothienone, then 3.86 g of potassium carbonate. Lemange is heated to a temperature of 57 ° C for 20 hours. Aftercooling of the reaction mixture, then filtration of the insoluble material, the cake is washed with 10 cm3 of acetone and the filtrate is then mixed under reduced pressure (5 kPa) at a temperature of 40 ° C. The residue obtained is purified by atmospheric pressure chromatography, on a column of silica gel (particle size 20-45 μ, diameter 4 cm, height 35 cm), eluting with a mixture of dichloromethane-methanol (90:10 by volume), and collecting fractions of 100 cm3. Fractions 43 to 122 are combined and then mixed under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 1.09 g of an oil which is subjected to a new purification by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45 μ, diameter 4 cm, height 35 cm), eluting with a mixture of dichloromethane-methanol (90/10 by volume), and collecting fractions of 100 cm3. Fractions 125 to 216 are combined and then mixed under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 0.48 g of an oil is obtained which is purified in the form of di-trifluoroacetate, prepared from 0.1 cm3 of trifluoroacetic acid in a mixture of 10 cm3 of dichloromethane and 5 cm3 of methanol. After mixing the reaction mixture (at a partial pressure of 5 kPa and at a temperature of 40 ° C), then taking the residue obtained with 10 cm3 of diethyl ether and filtration of the solid, 0.35 g of di-trifluoroacetate (3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [4- (2-thienyl) butan-4-one] -piperidine-3-carboxylic acid, under form of a solid beige color, 90% purity.

Spectre de R.M.N. 1H (400 MHz, (CD3)2SO d6, avec ajout de quelques gouttes deCD3COOD d4, à une température de 383K, δ en ppm) : de 1,50 à 2,25 et de 2,95 à3,55 (mts : 20H) ; 3,96 (s : 3H) ; 7,23 (mt : 1H) ; 7,36 (d, J = 5 Hz : 1H) ; de 7,40 à 7,50 (mt : 2H) ; 7,88 (d, J = 4 Hz : 1H) ; 7,92 (d, J = 5 Hz : 1H) ; 7,99 (d, J = 9 Hz :1H); 8,66 (d, J = 5 Hz : 1H). Dî-trifluoroacétate de l’acide (3R, 4R)-4-[3-(6-méthoxyquinolin-4-yl)propyI]-pipéridine-3-carboxylique A une suspension agitée de 1,5 g de l’acide (3R,4R)-l-(/erz-butyloxycarbonyl)-4-[3-(6-methoxy-4-quinolin-4-yl)propyl]-pipéridine-3-carboxylique dans 15 cm3 de 194 120 2 2 dichlorométhane, on ajoute à une température voisine de 20°C, 1,75 cm3 d’acidetrifluoroacétique pur. La solution obtenue est agitée pendant 20 heures à la mêmetempérature, puis mélangée sous pression réduite (5 kPa), à une température voisinede 40°C. On obtient 2,46 g de di-trifluoroacétate de l’acide (2R,4R)-4-[3-(6- 5 méthoxyquinolin-4-yl)propyI]-pipéridine-3-carboxylique, sous forme d’une huile decouleur brune. L’acide (3R, 4R)-1 -(t-butyloxycarbonyl)-4-[3-(6-méthoxyquinolin-4-yl)propyl]- pipéridine-3-carboxylique a été préparé comme dans l’exemple 6.Spectrum of R.M.N. 1H (400 MHz, (CD3) 2SO d6, with addition of a few drops ofCD3COOD d4, at a temperature of 383K, δ in ppm): from 1.50 to 2.25 and from 2.95 to 3.55 (mts: 20H ); 3.96 (s: 3H); 7.23 (mt: 1H); 7.36 (d, J = 5 Hz: 1H); from 7.40 to 7.50 (mt: 2H); 7.88 (d, J = 4 Hz: 1H); 7.92 (d, J = 5 Hz: 1H); 7.99 (d, J = 9 Hz: 1H); 8.66 (d, J = 5 Hz: 1H). (3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -piperidine-3-carboxylic acid trifluoroacetate has a stirred suspension of 1.5 g of (3R) , 4R) -1- (1-eroxybutyloxycarbonyl) -4- [3- (6-methoxy-4-quinolin-4-yl) propyl] -piperidine-3-carboxylic acid in 15 cc of dichloromethane, m.p. add at a temperature of 20 ° C, 1.75 cm3 of pure acid etifluoroacetic acid. The resulting solution is stirred for 20 hours at the same temperature and then mixed under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 2.46 g of (2R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -piperidine-3-carboxylic acid di-trifluoroacetate are obtained in the form of an oil. brown color. (3R, 4R) -1- (t-butyloxycarbonyl) -4- [3- (6-methoxyquinolin-4-yl) propyl] -piperidine-3-carboxylic acid was prepared as in Example 6.

Exemple 19 10 Acide (3R,4R)-4-[3-(6-méthoxyquinoIin-4-yI)propyl]-l-[3-(thièn-3-yl)prop-2-ynyI]pipéridine-3-carboxyliqueExample 19 (3R, 4R) -4- [3- (6-Methoxyquinin-4-yl) propyl] -1- [3- (thien-3-yl) prop-2-yl] piperidine-3-carboxylic acid

Une solution de 0,6 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thièn-3-yl)prop-2-ynyl] pipéridine-3-carboxylate de méthyle dans 10 cm3 de dioxanne estadditionnée de 3,9 cm3 de soude aqueuse IN, puis chauffée à une température voisine 15 de 65°C pendant 16 heures. Le mélange est refroidi puis la phase organique estextraite par 3 fois 50 cm3 d’acétate d’éthyle. La phase aqueuse est acidifiée par 3,9 cm3 d’acide chlorhydrique IN. La solution est reprise par 10 cm3 d’une solutionaqueuse saturée de bicarbonate de sodium puis la phase organique est extraite par2 fois 20 cm3 d’acétate d’éthyle et 2 fois 20 cm3 de dichlorométhane, séchée sur du 20 sulfate de sodium, filtrée et concentrée à sec sous pression réduite (2 kPa), à unetempérature voisine de 45°C. On obtient 0,32 g d’acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyI]-1 -[3-(thièn-3-yl)prop-2-ynyl] pipéridine-3- carboxylique sous forme d’une meringue de couleur blanche.A solution of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop-2-ynyl] piperidine (0.6 g) The methyl 3-carboxylate in 10 cm 3 of dioxane is supplemented with 3.9 cm 3 of 1N aqueous sodium hydroxide and then heated at a temperature in the region of 65 ° C. for 16 hours. The mixture is cooled and the organic phase is extracted with 3 times 50 cm3 of ethyl acetate. The aqueous phase is acidified with 3.9 cm3 of 1N hydrochloric acid. The solution is taken up in 10 cm 3 of a saturated aqueous solution of sodium bicarbonate and then the organic phase is extracted with twice 20 cm 3 of ethyl acetate and 2 times 20 cm 3 of dichloromethane, dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa), at a temperature of about 45 ° C. 0.32 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop-2-ynyl] acid is obtained. piperidine-3-carboxylic acid as a white meringue.

Spectre de R.M.N. ‘H (300 MHz, (CD3)2SO d6, δ en ppm) : de 1,20 à 1,90 (mt : 7H) ; 25 2,43 (mt : 1H) ; de 2,50 à 3,00 (mt : 4H) ; 3,04 (t large, J = 7,5 Hz : 2H) ; 3,55 (s : 2H) ; 3,93 (s : 3H) ; 7,15 (dd, J = 5 et 1,5 Hz : 1H) ; 7,32 (d, J = 5 Hz : 1H) ; de 7,35 à 7,50 (mt : 2H) ; 7,62 (dd, J = 5 et 3 Hz : 1H) ; 7,75 (dd, J = 3 et 1,5 Hz : 1H) ; 7,92 (d, J - 9 Hz : 1H) ; 8,62 (d, J = 5 Hz : 1H) ; de 12,00 à 13,00 (mf très étalé : 1H). (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thièn-3-yl)prop-2-ynyl] 30 pipéridine-3-carboxylate de méthyle »Spectrum of R.M.N. H (300 MHz, (CD3) 2SO d6, δ in ppm): from 1.20 to 1.90 (mt: 7H); 2.43 (mt: 1H); from 2.50 to 3.00 (mt: 4H); 3.04 (broad t, J = 7.5 Hz: 2H); 3.55 (s: 2H); 3.93 (s: 3H); 7.15 (dd, J = 5 and 1.5 Hz: 1H); 7.32 (d, J = 5 Hz: 1H); from 7.35 to 7.50 (mt: 2H); 7.62 (dd, J = 5 and 3 Hz: 1H); 7.75 (dd, J = 3 and 1.5 Hz: 1H); 7.92 (d, J - 9 Hz: 1H); 8.62 (d, J = 5 Hz: 1H); from 12.00 to 13.00 (mf very spread: 1H). Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop-2-ynyl] piperidine-3-carboxylate "

On opère comme à l’exemple 2 à partir de 1 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-yl-prop-2-ynyl] pipéridine>3-carboxylate de méthyle, de 0,9 g de 3- 120 2 2 195 iodothiophène, de 0,2 g de tétrakis(triphénylphosphine)palladium, 0,1 g d’iodurecuivreux, 0,060 g de triphénylphosphine et 0,75 cm3 de triéthy lamine. Le résiduobtenu est purifié par chromatographie à pression atmosphérique sur une colonne degel de silice (granulométrie 40-63 μ ; diamètre 3,5 cm ; hauteur de la colonne 35 cm),en éluant par de l’acétate d’éthyle et en recueillant des fractions de 40 cm3. Lesfractions 18 à 49 sont réunies, puis mélangées sous pression réduite (5 kPa), à unetempérature voisine de 40°C. On obtient 0,6 g de (3R,4R)-4-[3-(6-méthoxyquinolin- 4-yl)propyl]-l-[3-(thièn-3-yl)prop-2-ynyl] pipéridine-3-carboxylate de méthyle sousforme d’une huile brune.The procedure is as in Example 2 starting from 1 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3-yl-prop-2-ynyl] piperidine> methyl 3-carboxylate, 0.9 g of 3-iodothiophene, 0.2 g of tetrakis (triphenylphosphine) palladium, 0.1 g of iodurecubreux, 0.060 g of triphenylphosphine and 0.75 g. cm3 of triethylamine. The residue obtained is purified by chromatography at atmospheric pressure on a silica-thaw column (particle size 40-63 μ, diameter 3.5 cm, column height 35 cm), eluting with ethyl acetate and collecting fractions of 40 cm3. Fractions 18 to 49 are combined and then mixed under reduced pressure (5 kPa) at a temperature of 40 ° C. 0.6 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop-2-ynyl] piperidine are obtained. Methyl 3-carboxylate in the form of a brown oil.

Le 3-iodothiophène peut-être préparé selon N.A. PETASIS et coll., SYNLETT. 1999,141.3-iodothiophene may be prepared according to N.A. PETASIS et al., SYNLETT. 1999.141.

Exemple 21Example 21

Dichlorhydrate de l’acide (3R, 4R)-l-[2-(3-fluorophénylthio)éthyI]-4-[3-(R, S)-hydroxy-3-(6- méthoxyquinolin-4-yl)propyl]-pipéridine-3-carboxylique 0,8 g de (3R, 4R)-l-[2-(3-fluorophénylthio)éthyl]-4-[3-(R, S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyi]-pipéridine-3-carboxylate de méthyle dans 10 cm3 deméthanol et 1,25 cm3 de soude 5N sont chauffés, sous agitation, à une températurevoisine de 60°C pendant 4 heures. Le mélange réactionnel est mélangé sous pressionréduite (5 kPa), à une température voisine de 50°C. Au résidu obtenu, on ajoute15 cm3 d’eau puis on ajoute 2 cm3 d’acide chlorhydrique aqueux 5N. Le mélangeréactionnel est de nouveau mélangé à sec. Le résidu obtenu est trituré avec unmélange de dichlorométhane/méthanol (90/10 en volumes). Le chlorure de sodium estfiltré, puis le filtrat est concentré sous pression réduite (5 kPa), à une températurevoisine de 30°C. La meringue obtenue est triturée avec de l’éther éthylique. Le solideformé est filtré. On obtient 0,75 g de solide beige. Ce solide est dissous dans unmélange de 50 cm3 de chloroforme et de 50 cm3 d’acétonitrile. L’insoluble est filtré,puis le filtrat est acidifié avec 20 cm3 d’éther chlorhydrique IN. Le mélangeréactionnel est mélangé sous pression réduite (5 kPa), à une température voisine de30°C. Le résidu obtenu est trituré avec de l’éther éthylique. Le solide formé est filtrépuis séché sous vide. On obtient 0,7 g de dichlorhydrate de l’acide (3R,4R)-1-(2-(3-fluorophénylthio)éthyl]-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-pipéridine-3-carboxylique, sous forme de solide de couleur beige. 120 2 2 t 196(3R, 4R) -1- [2- (3-Fluorophenylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] dihydrochloride -piperidine-3-carboxylic acid 0.8 g of (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin)) Methyl 4-yl) propyl] -piperidine-3-carboxylate in 10 cm3 of ethanol and 1.25 cm3 of 5N sodium hydroxide are heated, with stirring, to a temperature of 60 ° C for 4 hours. The reaction mixture is mixed under reduced pressure (5 kPa) at a temperature in the region of 50 ° C. To the residue obtained, 15 cm3 of water are added and then 2 cm3 of 5N aqueous hydrochloric acid are added. The reaction mixture is again dry blended. The residue obtained is triturated with a mixture of dichloromethane / methanol (90/10 by volume). Sodium chloride is filtered and the filtrate is concentrated under reduced pressure (5 kPa) at a temperature of about 30 ° C. The meringue obtained is triturated with ethyl ether. The solidformé is filtered. 0.75 g of beige solid is obtained. This solid is dissolved in a mixture of 50 cm3 of chloroform and 50 cm3 of acetonitrile. The insoluble matter is filtered and the filtrate is then acidified with 20 cm 3 of 1N hydrochloric ether. The reaction mixture is mixed under reduced pressure (5 kPa) at a temperature in the region of 30 ° C. The residue obtained is triturated with ethyl ether. The solid formed is filtered and dried under vacuum. 0.7 g of (3R, 4R) -1- (2- (3-fluorophenylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinoline) dihydrochloride is obtained. -4-yl) propyl] -piperidine-3-carboxylic acid as a beige colored solid 120 2 2 t 196

Spectre de R.M.N. (400 MHz, (CD3)2SO d6, δ en ppm) : de 1,25 à 1,90 (mt : 8H) ; 2,22 (mt : 2H) ; de 2,65 à 2,90 (mt : 2H) ; de 3,35 à 3,60 (mt : 4H) ; 3,91 et 3,93 (2s :3H) ; 4,29 (mf : 1H) ; 5,28 (mt : 1H) ; 5,50 et 5,52 (2d, J = 4,5 Hz : 1H) ; 7,07 (mt :1H) ; 7,28 (dd, J = 4 et 1 Hz : 1H) ; de 7,35 à 7,45 (mt : 2H) ; de 7,50 à 7,60 (mt : 5 2H) ; 7,95 (d, J = 9 Hz : 1H) ; 8,71 (d, J = 5 Hz : 1H). (3R,4R)-l-[2-(3-Fluorophénylthio)éthyI]-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoIin-4-yI)propyl]-pipéridine-3-carboxylate de méthyl A une solution de 1,8 g de (3R, 4R)-l-[2-(3-fluorophénylthio)éthyl]-4-[3-(6-méthoxyquinolin-4-yl)-propan-3-one]-pipéridine-3-carboxyIate de méthyle dans 10 20 cm3 de méthanol, on ajoute sous agitation 0,16 g de borohydrure de sodium à une température inférieure à 25 °C. Le mélange réactionnel est agité à la températureambiante pendant 2 heures. Après mélange du méthanol sous pression réduite (5 kPa),le mélange est agité avec 50 cm3 de dichlorométhane et 50 cm3 d’une solution saturéede chlorure d’ammonium. La phase organique est décantée, puis séchée sur sulfate de 15 magnésium. Après filtration sur papier, concentration sous pression réduite (5 kPa), àune température voisine de 40°C, on obtient 1,6 g d’un produit que l’on purifie parchromatographie, à pression atmosphérique, sur une colonne de gel de silice(granulométrie 20-45 μ ; diamètre 3 cm ; 60 g), en éluant par un mélange dedichlorométhane-méthanol (96/4 en volumes), et en recueillant des fractions de 20 10 cm3. On recueille les fractions de 30 à 45. Ces fractions sont réunies, puis concentrées sous pression réduite (5 kPa) à environ 40°C. On obtient 1,05 g de(3R,4R)-l-[2-(3-fluorophénylthio)éthyl]-4-[3-hydroxy-3-(6-méthoxyquinolin-4-yl]-pipéridine-3-carboxylate de méthyle sous forme d’une huile mobile, brune.Spectrum of R.M.N. (400 MHz, (CD3) 2SO d6, δ in ppm): from 1.25 to 1.90 (mt: 8H); 2.22 (mt: 2H); from 2.65 to 2.90 (mt: 2H); from 3.35 to 3.60 (mt: 4H); 3.91 and 3.93 (2s: 3H); 4.29 (mf: 1H); 5.28 (mt: 1H); 5.50 and 5.52 (2d, J = 4.5 Hz: 1H); 7.07 (mt: 1H); 7.28 (dd, J = 4 and 1 Hz: 1H); from 7.35 to 7.45 (mt: 2H); from 7.50 to 7.60 (mt: 5H); 7.95 (d, J = 9 Hz: 1H); 8.71 (d, J = 5 Hz: 1H). (3R, 4R) -l- [2- (3-fluorophenylthio) éthyI] -4- [3- (R, S) -hydroxy-3- (6-méthoxyquinoIin-4-yl) propyl] -piperidin-3- methyl carboxylate To a solution of 1.8 g of (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (6-methoxyquinolin-4-yl) propan-3-one) Methylpiperidine-3-carboxymate in 10 ml of methanol is added with stirring 0.16 g of sodium borohydride at a temperature below 25.degree. The reaction mixture is stirred at room temperature for 2 hours. After mixing the methanol under reduced pressure (5 kPa), the mixture is stirred with 50 cm3 of dichloromethane and 50 cm3 of a saturated solution of ammonium chloride. The organic phase is decanted and then dried over magnesium sulphate. After filtration on paper, concentration under reduced pressure (5 kPa), at a temperature in the region of 40 ° C., 1.6 g of a product which is purified by chromatography at atmospheric pressure on a column of silica gel is obtained. (20-45 micron size, 3 cm diameter, 60 g), eluting with a dichloromethane-methanol mixture (96/4 by volume), and collecting 10 cm3 fractions. Fractions 30 to 45 are collected. These fractions are combined and then concentrated under reduced pressure (5 kPa) at about 40 ° C. 1.05 g of (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) -piperidine-3-carboxylate are obtained. of methyl in the form of a mobile, brown oil.

Le (3R,4R)-l-[2-(3-Fluorophénylthio)éthyl]-4-[3-(6-méthoxyquinolin-4-yl)-propan-3- 25 one]-pipéridine-3-carboxylate de méthyle peut être préparé de la manière suivante :Methyl (3R, 4R) -1- [2- (3-Fluorophenylthio) ethyl] -4- [3- (6-methoxyquinolin-4-yl) propan-3-one] -piperidine-3-carboxylate can be prepared as follows:

Un mélange de 6,44 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)-propan-3-one]-pipéridine-3-carboxylate de méthyle dans 100 cm3 d’acétonitrile, de 3,43 g de 2-(3-fluoro phenylthio)éthyl-1 -chlorure, de 8,85 g de carbonate de potassium et de 1,24 gde l’iodure de potassium est chauffé à une température voisine de 65°C pendant 30 48 heures. Après refroidissement, l’insoluble est filtré. Le filtrat est concentré sous pression réduite (5 kPa), à une température voisine de 40°C. Le résidu huileux estpurifié par chromatographie, à pression atmosphérique, sur une colonne de gel desilice (granulométrie 20-45 μ ; diamètre 6 cm ; 250 g), en éluant par un mélànge de 120 2 2 197 dichlorométhane-acétate d’éthyle-méthanol (50/50/3 en volumes), et en recueillantdes fractions de 50 cm3. On recueille les fractions de 19 à 25. Ces fractions sontréunies, puis concentrées sous pression réduite (5 kPa) à environ 40°C. On obtient2,1 g de (3R,4R)-l-[2-(3-fluorophénylthio)éthyl]-4-[3-(6-méthoxyquinolin-4-yl)propan-3-one]-pipéridine-3-carboxylate de méthyle sous forme d’une huile mobile,brune.A mixture of 6.44 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) -propan-3-one] -piperidine-3-carboxylate in 100 cm3 of acetonitrile, 3.43 g of 2- (3-fluoro-phenylthio) ethyl-1-chloride, 8.85 g of potassium carbonate and 1.24 g of potassium iodide are heated to a temperature in the region of 65 ° C. for 48 hours. After cooling, the insoluble material is filtered. The filtrate is concentrated under reduced pressure (5 kPa) at a temperature of 40 ° C. The oily residue is purified by chromatography, at atmospheric pressure, on a desilicose gel column (particle size 20-45 μ, diameter 6 cm, 250 g), eluting with a mixture of 120 2 2 197 dichloromethane-ethyl acetate-methanol. (50/50/3 by volume), and collecting 50 cm3 fractions. Fractions 19 to 25 were collected. These fractions were combined and concentrated under reduced pressure (5 kPa) at about 40 ° C. 2.1 g of (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (6-methoxyquinolin-4-yl) propan-3-one] -piperidine-3 are obtained methyl carboxylate as a mobile, brown oil.

Le 2-(3-fluorophénylthio)éthyl-l-chlorure peut être obtenu de la manière suivante : A une solution de 10 g de 3-fluorothiophénol, de 0,1 cm3 d’aliquat 336 dans 125 cm3de 1,2-dichloroéthane, on ajoute, goutte à goutte, une solution de 3,75 g de pastille desoude dans 50 cm3 d’eau distillée. La température monte à 33°C. Le mélangeréactionnel est agité à la température ambiante pendant 5 heures. Le mélangeréactionnel est décanté. La phase organique est lavée avec 50 cm3 d’HCl 0,lN, avec50 cm3 d’eau distillée, puis séchée sur sulfate de magnésium. Après filtration surpapier, concentration sous pression réduite (5 kPa), à une température voisine de40°C, on obtient 15 g d’un résidu que l’on purifie par chromatographie, à pressionatmosphérique, sur une colonne de gel de silice (granulométrie 20-45 μ ; diamètre6 cm ; 400 g), en éluant avec du cyclohexane et en recueillant des fractions de100 cm3. On recueille les fractions de 15 à 40. Ces fractions sont réunies, puisconcentrées sous pression réduite (5 kPa) à environ 40°C. On obtient 13,6 g de 2-(3-fluorophényl thio)éthyl-l-chlorure sous forme d’une huile mobile, incolore. (3R,4R)-4-[3-(R,S)“hydroxy-3-(ô~méthoxyquÎnoIin-4-yl)propyIj-l-(3- phénylpropyI)pipéridine-3-carboxylate de méthyle A une solution agitée de 1,59 g de (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]-l-(3-phénylpropyl)pipéridine-3-carboxylate de méthyle dans 25 cm3 deméthanol, on ajoute par petites fractions, à une température voisine de 20°C et sousatmosphère inerte, 0,15 g de borohydrure de sodium. Le mélange est ensuite agitépendant 75 minutes à une température voisine de 20°C. Puis, on ajoute 15 cm3 d’eaudistillée en maintenant la même température^ Le mélange, d’aspect laiteux, estconcentré sous pression réduite (5 kPa), à une température voisine de 30°C. Le résiduobtenu est repris dans 40 cm3 d’eau distillée additionnés de 80 cm3 dedichlorométhane, agité, puis décanté. La phase organique est soutirée, puis lavée parune fois 40 cm3 d’eau, séchée sur sulfate de magnésium. Après filtration sur papier,puis mélange du solvant sous pression réduite (5 kPa), à une température voisine de 198 120 2 2 40°C, on obtient 1,39 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-(3-phénylpropyl)pipéridine-3-carboxylate de méthyle, sous forme d’unsolide d’aspect meringué, et collant, de couleur orange.2- (3-fluorophenylthio) ethyl-1-chloride can be obtained as follows: To a solution of 10 g of 3-fluorothiophenol, 0.1 cm3 of aliquat 336 in 125 cm3 of 1,2-dichloroethane, a solution of 3.75 g of lozenge lozenge in 50 cm3 of distilled water is added dropwise. The temperature rises to 33 ° C. The reaction mixture is stirred at room temperature for 5 hours. The reaction mixture is decanted. The organic phase is washed with 50 cm3 of 0.1N HCl, with 50 cm3 of distilled water, and then dried over magnesium sulfate. After paper filtration, concentration under reduced pressure (5 kPa), at a temperature in the region of 40 ° C., 15 g of a residue are obtained which is purified by chromatography, at atmospheric pressure, on a column of silica gel (granulometry 20 ° C.). -45 μ, diameter 6 cm, 400 g), eluting with cyclohexane and collecting fractions of 100 cm3. Fractions 15 to 40 are collected. These fractions are pooled, concentrated under reduced pressure (5 kPa) at about 40 ° C. 13.6 g of 2- (3-fluorophenylthio) ethyl-1-chloride are obtained in the form of a colorless, mobile oil. Methyl (3R, 4R) -4- [3- (R, S) -) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-3-carboxylate To a stirred solution 1.59 g of methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-3-carboxylate in 25 cm3 methanol, 0.15 g of sodium borohydride are added in small portions, at a temperature in the region of 20.degree. C. and an inert subatmosphere. The mixture is then stirred for 75 minutes at a temperature in the region of 20 ° C. Then, 15 cm3 of water-distilled water is added while maintaining the same temperature. The mixture, of milky appearance, is concentrated under reduced pressure (5 kPa) at a temperature in the region of 30 ° C. The residue obtained is taken up in 40 cm3 of distilled water and treated with 80 cm 3 of dichloromethane, stirred and decanted. The organic phase is withdrawn and then washed once with 40 cm3 of water, dried over magnesium sulfate. After filtration on paper, and then mixing the solvent under reduced pressure (5 kPa), at a temperature in the region of 198 120 2 40 ° C., 1.39 g of (3R, 4R) -4- [3- (R) are obtained. Methyl (S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-3-carboxylate, in the form of a meringue-type, sticky, colorless solid orange.

Le (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(3-phénylpropyl) pipéridine-3-carboxylate de méthyle peut être préparé de la manière suivante :Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-3-carboxylate can be prepared in the following manner:

Une suspension de 4,51 g de (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-carboxylate de méthyle et de 2,3 g de carbonate de potassium dans75 cm3 d’acétone est chauffée sous agitation à une température voisine de 58°C. Acette température, on ajoute goutte à goutte une solution de 2,5 cm3 de l-bromo-3-phénylpropane dans 7,5 cm3 d’acétone. Le chauffage est prolongé pendant 19 heures.Après refroidissement, la masse réactionnelle est filtrée ; le gâteau est lavé par 2 fois30 cm3 d’acétone. Le filtrat et les eaux de lavage sont réunis, concentrés sous pressionréduite (5 kPa), à une température voisine de 30°C. On obtient 7,12 g d’un produitsous forme d’huile que l’on purifie par chromatographie à pression atmosphérique surune colonne de gel de silice (granulométrie 20-45 μ ; diamètre 7 cm ; masse 712 g),en éluant par un mélange chloroforme-méthanol-ammoniaque (12/2,25/0,38 envolumes), et en recueillant des fractions de 65 cm3. Les fractions 9 à 14 sont réunies,puis concentrées sous pression réduite (5 kPa), à une température voisine de 30°C. Onobtient 6,7 g d’une huile que l’on soumet à une seconde purification parchromatographie à pression atmosphérique sur colonne de gel de silice (granulométrie20-45 μ ; diamètre 4,8 cm ; masse 336 g), en éluant par un mélange d’acétate d’éthyleet de méthanol (9/1 en volumes), et en recueillant des fractions de 20 cm3. Lesfractions 71 à 122 sont réunies puis concentrées sous pression réduite (5 kPa), à unetempérature voisine de 30°C. On obtient 1,66 g de (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(3-phénylpropyl)pipéridine-3-carboxylate de méthyle, sous forme d’une huile de couleur brune.A suspension of 4.51 g of methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate and 2.3 g of potassium in 75 cm3 of acetone is heated with stirring at a temperature of 58 ° C. At this temperature, a solution of 2.5 cm 3 of 1-bromo-3-phenylpropane in 7.5 cm 3 of acetone is added dropwise. Heating is continued for 19 hours. After cooling, the reaction mass is filtered; the cake is washed with twice 30 cm3 of acetone. The filtrate and the washings are combined and concentrated under reduced pressure (5 kPa) at a temperature in the region of 30 ° C. 7.12 g of a product in the form of an oil are obtained which is purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45 μ, diameter 7 cm, mass 712 g), eluting with a chloroform-methanol-ammonia mixture (12 / 2.25 / 0.38 volumes), and collecting fractions of 65 cm3. Fractions 9 to 14 are combined and then concentrated under reduced pressure (5 kPa) at a temperature in the region of 30 ° C. 6.7 g of an oil which is subjected to a second purification parchromatography at atmospheric pressure on a column of silica gel (particle size 20-45 μ, diameter 4.8 cm, mass 336 g) are obtained, eluting with a mixture ethyl acetate and methanol (9/1 by volume), and collecting fractions of 20 cm3. Fractions 71 to 122 are combined and then concentrated under reduced pressure (5 kPa), at a temperature of 30 ° C. 1.66 g of methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-3-carboxylate are obtained. form of a brown oil.

Le (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyljpipéridine-3-carboxylate deméthyle peut être préparé de la manière suivante :(3R, 4R) -4- [3-Oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylic acid methyl ester can be prepared in the following manner:

Une solution de 19,4 g d’acide (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propylj-l-(t-butyloxocarbonyl)pipéridine-3-carboxylique (teneur à 80 %) dans 355 cm3 deméthanol est refroidie à une température voisine de -30°C. On ajoute sous agitation7,7 cm3 de chlorure de thionyle en maintenant la température entre -25 et -30°C.Après l’addition, on maintient le mélange aux environs de -30°C pendant 30 minutes, 120 2 2 199 puis on laisse revenir la température aux environs de 20°C. Après agitation àtempérature ambiante pendant 19 heures, le mélange réactionnel est concentré souspression réduite (5 kPa), à une température voisine de 30°C. Le résidu obtenu estrepris par 300 cm3 d’eau additionnés de 200 cm3 de dichlorométhane, puis agité. Laphase organique est décantée ; la phase aqueuse est à nouveau extraite par 200 cm3 dedichlorométhane. La solution aqueuse est amenée à pH 8 par addition progressived’hydrogénocarbonate de sodium solide. Après extraction de la solution alcalineobtenue par 3 fois 200 cm3 de dichlorométhane, les extraits organiques réunis sontlavés par 2 fois 200 cm3 d’eau, puis séchés sur sulfate de magnésium. Après filtrationsur papier, la solution organique est concentrée sous pression réduite (5 kPa), à unetempérature voisine de 40°C. On obtient 4,51 g de (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-carboxylate de méthyle .sous forme d’unelaque de couleur brune. L’acide (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]-l-(tert-butOxy- carbonyl)pipéridine-3-carboxylique peut être préparé de la manière suivante :A solution of 19.4 g of (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (t-butyloxocarbonyl) piperidine-3-carboxylic acid (content 80%) in 355 cm3 of ethanol is cooled to a temperature of -30 ° C. 7.7 cc of thionyl chloride are added while stirring, maintaining the temperature between -25 and -30 ° C. After the addition, the mixture is maintained at about -30 ° C. for 30 minutes, then 120-2.2199. let the temperature return to around 20 ° C. After stirring at room temperature for 19 hours, the reaction mixture is concentrated under reduced pressure (5 kPa) at a temperature of 30 ° C. The residue obtained is taken with 300 cm3 of water added with 200 cm3 of dichloromethane and stirred. Organic Laphase is decanted; the aqueous phase is again extracted with 200 cm3 of dichloromethane. The aqueous solution is brought to pH 8 by the progressive addition of solid sodium hydrogencarbonate. After extraction of the alkaline solution obtained with 3 times 200 cm3 of dichloromethane, the combined organic extracts are washed twice with 200 cm3 of water and then dried over magnesium sulfate. After paper filtrations, the organic solution is concentrated under reduced pressure (5 kPa) at a temperature of 40 ° C. 4.51 g of methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate are obtained in the form of a brown-colored fiber. (3R, 4R) -4- [3-Oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (tert-butoxycarbonyl) piperidine-3-carboxylic acid can be prepared in the manner next :

Une solution de 36 g de (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]-3-vinylpipéridine dans 54 cm3 d’acétone est refroidie à une température voisine de 0°C.On ajoute en 15 minutes, sous agitation, 150 cm3 d’acide sulfurique 3 M, enmaintenant la température entre 0 et 5°C. On abaisse la température au voisinage de0°C et l’on ajoute goutte à goutte au mélange une solution de 32 g de permanganatede sodium dans 200 cm3 d’eau distillée. Le mélange réactionnel est agité 45 minutessupplémentaires à une température comprise entre 10 et 15°C, puis on laisse remonterla température au voisinage de 20°C. Après agitation 3 heures à cette température, lamasse réactionnelle est refroidie à une température voisine de 0°C, puis on ajoutelentement 160 cm3 de lessive de potasse à 38 % à une température inférieure à 10°C.Après 30 minutes d’agitation à une température voisine de 10°C, le mélange est filtré.Le gâteau est repris dans 300 cm3 d’eau additionnés de 15 cm3 de lessive de potasse à38 %, et agité pendant 20 minutes. Après filtration, puis lavage du gâteau par 2 fois200 cm3 d’eau distillée, les filtrats sont réunis puis additionnés de 24 g dedi-tertiobutyldicarbonate. La solution est agitée à une température voisine de 20°Cpendant 15 heures. Après addition d’un litre d’acétate d’éthyle, et agitation, lemélange est décanté, la phase aqueuse séparée puis amenée à pH 5 par addition de38 cm3 d’acide chlorhydrique aqueux concentré à 37 %. Le mélange est extrait ànouveau par 5 fois 1 litre d’acétate d’éthyle. Les extraits sont réunis puis lavés par2 fois 1 litre d’eau saturée en chlorure de sodium. La solution organique est séchée 200 120 2 2 sur sulfate de magnésium, filtrée sur papier, concentrée sous pression réduite (5 kPa),à une température voisine de 40°C. On obtient 21,2 g d’acide (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]-l-(t-butyloxycarbonyl)pipéridine-3-carboxylique, sousforme d’un solide brun fondant à 114°C en devenant pâteux. 5 La (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]-3-vinylpipéridine peut êtreobtenue par application de la méthode décrite dans la demande de brevet FR 2354771.A solution of 36 g of (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -3-vinylpiperidine in 54 cm3 of acetone is cooled to a temperature of about 0.degree. C. In 150 minutes of stirring, 150 cc of 3 M sulfuric acid are added, keeping the temperature between 0 and 5 ° C. The temperature is lowered to about 0 ° C and a solution of 32 g of sodium permanganate in 200 cm3 of distilled water is added dropwise to the mixture. The reaction mixture is stirred an additional 45 minutes at a temperature between 10 and 15 ° C, then the temperature is allowed to rise to around 20 ° C. After stirring for 3 hours at this temperature, the reaction mass is cooled to a temperature in the region of 0 ° C., and then 160 cm 3 of potassium hydroxide solution are added at 38% at a temperature of less than 10 ° C. After stirring for 30 minutes at a temperature of temperature around 10 ° C, the mixture is filtered.The cake is taken up in 300 cm3 of water with 15 cm3 of potassium hydroxide solution at 38%, and stirred for 20 minutes. After filtration, then washing the cake with 2 times 200 cm3 of distilled water, the filtrates are combined and then added 24 g of di-tert-butyl dicarbonate. The solution is stirred at a temperature of 20 ° C for 15 hours. After addition of one liter of ethyl acetate and stirring, the mixture is decanted, the aqueous phase separated and brought to pH 5 by addition of 38 cm3 of 37% concentrated aqueous hydrochloric acid. The mixture is extracted again with 5 times 1 liter of ethyl acetate. The extracts are combined and then washed twice with 1 liter of water saturated with sodium chloride. The organic solution is dried over magnesium sulfate, filtered on paper and concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 21.2 g of (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (t-butyloxycarbonyl) piperidine-3-carboxylic acid are obtained. a brown solid melting at 114 ° C becoming pasty. (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -3-vinylpiperidine can be obtained by applying the method described in patent application FR 2354771.

Exemple 22Example 22

Dichlorhydrate de l’acide (3R, 4R)-l-[2-(3-fluorophénylthio)éthyI]-4-[3-(R, S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-pipéridine-3-carboxylique 10 0,9 g de (3R, 4R)-l-[2-(3-fluorophénylthio)éthyl]-4-[3-(R, S)-fluoro-3-(6- méthoxyquinolin-4-yl)propyl]-pipéridine-3-carboxylate de méthyle dans 12 cm3 deméthanol et 1,4 cm3 de soude 5N sont chauffés, sous agitation, à une températurevoisine de 60°C pendant 4 heures. Le mélange réactionnel est mélangé sous pressionréduite (5 kPa), à une température voisine de 50°C. Au résidu obtenu, on ajoute 15 15 cm3 d’eau puis on ajoute 2,1 cm3 d’acide chlorhydrique aqueux 5N. Le mélange réactionnel est de nouveau mélangé à sec. Le résidu obtenu est repris avec un mélangede dichlorométhane/méthanol (90/10 en volumes). Le chlorure de sodium est filtré,puis le filtrat est concentré sous pression réduite (5 kPa), à une température voisine de30°C. La meringue obtenue est triturée avec de l’éther éthylique. Le solide formé est 20 filtré. On obtient 0,9 g de solide beige. Ce solide est dissous dans un mélange de50 cm3 de chloroforme et de 50 cm3 d’acétonitrile. L’insoluble est filtré, puis le filtratest acidifié avec 20 cm3 d’éther chlorhydrique IN. Le mélange réactionnel estmélangé sous pression réduite (5 kPa), à une température voisine de 30°C. Le résiduobtenu est trituré avec de l’éther éthylique. Le solide formé est filtré puis séché sous 25 vide. On obtient 0,9 g de dichlorhydrate de l’acide (3R,4R)-l-[2-(3-fluorophénylthio)éthyl]-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-pipéridine-3-carboxylique, sous forme de solide de couleur beige.(3R, 4R) -1- [2- (3-Fluorophenylthio) ethyl] -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] dihydrochloride dihydrochloride 3-Piperidine-3-carboxylic acid 0.9 (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin) Methyl 4-yl) propyl] -piperidine-3-carboxylate in 12 cm3 of ethanol and 1.4 cm3 of 5N sodium hydroxide are heated, with stirring, to a temperature of 60 ° C for 4 hours. The reaction mixture is mixed under reduced pressure (5 kPa) at a temperature in the region of 50 ° C. To the residue obtained, 15 cm3 of water are added and then 2.1 cm3 of 5N aqueous hydrochloric acid are added. The reaction mixture is again mixed dry. The residue obtained is taken up with a mixture of dichloromethane / methanol (90/10 by volume). The sodium chloride is filtered and the filtrate is concentrated under reduced pressure (5 kPa) at a temperature of 30 ° C. The meringue obtained is triturated with ethyl ether. The solid formed is filtered. 0.9 g of beige solid are obtained. This solid is dissolved in a mixture of 50 cm3 of chloroform and 50 cm3 of acetonitrile. The insoluble matter is filtered and the filtrate is acidified with 20 cm 3 of 1N hydrochloric ether. The reaction mixture is mixed under reduced pressure (5 kPa) at a temperature in the region of 30 ° C. The residue obtained is triturated with ethyl ether. The solid formed is filtered and dried under vacuum. 0.9 g of (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin) dihydrochloride salt are obtained. 4-yl) propyl] -piperidine-3-carboxylic acid, as a beige solid.

Spectre de R.M.N. ^H (600 MHz, (CD3)2SO d6 avec ajout de quelques gouttes deCD3COOD d4, à une température de 383K, δ en ppm) : de 1,40 à 2,25 et de 2,65 à 30 3,65 (mts : 16H) ; 3,96 (s : 3H) ; 6,31 (ntt, JHF = 47 Hz : 1H) ; 7,03 (mt : 1H) ; 7,25 (mt : 2H) ; de 7,30 à 7,45 (mt : 2H) ; 7,53 (mt : 1H) ; 7,57 (mt : 1H) ; 8,09 (d, J = 9Hz : 1H) ; 8,82 (d, J = 5 Hz : 1H). 12 0 2 2 201 (3R,4R)-l-[2-(3-FluorophényIthio)éthyl]-4-[3-(R,S)-fluoro-3-(6-méthoxyquinoIin- 4-yl)propyl]-pipéridine-3-carboxylate de méthyle 1,7 g de (3R, 4R)-l-[2-(3-fluorophénylthio)éthyl]-4-[3-(R, S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-pipéridine-3-carboxylate de méthyle sont dissous dans17 cm3 de aichlorométh&amp;ne, sous atmosphère d’argon. On ajoute, goutte à goutte, sousagitation à 20°C, 0,53 cm3 de diéthylaminosulfure trifluorure. Après 2 heuresd’agitation à la température ambiante, le mélange réactionnel est refroidi à 15°C, puis20 cm3 d’une solution saturée d’hydrogénocarbonate de sodium sont ajoutés goutte àgoutte. La phase organique est décantée, puis la phase aqueuse est extraite 2 fois par50 cm3 de dichlorométhane. Les extraits organiques réunis sont lavés par 2 fois50 cm3 d’eau distillée, puis séchés sur sulfate de magnésium. Après filtration surpapier, la solution est mélangée sous pression réduite (5 kPa) à une températurevoisine de 30°C. On obtient 1,6 g d’une huile brune que l’on purifie en deux fois parchromatographie à pression atmosphérique sur une colonne de gel de silice(granulométrie 20-45 μ ; diamètre 3 cm ; 60 g), en éluant par un mélange dedichlorométhane/m éthanol (98/2 en volumes) et en recueillant des fractions de10 cm3. Pour la première fois, on recueille les fractions de 15 à 25. Pour la secondefois, on recueille les fractions de 18 à 30. Ces fractions sont réunies, puis concentréessous pression réduite (5 kPa). On obtient 0,92 g de (3R,4R)-l-[2-(3-fluorophénylthio)éthyI]-4-[3-(R,S)-fiuoiO-3-(6-méthoxyqumolin-4-yî)propyl]-pipéridine-3-carboxylate de méthyle, sous forme d’une huile brune.Spectrum of R.M.N. ^ H (600 MHz, (CD3) 2SO d6 with addition of a few drops ofCD3COOD d4, at a temperature of 383K, δ in ppm): from 1.40 to 2.25 and from 2.65 to 3.65 (mts : 16H); 3.96 (s: 3H); 6.31 (nt, JHF = 47 Hz: 1H); 7.03 (mt: 1H); 7.25 (mt: 2H); from 7.30 to 7.45 (mt: 2H); 7.53 (mt: 1H); 7.57 (mt: 1H); 8.09 (d, J = 9Hz: 1H); 8.82 (d, J = 5 Hz: 1H). 201 (3R, 4R) -1- [2- (3-Fluorophenylthio) ethyl] -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] Methylpiperidine-3-carboxylate 1.7 g of (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6- methyl methoxyquinolin-4-yl) propyl] -piperidine-3-carboxylate are dissolved in 17 cm3 of aichlorometh &amp;, under argon atmosphere. 0.53 cm3 of diethylaminosulphide trifluoride are added dropwise to the mixture at 20 ° C. After stirring for 2 hours at room temperature, the reaction mixture is cooled to 15 ° C., then 20 cm3 of a saturated solution of sodium hydrogencarbonate are added dropwise. The organic phase is decanted, then the aqueous phase is extracted twice with 50 cm3 of dichloromethane. The combined organic extracts are washed with twice 50 cm3 of distilled water and then dried over magnesium sulfate. After filtration on paper, the solution is mixed under reduced pressure (5 kPa) at a temperature of 30 ° C. 1.6 g of a brown oil which is purified in two times by chromatography at atmospheric pressure on a column of silica gel (granulometry 20-45 μ, diameter 3 cm, 60 g), eluting with a mixture of dichloromethane / methanol (98/2 by volume) and collecting 10 cm3 fractions. For the first time, the fractions of 15 to 25 are collected. For the second time, fractions of 18 to 30 are collected. These fractions are combined and then concentrated under reduced pressure (5 kPa). 0.92 g of (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (R, S) -IOOO-3- (6-methoxyqumolin-4-yl) are obtained. methyl propyl] -piperidine-3-carboxylate, in the form of a brown oil.

Le (3R,4R)-l-[2-(3-fluorophénylthio)éthyl3-4-[3-(R,S)-hydroxy-3-(6-méthoxy quinolin-4-yl) propyl]-pipéridine-3-carboxylate de méthyle est obtenu comme décrit àl’exemple 21.(3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -piperidine-3 Methyl carboxylate is obtained as described in Example 21.

Exemple 23Example 23

Dichlorhydrate de l’acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yI)propyl]-l-[2-(l3_tl1iazol-2-ylthio)éthyl]pipéridme-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (13-triazol-2-ylthio) dihydrochloride) ethyl] pipéridme-3-carboxylic acid

Un mélange de 0,21 g de (3R,4R)-4-[3(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-l-[2-(l,3-thiazol-2-ylthio)éthyl] pipéridine-3-carboxylate de méthyle, et de0,33 cm3 de soude aqueuse 5N dans 3 cm3 de méthanol est chauffé à une températurevoisine de 60°C, sous agitation, pendant 18 heures. Après refroidissement, le mélangeréactionnel est mélangé sous pression réduite (5 kPa), à une température voisine de40°C ; le résidu est repris dans 6 cm3 d’eau, puis lavé avec 6 cm3 d’acétate d’éthyle. 202 120 2 2A mixture of 0.21 g of (3R, 4R) -4- [3 (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1, 3 Methyl thiazol-2-ylthio) ethyl] piperidine-3-carboxylate, and 0.33 cm3 of 5N aqueous sodium hydroxide in 3 cm3 of methanol is heated to a temperature of 60 ° C with stirring for 18 hours. After cooling, the reaction mixture is mixed under reduced pressure (5 kPa), at a temperature of 40 ° C; the residue is taken up in 6 cm3 of water and then washed with 6 cm3 of ethyl acetate. 202 120 2 2

La phase aqueuse est mélangée à sec sous pression réduite (5 kPa), à une températurevoisine de 80°C. Le résidu obtenu est trituré dans 5 cm3 de dichlorométhane, puisacidifié par addition de 1 cm3 d’éther diisopropylique chlorhydrique 3,3 N.L’insoluble est filtré, lavé par 2 fois 3 cm3 d’un mélange de dichlorométhane-méthanol (90/10 en volumes). Le filtrat est mélangé sous pression réduite (5 kPa), àune température voisine de 40°C. On obtient 0,19 g de dichlorhydrate de l’acide(3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(l,3-thiazol-2-ylthio) éthyI]pipéridine-3-carboxylique, sous forme d’un solide amorphe de couleurbeige, fondant vers 75°C en devenant pâteux.The aqueous phase is dry mixed under reduced pressure (5 kPa) at a temperature of about 80 ° C. The residue obtained is triturated in 5 cm3 of dichloromethane, then acidified by addition of 1 cm3 of 3.3 N hydrochloric diisopropyl ether. The insoluble material is filtered, washed with twice 3 cm3 of a mixture of dichloromethane-methanol (90 / 10 in volumes). The filtrate is mixed under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 0.19 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2R) -2-dihydrochloride salt are obtained. (1,3-Thiazol-2-ylthio) ethyl] piperidine-3-carboxylic acid, in the form of an amorphous solid of beige color, melting at about 75 ° C., becoming pasty.

Spectre de R.M.N. (400 MHz, (CD3)2SO d6 avec ajout de quelques gouttes deCDjCOOD d4, à une température de 373K, δ en ppm) : de 1,35 à 2,15 et de 2,50 à3,70 (mt : 16H) ; 3,94 (s : 3H) ; 5,28 (mt : 1H) ; de 7,40 à 7,75 (mt : 5H) ; 7,99 (d,J = 9 Hz : 1H) ; 8,72 (d, J = 5 Hz : 1H). (3R,4R)- 4-[3-(R,S)-Hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(l,3- thiazol-2-ylthio) éthyl] pipéridine-3-carboxylate de méthyleSpectrum of R.M.N. (400 MHz, (CD3) 2SO d6 with addition of a few drops ofCDjCOOD d4, at a temperature of 373K, δ in ppm): from 1.35 to 2.15 and from 2.50 to 3.70 (mt: 16H); 3.94 (s: 3H); 5.28 (mt: 1H); from 7.40 to 7.75 (mt: 5H); 7.99 (d, J = 9 Hz: 1H); 8.72 (d, J = 5 Hz: 1H). (3R, 4R) - 4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1,3-thiazol-2-ylthio) ethyl) ] methyl piperidine-3-carboxylate

En opérant par analogie avec l’exemple 21, mais à partir de (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(l,3-thiazol-2-ylthio)éthyl]pipéridine-3-carboxylate de méthyle et de borohydrure de sodium, on obtient 0,17 g de (3R,4R)-4-[3(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(l,3-thiazol-2-ylthio)éthyl]pipéridine-3-carboxylate de méthyle, sous forme d’une huile visqueuse de couleurjaune.By analogy with Example 21, but starting from (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1, 3 Methyl-thiazol-2-ylthio) ethyl] piperidine-3-carboxylate and sodium borohydride give 0.17 g of (3R, 4R) -4- [3 (R, S) -hydroxy-3- ( Methyl 6-methoxyquinolin-4-yl) propyl] -1- [2- (1,3-thiazol-2-ylthio) ethyl] piperidine-3-carboxylate as a viscous yellow-colored oil.

Spectre infra rouge (CC14) : 3550-3150 cm'1 v OH alcool; 2949 cm'1 vCHaliphatiques ; 1736 cm'1 vC=O;1228 cm'1 v C-0 éther ; 103 lcm'1 v C-O alcool;854 cm'1 yCH quinoline.Infrared spectrum (CCl4): 3550-3150 cm -1 alcohol; 2949 cm -1 Caliphatic; 1736 cm -1 C = 0; 1228 cm -1 C 0 ether; 103 lcm'1 v C-O alcohol; 854 cm'1 yCH quinoline.

Le (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(l,3-thiazol-2-ylthio)éthyl]pipéridine-3-carboxylate de méthyle peut être préparé par analogie avecl’exemple 4, à partir de (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-carboxylate de méthyle et de 2-(2-chloro-éthylthio)-thiazole.(3R, 4R) -4- [3-Oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1,3-thiazol-2-ylthio) ethyl] piperidine-3 Methyl carboxylate can be prepared by analogy with Example 4, from methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate and 2- (2-chloro-ethylthio) -thiazole.

Le 2-(2-chloro-éthylthio)-thiazole peut être préparé de la manière suivante :2- (2-Chloroethylthio) thiazole can be prepared in the following manner:

Dans une solution agitée de 1,47 g de 2-mercaptothiazole et de 1,95 g de carbonate depotassium dans 12,5 cm3 de diméthylformamide, on coule à une température voisine 120 2 2 203 de 20°C, 1,2 cm3 de l-bromo-2-chloroéthane. Le mélange est ensuite agité pendant2 heures à une température voisine de 20°C. L’insoluble est filtré, lavé par 2 fois5 cm3 de diméthylformamide. Le filtrat est coulé sur un mélange de 50 g de glacepilée et 50 cm3 d’eau distillée, puis on ajoute 50 cm3 d’éther éthylique, le mélange estagité, puis décanté. La phase aqueuse est décantée, puis extraite par 2 fois 25 cm3d’éther éthylique. Les phases éthérées réunies, sont lavées par 2 fois 25 cm3 d’eau,puis séchées sur sulfate de magnésium. Après filtration sur papier, la solutionorganique est mélangée sous pression réduite (5 kPa), à une température voisine de40°C. On obtient 2,11 g de 2-(2-chloro-éthylthio)-thiazole, sous forme d’une huilemobile de couleur jaune.In a stirred solution of 1.47 g of 2-mercaptothiazole and 1.95 g of potassium carbonate in 12.5 cm 3 of dimethylformamide, a temperature of 20 ° C, 1.2 cm 3 l-bromo-2-chloroethane. The mixture is then stirred for 2 hours at a temperature in the region of 20 ° C. The insoluble material is filtered and washed twice with 5 cm3 of dimethylformamide. The filtrate is poured onto a mixture of 50 g of ice-cream and 50 cm 3 of distilled water, then 50 cm 3 of ethyl ether are added, the mixture is stirred and then decanted. The aqueous phase is decanted and then extracted with twice 25 cm3 of ethyl ether. The combined ethereal phases are washed with twice 25 cm3 of water and then dried over magnesium sulfate. After filtration on paper, the organic solution is mixed under reduced pressure (5 kPa) at a temperature of 40 ° C. 2.11 g of 2- (2-chloroethylthio) thiazole is obtained in the form of a yellow oil.

Exemple 24Example 24

Dichlorhydrate de l’acide (3R,4R)- 4-[3-(R,S)-hydroxy 3-(6-méthoxyquinolin-4~yl)propyl]-l-[2-(2-thiénylthio)éthyl] pipéridine-3-carboxylique(3R, 4R) - 4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine dihydrochloride -3-carboxylic acid

Un mélange de 0,45 g de (3R,4R)- 4-[3-(R,S)-hydroxy 3-(6-méthoxyquinolin-4-yl)propyî]-l-[2-(2-thiényllthio)éthyi] pipéridine-3-carboxylate de méthyle, 3,5 cm3 deméthanol, et 0,54 cm3 de soude aqueuse 5N est chauffé sous agitation à unetempérature voisine de 60°C pendant 20 heures. Après mélange des solvants souspression réduite (5 kPa), à une température voisine de 40°C, le résidu obtenu estrepris dans 3 cm3 d’une solution aqueuse 6N d’acide chlorhydrique. La solution estmélangée dans les mêmes conditions, puis le résidu obtenu est trituré dans unmélange de dichlorométhane-méthanol (90/10 en volumes). L’insoluble est filtré, lavé2 fois par 1 cm3 de ce mélange. Le filtrat est séché sur sulfate de sodium, puisconcentré sous pression réduite (5 kPa), à une température voisine de 40°C. Aprèsséchage à l’air, on obtient 0,16 g de dichlorhydrate de l’acide (3R,4R)-4-[3-(R,S)-hydroxy 3-(6-méthoxyquinolin-4-yl)propyl]- l-[2-(2-thiényllthio)éthyl] pipéridine-3-carboxylique, sous la forme d’un solide beige fondant, en se ramollissant, vers 148°C.A mixture of 0.45 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (2- (2-thienyllthio) Methyl ethyl piperidine-3-carboxylate, 3.5 cm3 of ethanol, and 0.54 cm3 of 5N aqueous sodium hydroxide is heated with stirring at a temperature of 60 ° C for 20 hours. After mixing the solvents under reduced pressure (5 kPa) at a temperature in the region of 40 ° C., the residue obtained is taken up in 3 cm 3 of a 6N aqueous solution of hydrochloric acid. The solution is mixed under the same conditions, and the residue obtained is triturated in a mixture of dichloromethane-methanol (90/10 by volume). The insoluble material is filtered and washed 2 times with 1 cm 3 of this mixture. The filtrate is dried over sodium sulphate and concentrated under reduced pressure (5 kPa) at a temperature in the region of 40.degree. After drying in air, 0.16 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] dihydrochloride is obtained. 1- [2- (2-Thienyllthio) ethyl] piperidine-3-carboxylic acid, as a melting beige solid, softening at about 148 ° C.

Spectre de R.M.N. (300 MHz, (CD3)2SO d6 avec ajout de quelques gouttes deCDjCOOD d4, δ en ppm) : de 1,35 à 2,30 et de 2,80 à 3,75 (mts : 16H) ; 3,98 et 4,00(2s : 3H) ; de 5,40 à 5,63 (mt : 1H) ; de 7,05 à 7,15 (mt : 1H) ; de 7,25 à 7,40 (mt :1H) ; de 7,50 à 7,80 (mt : 3H) ; 8,00 (mt : 1H) ; 8,24 (d large, J = 9 Hz : 1H) ; 9,05 (d,J = 5 Hz : 1H). (3R,4R)- 4-[3-(R,S)-hydroxy 3-(6-méthoxyquinolin-4-yl)propyI]-l-[2-(2-thiénylthiojéthyl] pipéridine-3-carboxylate de méthyle 204 120 2 2Spectrum of R.M.N. (300 MHz, (CD3) 2SO d6 with addition of a few drops ofCDjCOOD d4, δ in ppm): from 1.35 to 2.30 and from 2.80 to 3.75 (mts: 16H); 3.98 and 4.00 (2s: 3H); from 5.40 to 5.63 (mt: 1H); from 7.05 to 7.15 (mt: 1H); from 7.25 to 7.40 (mt: 1H); from 7.50 to 7.80 (mt: 3H); 8.00 (mt: 1H); 8.24 (broad d, J = 9 Hz: 1H); 9.05 (d, J = 5 Hz: 1H). (3R, 4R) - Methyl 4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio] ethyl] piperidine-3-carboxylate 120 2 2

En opérant par analogie avec l’exemple 21, mais à partir de (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propylj-l-[2-(2-thiénylthio)éthyl]pipéridine-3-carboxylate deméthyle et de borohydrure de sodium, on obtient 0,95,g de (3R,4R)-4-[3-(R,S)-hydroxy 3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2-thiénylthio)éthyl]pipéridine-3-carboxylate de méthyle sous la forme d’une huile orange.By analogy with Example 21, but starting from (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-methyl-carboxylate and sodium borohydride, there is obtained 0.95 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) ) Propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-carboxylic acid methyl ester as an orange oil.

Spectre infra rouge (CH2C12) : 3600-3150 cm'1 v OH alcool; 2951 cm'1 vCHaliphatiques ; 1732 cm'1 vC=O ;1228 cm'1 v C-O éther ; 103 lcm'1 v C-0 alcool;847 cm'1 γΟΗ quinoline.Infrared spectrum (CH2Cl2): 3600-3150 cm -1 alcohol; 2951 cm -1 Caliphatic; 1732 cm -1 C = 0; 1228 cm -1 C 0 ether; 103 lcm'1 v C-0 alcohol 847 cm'1 γΟΗ quinoline.

Le (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2-thiénylthio)éthyl]pipéridine-3-carboxylate de méthyle peut être préparé par analogie avec l’exemple 4,à partir de (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-carboxylate de méthyle et de 2-(2-chloro-éthylthio)-thiophène.Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-carboxylate can be prepared by analogy with Example 4, from (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate and methyl 2- (2 chloro-ethylthio) thiophene.

Le 2-(2-chloro-éthylthio)-thiophène peut être préparé de la manière suivante :2- (2-chloro-ethylthio) -thiophene can be prepared as follows:

Dans une solution agitée 8,25 cm3 de solution aqueuse de soude à 20 % et de14,6 cm3 de l-bromo-2-chloro-éthane on coule sous agitation à une températurevoisine de 20°C 4,72 cm3 de thiophène-2-thiol. Le mélange est ensuite agité pendant 6heures à une température voisine de 20°C. On ajoute ensuite 40 cm3 d’éther éthylique,la phase organique est lavée par de l’eau, puis séchée sur sulfate de magnésium. Aprèsfiltration sur papier, la solution organique est mélangée sous pression réduite (5 kPa),à une température voisine de 40°C. Le résidu obtenu est purifié par chromatographiesous pression réduite à 50 kPa d’azote sur une colonne de gel de silice (granulométrie20-45 μ ; diamètre 4,5 cm ; poids de silice 250 g), en éluant par un mélange decyclohexane-acétate d’éthyle (95/5 en volumes). On obtient 7,27 g de 2-(2-chloro-éthylthio)-thiophène, sous forme d’une huile mobile de couleur jaune.8.25 cm3 of 20% aqueous sodium hydroxide solution and 14.6 cm3 of 1-bromo-2-chloroethane are stirred in at a temperature of 20 ° C. at a temperature of 20 ° C. 4.72 cm 3 of thiophene-2 thiol. The mixture is then stirred for 6 hours at a temperature in the region of 20 ° C. 40 cm3 of ethyl ether are then added, the organic phase is washed with water and then dried over magnesium sulfate. After filtration on paper, the organic solution is mixed under reduced pressure (5 kPa) at a temperature of 40 ° C. The residue obtained is purified by chromatography under reduced pressure at 50 kPa of nitrogen on a column of silica gel (particle size 20-45 μ, diameter 4.5 cm, weight of silica 250 g), eluting with a cyclohexane-acetate mixture. ethyl (95/5 by volume). 7.27 g of 2- (2-chloroethylthio) -thiophene are obtained in the form of a mobile yellow oil.

Exemple 25Example 25

Dichlorhydrate de l’acide (3R,4R)-4-[3-(R,S)-hydroxy-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-fluorophényl)prop-2-ynyl]pipéridine-3-carboxyIique(3R, 4R) -4- [3- (R, S) -hydroxy- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop-2-dihydrochloride dihydrochloride ynyl] piperidine-3-carboxylic acid

Une solution de 1,3 g de (3R,4R)-4-[3-(R,S)-hydroxy-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(3-fluorophényl)prop-2-ynyl]pipéridine-3-carboxylate de méthyledans 15 cm3 de dioxanne est additionnée de 2,1 cm3 de soude aqueuse 5N, puischauffée à une température voisine de 60cC pendant 16 heures. Aprèsrefroidissement, la solution obtenue est concentrée sous pression réduite (2 kPa), à 120 2 2 205 une température voisine de 45°C. Le résidu obtenu est purifié par chromatographiesous pression d’argon (50 kPa) sur une colonne de gel de silice Amicon(granulométrie 20-45 μ ; diamètre 4 cm ; hauteur 24 cm), en éluant par un. mélange dechloroforme, méthanol et ammoniac (24/12/1 en volumes) et en recueillant desfractions de 30 cm3. Les fractions 41 à 58 sont réunies, puis mélangées sous pressionréduite (2 kPa), à une température voisine de 40°C. On obtient 1,0 g d’une meringuequi est mise en solution dans 8 cm3 d’acétone. Cette solution est ajoutée à 5 cm3d’une solution éther chlorhydrique IN. Après 5 minutes d’agitation, les solide obtenuest filtré puis séché à poids constant sous pression réduite (2 kPa), à une températurevoisine de 40°C. On obtient 820 mg de dichlorhydrate de l’acide (3R,4R)-4-[3-(R,S)-hydroxy-(6-méthoxyquinolin-4-yl)propyl)-l-[3-(3-fluorophényl)prop-2-ynyl]pipéridine-3-carboxylique sous forme d’un solide blanc hygroscopique.A solution of 1.3 g of (3R, 4R) -4- [3- (R, S) -hydroxy- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop) Methyl 2-ynyl] piperidine-3-carboxylate in 15 cm 3 of dioxane is supplemented with 2.1 cm 3 of 5N aqueous sodium hydroxide, and is heated to a temperature in the region of 60 ° C. for 16 hours. Aftercooling, the solution obtained is concentrated under reduced pressure (2 kPa) at a temperature in the region of 45.degree. The residue obtained is purified by chromatography under argon pressure (50 kPa) on an Amicon silica gel column (granulometry 20-45 μ, diameter 4 cm, height 24 cm), eluting with a. mixture of chloroform, methanol and ammonia (24/12/1 by volume) and collecting fractions of 30 cm3. Fractions 41 to 58 are combined and then mixed under reduced pressure (2 kPa) at a temperature in the region of 40 ° C. 1.0 g of a meringue is obtained which is dissolved in 8 cm3 of acetone. This solution is added to 5 cm 3 of an IN hydrochloric ether solution. After stirring for 5 minutes, the solid obtained is filtered and then dried to constant weight under reduced pressure (2 kPa) at a temperature of 40.degree. 820 mg of (3R, 4R) -4- [3- (R, S) -hydroxy- (6-methoxyquinolin-4-yl) propyl) -1- [3- (3-fluorophenyl) dihydrochloride salt are obtained. ) prop-2-ynyl] piperidine-3-carboxylic acid as a hygroscopic white solid.

Spectre de R.M.N. (300 MHz, (CD3)2SO d6 avec ajout de quelques gouttes deCDjCOOD d4, δ en ppm) : de 1,35 à 2,30 et de 2,90 à 3,65 (mts : 12H) ; 3,99 (s :3H) ; de 4,20 à 4,50 (mt : 2H) ; de 5,40 à 5,60 (mt : 1H) ; de 7,25 à 7,70 (mt : 5H) ; de7,70 à 7,80 (mt : 1H) ; 7,99 (mt : 1H) ; 8,20 (d, J = 9 Hz : 1H) ; 9,01 (d large,J = 5 Hz : 1H). (3R,4R)-4-[3-(R,S)-hydroxy-(6-méthoxyquinolin-4-yI)propyl]-l-[3-(3- fluorophényl)prop-2-ynyl]pipéridine-3-carboxylate de méthyle A une solution agitée de 2 g de (3R,4R)-4-[3-oxo-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-fluorophényl)prop-2-ynyl]pipéridine-3-carboxylate de méthyle dans 30 cm3 deméthanol, on ajoute en deux portions, à une température voisine de 20°C et sousatmosphère inerte, 0,193 g de borohydrure de sodium. Le mélange est ensuite agitépendant 3 heures à une température voisine de 20°C. Puis, on ajoute 10 cm3 d’eaudistillée en maintenant la même température. Le mélange, est concentré sous pressionréduite (5 kPa), à une température voisine de 40°C. Le résidu obtenu est repris dans25 cm3 d’eau distillée. Le mélange est extrait par 150 cm3 au total dedichlorométhane. Les phases organiques sont réunies, puis lavées à trois reprises par30 cm3 d’eau puis séchées sur sulfate de magnésium. Après filtration sur papier, puismélange du solvant sous pression réduite (5 kPa), à une température voisine de 40°C,on obtient 1,8 g d’une meringue qui est purifiée par chromatographie sous pressionatmosphérique sur une colonne de gel de silice Amicon (granulométrie 20-45 μ ;diamètre 3 cm ; hauteur 30 cm), en éluant par de l’acétate d’éthyle et en recueillantdes fractions de 50 cm3. Les fractions 17 à 28 sont réunies, puis mélangées sous 206 120 2 2 pression réduite (2 kPa), à une température voisine de 40°C. On obtient ainsi 1,4 g de(3R,4R)-4-[3-(R,S)-hydroxy-(6-méthoxyquinolin-4-yl)propyl]-1 -[3 -(3-fluorophényl)prop-2-ynyl]pipéridine-3-carboxylate de méthyle sous la forme d’unemeringue jaune clair.Spectrum of R.M.N. (300 MHz, (CD3) 2SO d6 with addition of a few drops ofCDjCOOD d4, δ in ppm): from 1.35 to 2.30 and from 2.90 to 3.65 (mts: 12H); 3.99 (s: 3H); from 4.20 to 4.50 (mt: 2H); from 5.40 to 5.60 (mt: 1H); from 7.25 to 7.70 (mt: 5H); from 7.70 to 7.80 (mt: 1H); 7.99 (mt: 1H); 8.20 (d, J = 9 Hz: 1H); 9.01 (broad d, J = 5 Hz: 1H). (3R, 4R) -4- [3- (R, S) -hydroxy- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop-2-ynyl] piperidine-3 methylcarboxylate To a stirred solution of 2 g of (3R, 4R) -4- [3-oxo- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop-2 methyl -piperidine-3-carboxylate in 30 cm3 of methanol, 0.193 g of sodium borohydride are added in two portions, at a temperature in the region of 20.degree. C. and inert subatmosphere. The mixture is then stirred for 3 hours at a temperature of 20 ° C. Then, 10 cm3 of water distilled while maintaining the same temperature. The mixture is concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. The residue obtained is taken up in 25 cm3 of distilled water. The mixture is extracted with 150 cm3 in total of dichloromethane. The organic phases are combined, then washed three times with 30 cm3 of water and then dried over magnesium sulfate. After filtration on paper, and then mixing the solvent under reduced pressure (5 kPa), at a temperature in the region of 40 ° C., 1.8 g of a meringue is obtained which is purified by atmospheric pressure chromatography on an Amicon silica gel column. (20-45 micron size, 3 cm diameter, 30 cm height), eluting with ethyl acetate and collecting 50 cm3 fractions. Fractions 17 to 28 are combined and then mixed under reduced pressure (2 kPa) at a temperature in the region of 40 ° C. 1.4 g of (3R, 4R) -4- [3- (R, S) -hydroxy- (6-methoxyquinolin-4-yl) propyl] -1- [3 - (3-fluorophenyl) propane are thus obtained. Methyl 2-ynyl] piperidine-3-carboxylate as a light yellow meringue.

Le (3R,4R)-4-[3-oxo-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-fluorophényl)prop-2-ynyl] pipéridine-3-carboxylate de méthyle peut être obtenu de la manière suivante : A une solution agitée de 1,97 g de (3R,4R)-4-[3-oxo-(6-méthoxyquinolin-4-yl)propyl]-l-(prop-2-ynyl)pipéridine-3-carboxylate de méthyle dans 40 cm3d’acétonitrile, on ajoute, sous atmosphère inerte, à une température voisine de 20°C,0,404 g de tétrakis(triphényl-phosphine) palladium, 0,118 g de triphénylphosphine et0,191 g d’iodure cuivreux. On ajoute ensuite 0,90 cm3 de 3-fluoroiodobenzène, puis 1,40 cm3 de triéthylamine. Le mélange est agité pendant 15 heures à une températurevoisine de 20°C, puis filtré sur celite. Le gâteau est lavé par 3 fois 10 cm3d’acétonitrile. Les filtrats réunis sont concentrés sous pression réduite (2 kPa), à unetempérature voisine de 40°C. On obtient 4,3 g d’une huile que l’on purifie parchromatographie sous pression atmosphérique, sur une colonne de gel de silice(granulométrie 20-45 μ ; diamètre 3 cm ; hauteur 60 cm), en éluant par l’acétated’éthyle, et en recueillant des fractions de 50 cm3. Les fractions 21 à 42 sont réunies,mélangées sous pression réduite (2 kPa), à une température voisine de 35°C. Onobtient 2 g de (3R,4R)-4-[3-oxo-(6-méthox.yquinolin-4-yl)propyl]-l-[3-(3-fluorophényI)prop-2-ynyl]pipéridine-3-carboxylate de méthyle sous forme d’une huile decouleur jaune.Methyl (3R, 4R) -4- [3-oxo- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop-2-ynyl] piperidine-3-carboxylate may be obtained in the following manner: To a stirred solution of (3R, 4R) -4- [3-oxo- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) 1.97 g ) piperidine-3-carboxylic acid methyl ester in 40 cm3 of acetonitrile, 0.404 g of tetrakis (triphenylphosphine) palladium, 0.118 g of triphenylphosphine and 0.191 g of toluene are added under an inert atmosphere at a temperature in the region of 20.degree. cuprous iodide. Then 0.90 cm3 of 3-fluoroiodobenzene and then 1.40 cm3 of triethylamine are added. The mixture is stirred for 15 hours at a temperature of 20 ° C and then filtered through celite. The cake is washed with 3 times 10 cm3 of acetonitrile. The combined filtrates are concentrated under reduced pressure (2 kPa) at a temperature of 40 ° C. 4.3 g of an oil which is purified by chromatography under atmospheric pressure, on a column of silica gel (particle size 20-45 μ, diameter 3 cm, height 60 cm), eluting with acetated ' ethyl, and collecting 50 cm3 fractions. Fractions 21 to 42 are combined and mixed under reduced pressure (2 kPa) at a temperature in the region of 35 ° C. 2 g of (3R, 4R) -4- [3-oxo- (6-methoxylquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop-2-ynyl] piperidine 3 are obtained. methyl carboxylate as a yellow-colored oil.

Le (3R,4R)-4-[3-oxo-(6-méthoxyquinolin-4-yl)propyl]-l-(prop-2-ynyl)pipéridine-3-carboxylate de méthyle peut être obtenu de la manière suivante : A une suspension agitée de 15 g de dichlorhydrate de (3R,4R)-4-[3-oxo-(6-methoxy-quinolin-4-yl)-propyl]-pipéridine-3-carboxylate de méthyle, dans 150 cm3 dediméthylformamide anhydre, et sous atmosphère inerte, on ajoute, à une températurevoisine de 20°C, 19,6 cm3 de triéthylamine, puis au bout de 45 minutes, 3,95 cm3 debromure de propargyle dilués dans 5 cm3 de diméthylformamide anhydre. Après15 minutes d’agitation à une température voisine de 20°C, le mélange est chauffépendant 4 heures à une température voisine de 45°C. Après refroidissement, lemélange réactionnel est versé dans un mélange de 150 cm3 d’acétate d’éthyle et150 cm3 d’eau distillée. Le mélange est agité quelques minutes, puis la phase 120 2 2 207 organique est décantée. La couche aqueuse est extraite par 2 fois 150 cm3 d’acétated’éthyle. Les phases organiques sont réunies, lavées par 3 fois 200 cm3 d’eau distillée,séchées sur sulfate de sodium. Après filtration, puis mélange du solvant sous pressionréduite (2 kPa), à une température voisine de 40°C, on obtient 13,8 g d’une huile quel’on purifie par chromatographie sous pression d’argon (50 kPa), sur une colonne degel de silice (granulométrie 40-63 μ ; diamètre 5 cm ; hauteur 34 cm), en éluant parun mélange d’acétate d’éthyle et de cyclohexane (9/1 en volumes) jusqu’à la fraction40 puis par de l’acétate d’éthyle pour les suivantes et en recueillant des fractions de50 cm3. Les fractions 23 à 70 sont réunies, puis mélangées sous pression réduite (2kPa), à une température voisine de 45°C. On obtient 8,2 g (3R,4R)-4-[3-oxo-(6-méthoxyquinoIin-4-yl)propyl]- l-(prop-2-ynyl)pipéridine-3-carboxylate de méthyle,sous forme d’huile de couleur orangée.Methyl (3R, 4R) -4- [3-oxo- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-carboxylate can be obtained as follows: To a stirred suspension of 15 g of methyl (3R, 4R) -4- [3-oxo- (6-methoxy-quinolin-4-yl) -propyl] -piperidine-3-carboxylate dihydrochloride, in 150 cm 3 of dimethylformamide anhydrous, and under an inert atmosphere, 19.6 cm3 of triethylamine were added at a temperature of 20 ° C, then 3.95 cm3 of propargyl bromide diluted in 5 cm3 of anhydrous dimethylformamide after 45 minutes. After stirring for 15 minutes at a temperature in the region of 20 ° C., the mixture is heated for 4 hours at a temperature in the region of 45 ° C. After cooling, the reaction mixture is poured into a mixture of 150 cm3 of ethyl acetate and 150 cm3 of distilled water. The mixture is stirred for a few minutes and then the organic phase is decanted. The aqueous layer is extracted with twice 150 cm3 of ethyl acetate. The organic phases are combined, washed with 3 times 200 cm3 of distilled water, dried over sodium sulfate. After filtration, and then mixing the solvent under reduced pressure (2 kPa), at a temperature in the region of 40 ° C., 13.8 g of an oil which is purified by chromatography under argon pressure (50 kPa) are obtained on a thaw column of silica (particle size 40-63 μ, diameter 5 cm, height 34 cm), eluting with a mixture of ethyl acetate and cyclohexane (9/1 by volume) up to fraction 40 and then with ethyl acetate for the following and collecting 50 cm3 fractions. Fractions 23 to 70 are combined and then mixed under reduced pressure (2 kPa) at a temperature in the region of 45 ° C. Methyl 8.2 g (3R, 4R) -4- [3-oxo- (6-methoxyquinyl-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-carboxylate are obtained in the form of of orange-colored oil.

Le dichlorhydrate de (3R,4R)-4-[3-oxo-(6-methoxy-quinolin-4-yl)-propyl]-pipéridine-3-carboxylate de méthyle, peut être obtenu comme décrit à l’exemple 21Methyl (3R, 4R) -4- [3-oxo- (6-methoxy-quinolin-4-yl) -propyl] -piperidine-3-carboxylate dihydrochloride can be obtained as described in Example 21

Exemple 26Example 26

Dichlorhydrate de l’acide (3R,4R)-4-[3-(R,S)-hydroxy-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thién-2-yl)prop-2-ynyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) propyl) dihydrochloride dihydrochloride 2-ynyl] piperidine-3-carboxylic acid

Une solution de 1,3 g de (3R,4R)-4-[3-(R,S)-hydroxy-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thién-2-yl)prop-?-ynyl]pipéridine-3-carboxylate de méthyle dans13 cm3 de dioxanne est additionnée de 2 cm3 de soude aqueuse 5N, puis chauffée àune température voisine de 60°C pendant 3 heures. Après refroidissement, la solutionobtenue est concentrée sous pression réduite (2 kPa), à une température voisine de45°C. Le résidu obtenu est repris dans 75 cm3 d’eau distillée. La phase aqueuse estlavée par 75 cm3 au total de dichlorométhane. La phase aqueuse est concentrée jusqu’àun volume voisin de 10 cm3, refroidie à une température voisine de 5°C puis acidifiéeà un pH voisin de 1 par addition d’acide chlorhydrique 5N. Après 12 heuresd’agitation à une température voisine de 20°C, la phase aqueuse est concentrée souspression réduite (2 kPa), à une température voisine de 45°C. Le résidu obtenu estrepris dans 50 cm’ d’acétone. La solution obtenue est concentrée sous pression réduite(2 kPa), à une température voisine de 45°C. Le résidu obtenu est purifié parchromatographie sous pression d’argon (50 kPa) sur une colonne de gel de silice(granulométrie 20-45 μ ; diamètre 3 cm ; hauteur 30 cm), en éluant par un mélange dechloroforme, méthanol et ammoniac (24/12/1 en volumes) et en recueillant des 120 2 2 208 fractions de 15 cm3. Les fractions 19 à 53 sont réunies, puis mélangées sous pressionréduite (2 kPa), à une température voisine de 40°C. On obtient 0,8 g d’une meringuequi est mise en solution dans 7 cm3 de dichlorométhane. Cette solution est ajoutée à9 cm3 d’une solution d’éther chlorhydrique IN. Après 5 minutes d’agitation à unetempérature voisine de 20°C, le solide obtenu est filtré, lavé par 50 cm3 au totald’oxyde de diéthyle puis séché à poids constant sous pression réduite (2 kPa), à unetempérature voisine de 40°C. On obtient 0,92 g de dichlorhydrate de l’acide (3R,4R)- 4-[3-(R,S)-hydroxy-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thién-2-yl)prop-2-ynyl]pipéridine-3-carboxylique sous la forme de cristaux de couleur blanc cassé.A solution of (3R, 4R) -4- [3- (R, S) -hydroxy- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl), 1.3 g Methyl propylamine) piperidine-3-carboxylate in 13 cm 3 of dioxane is treated with 2 cm 3 of 5N aqueous sodium hydroxide and then heated at a temperature in the region of 60 ° C. for 3 hours. After cooling, the solutionobtained is concentrated under reduced pressure (2 kPa) at a temperature in the region of 45.degree. The residue obtained is taken up in 75 cm3 of distilled water. The aqueous phase is washed with a total of 75 cm 3 of dichloromethane. The aqueous phase is concentrated to a volume of about 10 cm3, cooled to a temperature of 5 ° C and then acidified to a pH of about 1 by addition of 5N hydrochloric acid. After stirring for 12 hours at a temperature in the region of 20 ° C., the aqueous phase is concentrated under reduced pressure (2 kPa) at a temperature in the region of 45 ° C. The residue obtained is taken up in 50 cm 3 of acetone. The solution obtained is concentrated under reduced pressure (2 kPa) at a temperature in the region of 45 ° C. The residue obtained is purified by chromatography under argon pressure (50 kPa) on a column of silica gel (particle size 20-45 μ, diameter 3 cm, height 30 cm), eluting with a mixture of chloroform, methanol and ammonia (24 kPa). / 12/1 in volumes) and collecting 2020 fractions of 15 cm3. Fractions 19 to 53 are combined and then mixed under reduced pressure (2 kPa) at a temperature in the region of 40 ° C. 0.8 g of a meringue is obtained which is dissolved in 7 cm3 of dichloromethane. This solution is added to 9 cm 3 of a 1N hydrochloric ether solution. After stirring for 5 minutes at a temperature in the region of 20 ° C., the solid obtained is filtered off, washed with diethyloxide (50 cc in total) and then dried to constant weight under reduced pressure (2 kPa) at a temperature in the region of 40.degree. . 0.92 g of (3R, 4R) -4- [3- (R, S) -hydroxy- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thienate) dihydrochloride salt are obtained. -2-yl) prop-2-ynyl] piperidine-3-carboxylic acid as off-white crystals.

Spectre de R.M.N. (400 MHz, CD3OD d4, δ en ppm) : de 1,50 à 2,30 (mt : 7H) ;3,06 et 3,11 (2 mts : 1H) ; de 3,15 à 3,95 (mt : 4H) ; 4,03 et 4,04 (2s : 3H) ; de 4,15 à 4,45 (mt : 2H) ; 5,55 et 5,66 (2 mts : 1H) ; 7,04 (mt : 1H) ; 7,37 (mt : 1H) ; 7,51 (d,J = 5 Hz : 1H) ; 7,62 et 7,69 (2s larges : 1H) ; 7,77 (dd, J = 9 et 2 Hz : 1H) ; de 8,10 à8,20 (mt : 2H) ; 8,92 et 8,94 (mt : 1H). (3R,4R)-4-[3-(R,S)-hydroxy-(6-méthoxyquinolin-4-yI)propyl]-l-[3-(thién-2-yI)prop-2-ynyI]pipéridine-3-carboxylate de méthyle A une solution agitée de 1,6 g (3R,4R)-4-[3-oxo-(6-méthoxyquinolin-4-yl)propyl]-l- [3-(thién-2-yl)prop-2-ynyl]pipéridine-3-carboxylate de méthyle dans 15 cm3 de méthanol, on ajoute en une portion, à une température voisine de 20°C et sous atmosphère inerte, 0,15 g de borohydrure de sodium. Le mélange est ensuite agité pendant 2,5 heures à une température voisine de 25°C. Puis, on ajoute goutte à goutte en approximativement 10 minutes, 15 cm3 d’eau distillée en maintenant à une température voisine de 15°C. Le mélange est concentré sous pression réduite (5 kPa), à une température voisine de 40°C. Le résidu obtenu est repris dans 20 cm3 d’eau distillée. Le mélange est extrait par 100 cm3 au total de dichlorométhane. Les phases organiques sont réunies, séchées sur sulfate de sodium puis mélangées sous pression réduite (5 kPa), à une température voisine de 40°C. Le solide obtenu est purifié par chromatographie sous pression d’argon (50 kPa) sur une colonne de gel de silice (granulométrie 20-45 μ ; diamètre 3 cm ; hauteur 35 cm), en éluant par un mélange d’acétate d’éthyle et de cvclohexane (8/2 en volumes) et en recueillant des fractions de 15 cm3. Les fractions 38 à 59 sont réunies, puis mélangées sous pression' réduite (2 kPa), à une température voisine de 40°C. On obtient ainsi 1,3 g (3R,4R)-4-[3- (R,S)-hydroxy-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thién-2-yl)prop-2-ynyl] \ pipéridine-3-carboxylate de sous la forme d’une meringue. 120 2 2 209Spectrum of R.M.N. (400 MHz, CD3OD d4, δ in ppm): from 1.50 to 2.30 (mt: 7H), 3.06 and 3.11 (2 mts: 1H); from 3.15 to 3.95 (mt: 4H); 4.03 and 4.04 (2s: 3H); from 4.15 to 4.45 (mt: 2H); 5.55 and 5.66 (2 mts: 1H); 7.04 (mt: 1H); 7.37 (mt: 1H); 7.51 (d, J = 5 Hz: 1H); 7.62 and 7.69 (broad 2s: 1H); 7.77 (dd, J = 9 and 2 Hz: 1H); from 8.10 to 8.20 (mt: 2H); 8.92 and 8.94 (mt: 1H). (3R, 4R) -4- [3- (R, S) -hydroxy- (6-methoxyquinolin-4-yl) propyl] -l- [3- (thien-2-yl) prop-2-ynyI] -piperidine Methyl 3-carboxylate To a stirred solution of 1.6 g (3R, 4R) -4- [3-oxo- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2- In one part, at a temperature in the region of 20 ° C. under an inert atmosphere, 0.15 g of sodium borohydride are added in one portion at a temperature of 20 ° C. and under an inert atmosphere. The mixture is then stirred for 2.5 hours at a temperature in the region of 25 ° C. Then, 15 cm3 of distilled water are added dropwise in approximately 10 minutes while maintaining a temperature in the region of 15 ° C. The mixture is concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. The residue obtained is taken up in 20 cm3 of distilled water. The mixture is extracted with 100 cm3 in total of dichloromethane. The organic phases are combined, dried over sodium sulphate and then mixed under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. The solid obtained is purified by chromatography under argon pressure (50 kPa) on a column of silica gel (particle size 20-45 μ, diameter 3 cm, height 35 cm), eluting with a mixture of ethyl acetate. and cyclohexane (8/2 by volume) and collecting 15 cm3 fractions. Fractions 38 to 59 are combined and then mixed under reduced pressure (2 kPa) at a temperature in the region of 40 ° C. 1.3 g (3R, 4R) -4- [3- (R, S) -hydroxy- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) are thus obtained. prop-2-ynyl] piperidine-3-carboxylate in the form of a meringue. 120 2 2 209

Le (3R,4R)-4-[3-oxo-(6-méthoxyquinoiin-4-yl)propyl]-l-[3-(thién-2-yl)prop-2-ynyl]pipéridine-3-carboxylate de méthyle peut être obtenu de la manière suivante : A une solution agitée de 1,97 g de (3R,4R)-4-[3-oxo-(6-méthoxyquinolin-4-yl)propyl]-l-(prop-2-ynyl)pipéridine-3-carboxylate de méthyle dans 40 cm3d’acétonitrile, on ajoute, sous atmosphère inerte, à une température voisine de 20°C,0,404 g de tétrakis (triphénylphosphine)palladium, 0,118 g de triphénylphosphine et0,191 g d’iodure cuivreux. On ajoute ensuite 0,84 cm3 de 2-iodothiophène, puis 1,40 cm3 de triéthylamine. Le mélange est agité pendant 48 heures à une températurevoisine de 20°C, puis filtré sur celite. Le gâteau est lavé par de l’acétonitrile. Lesfiltrats réunis sont concentrés sous pression réduite (2 kPa), à une température voisinede 40°C. On obtient 4,2 g d’une huile que l’on purifie par chromatographie souspression d’argon (50 kPa), sur une colonne de gel de silice (granulométrie 20-45 μ ;diamètre 3 cm ; hauteur 30 cm), en éluant par un mélange d’acétate d’éthyle et decyclohexane (8/2 en volumes), et en recueillant des fractions de 15 cm3. Les fractions16 à 32 sont réunies, mélangées sous pression réduite (2 kPa), à une températurevoisine de 35°C. On obtient 1,6 g de (3R,4R)-4-[3-oxo-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thién-2-yl)prop-2-ynyl]pipéridine-3-carboxylate de méthyle sous formed’une huile de couleur orange. (3R,4R)-4-[3-oxo-(6-méthoxyquinolin-4-yl)propyl]-l-(prop-2-ynyl)pipéridine-3- carboxylale de méthyle peut être obtenu comme indiqué à l’exemple 25(3R, 4R) -4- [3-Oxo- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-3-carboxylate Methyl can be obtained as follows: To a stirred solution of (3R, 4R) -4- [3-oxo- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2) (1.97 g) -ynyl) piperidine-3-carboxylate in 40 cm3 of acetonitrile, 0.404 g of tetrakis (triphenylphosphine) palladium, 0.118 g of triphenylphosphine and 0.11 g of toluene were added under an inert atmosphere at a temperature of 20 ° C. cuprous iodide. 0.84 cm3 of 2-iodothiophene and then 1.40 cm3 of triethylamine are then added. The mixture is stirred for 48 hours at a temperature of about 20 ° C. and then filtered through celite. The cake is washed with acetonitrile. The combined filtrates are concentrated under reduced pressure (2 kPa) at a temperature in the region of 40 ° C. 4.2 g of an oil which is purified by chromatography under argon (50 kPa) pressure, on a column of silica gel (particle size 20-45 μ, diameter 3 cm, height 30 cm), eluting with a mixture of ethyl acetate and cyclohexane (8/2 by volume), and collecting 15 cm3 fractions. Fractions 16 to 32 are combined, mixed under reduced pressure (2 kPa), at a temperature of about 35 ° C. 1.6 g of (3R, 4R) -4- [3-oxo- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] are obtained. methyl piperidine-3-carboxylate as an orange oil. Methyl (3R, 4R) -4- [3-oxo- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-carboxylic acid can be obtained as indicated in the example 25

Exemple 27Example 27

Monochlorhydrate de l’acide (3R,4R)-4-[3-(R,S)-fluoro-(6-méthoxyquinoIin-4-yl)propyl]-l-[3-(thién-2-yl)prop-2-ynyI]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro (6-methoxyquinin-4-yl) propyl] -1- [3- (thien-2-yl) propyl) monohydrochloride 2-ynyI] -piperidine-3-carboxylic acid

Une solution de 1,6 g de (3R,4R)-4-[3-(R,S)-fluoro-(6-méthoxyquinolin-4-yl)propyl]- l-[3-(thién-2-yl)prop-2-ynyl]pipéridine-3-carboxylate de méthyle dans 16 cm3 dedioxanne est additionnée de 2,5 cm3 de soude aqueuse 5N, puis chauffée à unetempérature voisine de 60°C pendant 50 heures. Après refroidissement, la solutionobtenue est concentrée sous pression réduite (2 kPa), à une température voisine de45°C. Le résidu obtenu est repris dans 50 cm3 d’acétone puis concentré sous pressionréduite (2 kPa), à une température voisine de 45°C. Le résidu obtenu est purifié parchromatographie sous pression d’argon (50 kPa) sur une colonne de gel de silice(granulométrie 20-45 μ ; diamètre 3,5 cm ; hauteur 34 cm), en éluant par un mélangede chloroforme, méthanol et ammoniac (24/12/1 en volumes) et en recueillant des 210 12 0 2 2 fractions de 15 cm3. Les fractions 16 à 28 sont réunies, puis mélangées sous pressionréduite (2 kPa), à une température voisine de 40°C. Le solide est repris dans del’acétone puis concentré sous pression réduite (2 kPa), à une température voisine de45°C. On obtient 0,72 g d’une meringue qui est mise en solution dans 8 cm3 de 5 dichlorométhane. Cette solution est ajoutée à 8 cm3 d’une solution d’étherchlorhydrique IN. Après 15 minutes d’agitation à une température voisine de 20°C, lesolide obtenu est filtré, puis séché à poids constant sous pression réduite (2 kPa), àune température voisine de 40°C. On obtient 0,74 g de monochlorhydrate de l’acide(3R,4R)-4-[3-(R,S)-fluoro-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thién-2-yl)prop-2- 10 ynyl]pipéridine-3-carboxylique sous la forme de cristaux de couleur blanc casséfondant à 166°C.A solution of (3R, 4R) -4- [3- (R, S) -fluoro- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl), 1.6 g ) 2-propyl-2-ynyl] piperidine-3-carboxylate in 16 cm3 of dioxane is added with 2.5 cm3 of 5N aqueous sodium hydroxide, then heated to a temperature of 60 ° C for 50 hours. After cooling, the solutionobtained is concentrated under reduced pressure (2 kPa) at a temperature in the region of 45.degree. The residue obtained is taken up in 50 cm3 of acetone and then concentrated under reduced pressure (2 kPa) at a temperature in the region of 45 ° C. The residue obtained is purified by chromatography under argon pressure (50 kPa) on a column of silica gel (particle size 20-45 μ, diameter 3.5 cm, height 34 cm), eluting with a mixture of chloroform, methanol and ammonia. (24/12/1 in volumes) and collecting 210 12 0 2 2 fractions of 15 cm3. Fractions 16 to 28 are combined and then mixed under reduced pressure (2 kPa) at a temperature in the region of 40 ° C. The solid is taken up in acetone and then concentrated under reduced pressure (2 kPa), at a temperature of 45 ° C. 0.72 g of a meringue is obtained which is dissolved in 8 cm3 of dichloromethane. This solution is added to 8 cm 3 of a 1N hydrochloric acid solution. After stirring for 15 minutes at a temperature in the region of 20 ° C., the resulting solid is filtered and then dried to constant weight under reduced pressure (2 kPa) at a temperature in the region of 40 ° C. 0.74 g of (3R, 4R) -4- [3- (R, S) -fluoro- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien) monohydrochloride salt are obtained. -2-yl) prop-2-ynyl] piperidine-3-carboxylic acid as off-white crystals at 166 ° C.

Spectre de R.M.N. (400 MHz, (CD3)2SO d6, à une température de 383K, δ enppm) : 1,68 (mt : 2H) ; 1,87 (mt : 1H) ; 1,89 (mt : 1H) ; de 2,05 à 2,25 (mt : 3H) ; de3,05 à 3,45 (mt : 5H) ; 3,98 (s : 3H) ; 4,25 (AB limite : 2H) ; 6,31 (mt, JHF = 16 Hz : 15 1H) ; 7,12 (dd, J = 5 et 3,5 Hz : 1H) ; de 7,35 à 7,45 (mt : 2H) ; de 7,45 à 7,55 (mt : 2H) ; 7,64 (d, J = 5 Hz : 1H) ; 8,05 (d, J = 9 Hz : 1H) ; 8,80 (d, J= 5 Hz : 1H). (3R,4R)-4-[3-(R,S)-fluoro-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thién-2-yl)prop- 2-ynyI]pipéridine-3-carboxylate de méthyle A une solution de 3,4 g de (3R,4R)-4-[3-(R,S)-hydroxy-(6-méthoxyquinolin-4-20 yl)propyl]-l-[3-(thién-2-yl)prop-2-ynyl]pipéridine-3-carboxylate de méthyle sousatmosphère inerte dans 50 cm3 de dichlorométhane on additionne goutte à goutte enapproximativement 15 minutes une solution de 1,14 cm3 de diéthylamino trisulfure desoufre dans 10 cm3 de dichlorométhane. Après 9 heures d’agitation à une températurevoisine de 20°C, le mélange réactionnel est refroidi à une température voisine de 25 10°C et 60 cm3 d’une solution saturée en hydrogénocarbonate de sodium est ajoutée en approximativement 15 minutes. La phase organique est décantée puis lavée avec300 cm3 au total d’eau distillée. La phase organique est séchée sur sulfate de sodium,filtrée puis concentrée sous pression réduite (2 kPa) à une température voisine de40°C. Le résidu obtenu est purifié par chromatographie sous pression d’argon 30 (50 kPa) sur une colonne de gel de silice (granulométrie 20-45 μ ; diamètre 4 cm ; hauteur,31 cm), en éluant par un mélange d’acétate d’éthyle et de cyclohexane (1/1 envolumes) et en recueillant des fractions de 15 cm3. Les fractions 34 à 65 sont réunies,puis mélangées sous pression réduite (2 kPa), à une température voisine de 40°C. Lesolide ëst repris dans de l’acétone puis concentré sous pression réduite (2 kPa), à une 211 120 2 2 température voisine de 45°C. On obtient 1,8 g de 0.74 g de (3R,4R)-4-[3-(R,S)-fluoro-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thién-2-yl)prop-2-ynyl]pipéridine-3-carboxylate de méthyle sous la forme d’une huile jaune.Spectrum of R.M.N. (400 MHz, (CD3) 2SO d6, at a temperature of 383K, δppm): 1.68 (mt: 2H); 1.87 (mt: 1H); 1.89 (mt: 1H); from 2.05 to 2.25 (mt: 3H); from 3.05 to 3.45 (mt: 5H); 3.98 (s: 3H); 4.25 (AB limit: 2H); 6.31 (mt, JHF = 16Hz: 1H); 7.12 (dd, J = 5 and 3.5 Hz: 1H); from 7.35 to 7.45 (mt: 2H); from 7.45 to 7.55 (mt: 2H); 7.64 (d, J = 5 Hz: 1H); 8.05 (d, J = 9 Hz: 1H); 8.80 (d, J = 5 Hz: 1H). (3R, 4R) -4- [3- (R, S) -Fluoro (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-yl] piperidine Methyl 3-carboxylate To a solution of (3R, 4R) -4- [3- (R, S) -hydroxy- (6-methoxyquinolin-4-yl) propyl] -1- (3.4 g) Methyl 3- (thien-2-yl) prop-2-ynyl] piperidine-3-carboxylate subatmosphere inert in 50 cm3 of dichloromethane is added dropwise over approximately 15 minutes a solution of 1.14 cm 3 of diethylamino trisulfide desoufre in 10 cm3 of dichloromethane. After stirring for 9 hours at a temperature of about 20 ° C., the reaction mixture is cooled to a temperature in the region of 10 ° C. and 60 cm 3 of a saturated solution of sodium hydrogencarbonate is added in approximately 15 minutes. The organic phase is decanted and washed with 300 cm3 in total of distilled water. The organic phase is dried over sodium sulfate, filtered and then concentrated under reduced pressure (2 kPa) at a temperature in the region of 40 ° C. The residue obtained is purified by chromatography under argon pressure (50 kPa) on a column of silica gel (particle size 20-45 μ, diameter 4 cm, height 31 cm), eluting with a mixture of acetate of d ethyl and cyclohexane (1/1 volumetric) and collecting 15 cm3 fractions. Fractions 34 to 65 are combined and then mixed under reduced pressure (2 kPa) at a temperature in the region of 40 ° C. The solids are taken up in acetone and then concentrated under reduced pressure (2 kPa) at a temperature in the region of 45.degree. 1.8 g of (3R, 4R) -4- [3- (R, S) -fluoro- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2), 0.74 g are obtained. Methyl-propyl-2-ynyl] piperidine-3-carboxylate as a yellow oil.

Le (3R,4R)-4-[3-(R,S)-hydroxy-(6-méthoxyquinoîin-4-yl)propyl]-1 -[3-(thién-2-yl)prop-2-ynyl]pipéridine-3-carboxylate de méthyle peut être préparé comme décrit àl’exemple 26.(3R, 4R) -4- [3- (R, S) -hydroxy- (6-methoxyquinin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] Piperidine-3-carboxylic acid methyl ester can be prepared as described in Example 26.

Exemple 28Example 28

Dichlorhydrate de l’acide (3R,4R)-4-[3-(R,S)-fIuoro-(6-méthoxyquinoIin-4-yI)propyl]-l-[3-(3~fluorophényl)prop-2-ynyIÎpipéridine~3-carboxylique(3R, 4R) -4- [3- (R, S) -Fluoro- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop-2-dihydrochloride ynyIÎpipéridine ~ 3-carboxylic acid

Une solution de 1,48 g de (3R,4R)-4-[3-(R,S)-fluoro-(6-méthoxyquinolin-4-yl)propyl]-l -[3-(3-fluorophényl)prop-2-ynyl]pipéridine-3-carboxylate de méthyledans 15 cm3 de dioxanne et de 2,4 cm3 de soude aqueuse 5N, est chauffée à unetempérature voisine de 60°C pendant 17 heures. Après refroidissement, la solutionobtenue est concentrée sous pression réduite (2 kPa), à une température voisine de45°C. Le résidu obtenu est repris dans 50 cm3 d’acétone puis concentré sous pressionréduite (2 kPa), à une température voisine de 45°C. Le résidu obtenu est purifié parchromatographie sous pression atmosphérique sur une colonne de gel de silice(granulométrie 20-45 μ ; diamètre 2,8 cm ; volume : 150 cm3), en éluant par unmélange de dichlorométhane, méthanol et ammoniac (.120/20/3 en volumes) et enrecueillant des fractions de 20 cm3. Les fractions contenant le produit attendu sontréunies, puis mélangées sous pression réduite (2 kPa), à une température voisine de40°C. Le solide est repris dans 25 cm3 d’acétone puis on ajoute 5 cm3 d’une solutiond’éther chlorhydrique 1N et 20 cm3 d’oxyde de diéthyle. Après 2 heures d’agitation àune température voisine de 20°C, le solide obtenu est filtré, puis séché à poidsconstant sous pression réduite (2 kPa), à une température voisine de 40°C. On obtient0.6 g de dichlorhydrate de l’acide (3R,4R)-4-[3-(R,S)-fluoro-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-fluorophényl)prop-2-ynyl]pipéridine-3-carboxylique sous la formed’un solide.A solution of 1.48 g of (3R, 4R) -4- [3- (R, S) -fluoro- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop) Methyl 2-ynyl] piperidine-3-carboxylate in 15 cm 3 of dioxane and 2.4 cm 3 of 5N aqueous sodium hydroxide is heated to a temperature of 60 ° C for 17 hours. After cooling, the solutionobtained is concentrated under reduced pressure (2 kPa) at a temperature in the region of 45.degree. The residue obtained is taken up in 50 cm3 of acetone and then concentrated under reduced pressure (2 kPa) at a temperature in the region of 45 ° C. The residue obtained is purified by chromatography under atmospheric pressure on a column of silica gel (particle size 20-45 μ, diameter 2.8 cm, volume: 150 cm 3), eluting with a mixture of dichloromethane, methanol and ammonia (. / 3 in volumes) and collecting fractions of 20 cm3. The fractions containing the expected product are then combined and then mixed under reduced pressure (2 kPa) at a temperature in the region of 40 ° C. The solid is taken up in 25 cm3 of acetone and then 5 cm3 of a solution of 1N hydrochloric ether and 20 cm3 of diethyl ether are added. After stirring for 2 hours at a temperature in the region of 20 ° C., the solid obtained is filtered and then dried at constant weight under reduced pressure (2 kPa) at a temperature in the region of 40 ° C. 0.6 g of (3R, 4R) -4- [3- (R, S) -fluoro- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3- (3 - (3-yl) dihydrochloride salt are obtained. fluorophenyl) prop-2-ynyl] piperidine-3-carboxylic acid as a solid.

Spectre de R.M.N. (400 MHz, (CDj^SO d6, à une température de 373K, δ enppm) : de 1,55 à 1,95 (mt : 3H) ; de 2,00 à 2,30 (mts : 4H) ; de 3,15 à 3,50 (mt : 5H) ;3,99 (s : 3H) ; 4,31 (AB limite : 2H) ; 6,38 (mt, JKF = 47 Hz : 1H) ; de 7,25 à 7,55(mt : 5H) ; 7,55 (dd, J = 9 et 2,5 Hz : 1H) ; 7,60 (d, J = 5 Hz : 1H) ; 8,12 (d, J = 9 Hz :1H) ; 8,84 (d, J = 5 Hz: 1H). 1 20 2 2 212 (3R,4R)-4-[3-(R,S)-fluoro-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-fluorophényI)prop-2-ynyl]pipéridine-3-carboxyïate de méthyle A une solution de 4,2 g de (3R,4R)-4-[3-(R,S)-hydroxy-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-fluorophényl)prop-2-ynyl]pipéridine-3-carboxylate de méthyle sousatmosphère inerte dans 75 cm3 de dichloromettiane refroidie a une températurevoisine de 15°C, on additionne goutte à goutte en approximativement 15 minutes unesolution de 1,4 cm3 de diéthylamino trisulfure de soufre dans 5 cm3 dedichlorométhane. Après 9 heures d’agitation à une température voisine de 25°C, Onajoute 100 cm3 d’une solution saturée en hydrogéno-carbonate de sodium en veillant àce que la température de dépasse pas 25°C. La phase organique est décantée puislavée avec 100 cm3 au total d’eau distillée. La phase organique est séchée sur sulfatede magnésium, filtrée puis concentrée sous pression réduite (2 kPa) à une températurevoisine de 40°C. Le résidu obtenu est purifié par chromatographie sous pressionatmosphérique sur une colonne de gel de silice (granulométrie 20-45 μ ; diamètre4 cm; hauteur 42 cm), en éluant par de l’acétate d’éthyle et en recueillant desfractions de 70 cm3. Les fractions 19 à 35 sont réunies, puis mélangées sous pressionréduite (2 kPa), à une température voisine de 40°C. Le solide est repris dans del’acétone puis concentré sous pression réduite (2 kPa), à une température voisine de45°C. On obtient 3,1 g (3R,4R)-4-[3-(R,S)-fluoro-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-fluorophényl)prop-2-ynyl]pipéridine-3-carboxylate de méthyle sous la formed’une huile jaune.Spectrum of R.M.N. (400 MHz, (CD 4 SO 4 d6, at a temperature of 373K, δ ppm): 1.55 to 1.95 (mt: 3H), 2.00 to 2.30 (mts: 4H); , 15 to 3.50 (mt: 5H), 3.99 (s: 3H), 4.31 (AB limit: 2H), 6.38 (mt, JKF = 47 Hz: 1H), from 7.25 to 7.55 (mt: 5H), 7.55 (dd, J = 9 and 2.5 Hz: 1H), 7.60 (d, J = 5 Hz: 1H), 8.12 (d, J = 9), Hz: 1H); 8.84 (d, J = 5 Hz: 1H). 1 2 2 212 (3R, 4R) -4- [3- (R, S) -fluoro- (6-methoxyquinolin-4-) yl) methyl propyl] -1- [3- (3-fluorophenyl) prop-2-ynyl] piperidine-3-carboxyate To a solution of 4.2 g of (3R, 4R) -4- [3- (R) Methyl (S) -hydroxy- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop-2-ynyl] piperidine-3-carboxylate subatmosphere inert in 75 cm3 of dichloromethane, cooled at room temperature. At a temperature of about 15 ° C., a solution of 1.4 cm 3 of diethylamino sulfur triisulfide in 5 cm 3 of dichloromethane is added dropwise in approximately 15 minutes, after stirring for 9 hours at a temperature in the region of 25 ° C. 100 cm 3 are added. d a saturated solution of sodium hydrogen carbonate ACE ensuring that the temperature not exceed 25 ° C. The organic phase is decanted and washed with 100 cm3 in total of distilled water. The organic phase is dried over magnesium sulphate, filtered and then concentrated under reduced pressure (2 kPa) at a temperature of 40 ° C. The residue obtained is purified by atmospheric pressure chromatography on a column of silica gel (particle size 20-45 μ, diameter 4 cm, height 42 cm), eluting with ethyl acetate and collecting fractions of 70 cm 3. Fractions 19 to 35 are combined and then mixed under reduced pressure (2 kPa) at a temperature in the region of 40 ° C. The solid is taken up in acetone and then concentrated under reduced pressure (2 kPa), at a temperature of 45 ° C. 3.1 g (3R, 4R) -4- [3- (R, S) -fluoro- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop-2 are obtained. methyl -pyridine-3-carboxylate in the form of a yellow oil.

Le (3R,4R)-4-[3-(R,S)-hydroxy-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3-fluorophényl)prop-2-ynyl]pipéridine-3-carboxylate de méthyle peut être préparé commedécrit à l’exemple 25(3R, 4R) -4- [3- (R, S) -hydroxy- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) prop-2-ynyl] piperidine- Methyl 3-carboxylate can be prepared as described in Example 25

Exemple 29 (3R,4R)-3-hydroxyméthyI-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyI]-l-[3-(thièn-2-yl)prop-2-ynyI] pipéridine A un mélange sous agitation de 0,5 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thièn-2-yl)prop-2-ynyl] pipéridine-3-carboxylatede méthyle dans 10 cm3 de toluène, refroidie à -20°C, on ajoute 4,2 cm3 d’une solutionà 20 % d’hydrure de diisobutyl aluminium dans le toluène. L’agitation est maintenue3 heures à cette température puis on ajoute 15 cm3 d’une solution saturée de chlorured’ammonium, maintient l’agitation 15 minutes et laisse remonter la température à une il20 22 213 température proche de 20°C. La phase aqueuse est décantée, séchée sur sulfate demagnésium anhydre, filtrée et concentrée à sec sous pression réduite (2 kPa). Lerésidu obtenu est purifié par chromatographie sur colonne de gel de silice(granulométrie 20-45 μ ; diamètre 2 cm ; hauteur 20 cm), en éluant, sous une pressionde 50 kPa d’azote par du dichlorométhane puis un mélange de dichlorométhane et deméthanol (95/5 en volumes) et en recueillant des fractions de 30 cm3. Les fractions 14à 16 sont réunies, puis mélangées sous pression réduite (5 kPa), à une températurevoisine de 40°C. Le résidu obtenu est repris par 5 cm3 de dichlorométhane et filtré. Lefiltrat est concentré à sec sous pression réduite (2 kPa). On obtient 0,17 g de (3R,4R)- 3-hydroxyméthyl-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yî)propyl]-l-[3-(thièn-2-yl)prop-2-ynyl) pipéridine sous forme d’une gomme.Example 29 (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) ) prop-2-ylyl] piperidine To a stirred mixture of 0.5 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl) ] -ethyl 1- [3- (thien-2-yl) prop-2-ynyl] piperidine-3-carboxylate in 10 cm3 of toluene, cooled to -20 ° C, 4.2 cm3 of a 20% solution are added. % of diisobutyl aluminum hydride in toluene. Stirring is maintained for 3 hours at this temperature, then 15 cm 3 of a saturated solution of ammonium chloride are added, stirring is maintained for 15 minutes and the temperature is allowed to rise to a temperature close to 20 ° C. The aqueous phase is decanted, dried over anhydrous magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa). The residue obtained is purified by chromatography on a column of silica gel (particle size 20-45 μ, diameter 2 cm, height 20 cm), eluting, under a pressure of 50 kPa of nitrogen with dichloromethane and then a mixture of dichloromethane and ethanol ( 95/5 by volume) and collecting fractions of 30 cm3. Fractions 14 to 16 are combined and then mixed under reduced pressure (5 kPa) at a temperature of 40 ° C. The residue obtained is taken up in 5 cm3 of dichloromethane and filtered. Lefiltrat is concentrated to dryness under reduced pressure (2 kPa). 0.17 g of (3R, 4R) -3-hydroxymethyl-4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- ( thien-2-yl) prop-2-ynyl) piperidine in the form of a gum.

Spectre de R.M.N. (400 MHz, (CD3)2SO d6, δ enppm) : de 1,25 à 1,90 (mt : 8H) ; 2,22 (mt : 2H) ; de 2,65 à 2,90 (mt : 2H) ; de 3,35 à 3,60 (mt : 4H) ; 3,91 et 3,93 (2s :3H) ; 4,29 (mf : 1H) ; 5,28 (mt : 1H) ; 5,50 et 5,52 (2d, J = 4,5 Hz : 1H) ; 7,07 (mt :1H) ; 7,28 (dd, J =-- 4 et 1 Hz : 1H) ; de 7,35 à 7,45 (mt : 2H) ; de 7,50 à 7,60 (mt :2H) ; 7,95 (d, J = 9 Hz : 1H) ; 8,71 (d, J = 5 Hz : 1H).Spectrum of R.M.N. (400 MHz, (CD3) 2SO d6, δ enppm): from 1.25 to 1.90 (mt: 8H); 2.22 (mt: 2H); from 2.65 to 2.90 (mt: 2H); from 3.35 to 3.60 (mt: 4H); 3.91 and 3.93 (2s: 3H); 4.29 (mf: 1H); 5.28 (mt: 1H); 5.50 and 5.52 (2d, J = 4.5 Hz: 1H); 7.07 (mt: 1H); 7.28 (dd, J = - 4 and 1 Hz: 1H); from 7.35 to 7.45 (mt: 2H); from 7.50 to 7.60 (mt: 2H); 7.95 (d, J = 9 Hz: 1H); 8.71 (d, J = 5 Hz: 1H).

Le (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propylj-l-[3-(thièn-2-yl)prop-2-ynyl] pipéridine-3-carboxylate de méthyle est obtenu comme décrit àl’exemple 26(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl) ] Piperidine-3-carboxylic acid methyl ester is obtained as described in Example 26

ExempL 30 (3R,4R)-4-[3-(R,S)-Hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-3-hydroxyméthyl 1-(2-(1,3-thiazol-2-ylthio)éthyl]-3-pipéridîneExample 30 (3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -3-hydroxymethyl 1- (2- (1,3-thiazole) 2-ylthio) ethyl] -3-piperidine

En opérant par analogie avec l’exemple 21, mais à partir de (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]-1-(2-(1,3-thiazol-2-ylthio)éthyl]pipéridine-3-carboxylate de méthyle et de borohydrure de sodium, on obtient 0,33 g de (3R,4R)-4-(3-(R,S)-hydroxy-3 -(6-méthoxyquinolin-4-yl)propyl)-3-hydroxyméthyl-1 -[2-( 1,3-thiazol-2-ylthio)éthyl]-3-pipéridine, sous la forme d’une huile.By analogy with Example 21, but starting from (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (2- (1,3) Methyl-thiazol-2-ylthio) ethyl] piperidine-3-carboxylate and sodium borohydride, 0.33 g of (3R, 4R) -4- (3- (R, S) -hydroxy-3 - (6-Methoxyquinolin-4-yl) propyl) -3-hydroxymethyl-1- [2- (1,3-thiazol-2-ylthio) ethyl] -3-piperidine as an oil.

Spectre de R.M.N. ^H (300 MHz, (CD3)2SO d6, δ en ppm) : de 1,10 à 2,20 - de 2,55 à2,90 et de 3,30 à 3,60 (mts : 16H) ; 2,60 (t, J = 6,5 Hz : 2H) ; 3,93 et 3,94 (2s : 3H) ; 4,26 (mf : 1H) ; 5,27 (mt : 1H) ; de 5,50 à 5,60 (mt : 1H) ; de 7,35 à 7,45 (mt : 2H) ;7,56 (mt : 1H) ; 7,63 (d, J = 3 Hz : 1H) ; 7,71 (d, J = 3 Hz : 1H) ; 7,95 (d, J = 9 Hz :1H) ; 8,72 (d, J = 5 Hz : 1H). 120 2 2 214Spectrum of R.M.N. H (300 MHz, (CD3) 2SO d6, δ in ppm): from 1.10 to 2.20 - from 2.55 to 2.90 and from 3.30 to 3.60 (mts: 16H); 2.60 (t, J = 6.5 Hz: 2H); 3.93 and 3.94 (2s: 3H); 4.26 (mf: 1H); 5.27 (mt: 1H); from 5.50 to 5.60 (mt: 1H); 7.35 to 7.45 (mt: 2H), 7.56 (mt: 1H); 7.63 (d, J = 3 Hz: 1H); 7.71 (d, J = 3 Hz: 1H); 7.95 (d, J = 9 Hz: 1H); 8.72 (d, J = 5 Hz: 1H). 120 2 2 214

Le (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(l,3-thia2ol-2-ylthio)éthyl] pipéridine-3-carboxylate de méthyle est préparé par analogie avec l’exemple 4à partir de (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl3pipéridine-3-carboxylate de méthyle et de 2-bromo-l-(l,3-thiazol-2-ylthio)éthane.(3R, 4R) -4- [3-Oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (1,3-thia2ol-2-ylthio) ethyl] piperidine-3 Methyl carboxylate is prepared by analogy with Example 4 from (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylic acid methyl ester and 2-bromo -l- (l, 3-thiazol-2-ylthio) ethane.

Le (3R,4R)- 4-[3-oxo 3-(6-méthoxyquinoiin-4-yl)propyl] pipéridine-3-carboxylate deméthyle est préparé comme décrit dans l’exemple 21.(3R, 4R) -4- [3-Oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylic acid methyl ester is prepared as described in Example 21.

Exemple 32Example 32

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyI]-l-[3-(thién-3-yl)prop-2-ynyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop-2- acid) ynyl] piperidine-3-carboxylic acid

Une solution de 0,73 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thién-3-yl)prop-2-ynyl]pipéridine-3-carboxylate de méthyle, 7,6 cm3 dedioxanne et 1,22 cm3 de soude aqueuse 5N est chauffée à une température voisine de60°C, sous agitation pendant 3 heures 30 minutes. Après refroidissement à unetempérature voisine de 20°C, le mélange réactionnel est concentré sous pressionréduite (5 kPa) à une température voisine de 40°C. Le résidu obtenu est purifié parchromatographie sous pression d’argon (55 kPa) sur une colonne de gel de silice(granulométrie 40-63μ ; diamètre 5 cm ; volume silice 120 cm3) en éluant d’abord par1120 cm3 d’un mélange de dichlorométhane-méthanol-acétonitrile (92/8/7 envolumes). On élue ensuite par 224 cm3 du même mélange (mais de composition92/12/7 en volumes), puis 224 cm3 du même mélange (de composition 92/16/7 envolumes), puis 400 cm3 de mélange dichlorométhane-méthanol (50/50 en volumes) etenfin 400 cm3 de méthanol pur. On recueille une fraction de 112 cm3, puis desfractions de 7 cm3. Les fractions 173 à 468 sont réunies puis évaporées sous pressionréduite (2 kPa) à une température voisine de 35°C. On obtient une meringue que l’onsèche sous pression réduite (30 Pa) à une température voisine de 30°C pendant 4 à 5heures. On obtient 0,33 g d’ acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thién-3-yl)prop-2-ynyl]pipéridine-3-carboxyliquesous forme d’un solide d’aspect meringué, de couleur beige, fondant à 113-115°C.A solution of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3), 0.73 g. Methyl (-yl) prop-2-ynyl] piperidine-3-carboxylate, 7.6 cm3 of dioxane and 1.22 cm3 of 5N aqueous sodium hydroxide is heated to a temperature of 60 ° C, with stirring for 3 hours 30 minutes. After cooling to a temperature in the region of 20 ° C., the reaction mixture is concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. The residue obtained is purified by chromatography under argon pressure (55 kPa) on a column of silica gel (particle size 40-63μ, diameter 5 cm, silica volume 120 cm 3) eluting firstly with 1120 cm 3 of a mixture of dichloromethane -methanol-acetonitrile (92/8/7 volumes). Then eluted with 224 cm3 of the same mixture (but composition 92/12/7 by volume), then 224 cm3 of the same mixture (of composition 92/16/7 volumes), then 400 cm3 of dichloromethane-methanol mixture (50/50). in volumes) and finally 400 cm3 of pure methanol. A fraction of 112 cm 3 is collected, followed by fractions of 7 cm 3. Fractions 173 to 468 are combined and then evaporated under reduced pressure (2 kPa) at a temperature in the region of 35 ° C. A meringue is obtained which is dried under reduced pressure (30 Pa) at a temperature of 30 ° C for 4 to 5 hours. 0.33 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien) 3-yl) prop-2-ynyl] piperidine-3-carboxylic acid in the form of a beige meringue-like solid, mp 113-115 ° C.

Spectre de R.M.N. 'H (300 MHz, (CD3)2SO d6, δ en ppm). On observe un mélange dedeux diastéréoisomères : de 1,40 à 1,95 et de 2,30 à 2,95 (mts : 12H) ; 3,53 et 3,55 (2s : 2H en totalité) ; 3,90 et 3,92 (2s : 3H en totalité) ; 5,24 (mt : 1H) ; de 5,35 à 5,65 (mf étalé : 1H) ;7,14 (d, J = 215 12022 5 Hz : 1H) ; de 7,30 à 7,45 (mt : 2H) ; 7,53 et 7,55 (2d, J = 5 Hz : 1H en totalité) ;7,60 (dd, J = 5 et 3 Hz : 1H) ; 7,74 (mt : 1H) ; 7,94 (d, J = 9,5 Hz : 1H) ; 8,70 (d, J = 5Hz : 1H). (3R,4R)-4-[3-(R,S)-Hydroxy-3-(6-méthoxyquinolin-4-yI)propyl]-l-[3-(thién-3-yl)prop-2-ynyl]pipéridine-3-carboxylate de méthyleSpectrum of R.M.N. H (300 MHz, (CD3) 2SO d6, δ in ppm). A mixture of two diastereoisomers is observed: from 1.40 to 1.95 and from 2.30 to 2.95 (mts: 12H); 3.53 and 3.55 (2s: 2H in total); 3.90 and 3.92 (2s: 3H in total); 5.24 (mt: 1H); 5.35 to 5.65 (mw spread: 1H), 7.14 (d, J = 215 12022 Hz: 1H); from 7.30 to 7.45 (mt: 2H); 7.53 and 7.55 (2d, J = 5 Hz: 1H in all), 7.60 (dd, J = 5 and 3 Hz: 1H); 7.74 (mt: 1H); 7.94 (d, J = 9.5 Hz: 1H); 8.70 (d, J = 5Hz: 1H). (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -l- [3- (thien-3-yl) prop-2-ynyl ] methyl piperidine-3-carboxylate

On opère comme pour la préparation du (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thién-3-yl)prop-2-ynyl)pipéridine-3-carboxylate de méthyle, à partir de 1,2 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-(prop-2-ynyl)pipéridine-3-carboxylate de méthyle dans 20 cm3 d’acétonitrile, 0,067 g detriphénylphosphine, 0,227 g de tétrakis(triphénylphosphine)palladiuni, 0,115 gd’iodure cuivreux et 10 cm3 d’acétonitrile puis 0,84 cm3 de triéthylamine, 0,95 g de3-iodothiophène et 5 cm3 d’acétonitrile. Le mélange réactionnel est filtré puis legâteau est lavé par 30 cm3 d’acétonitrile. Le filtrat est évaporé sous pression réduite (2kPa) à une température voisine de 40°C. Le résidu obtenu est repris par 100 cm3 dedichlorométhane. La solution organique résultante est lavée par 3 fois 50 cm3 d’unesolution saturée de chlorure de sodium, séchée sur sulfate de sodium, filtrée puisconcentrée sous pression réduite dans les mêmes conditions que ci-dessus. Le résiduobtenu est purifié par chromatographie sous une pression d’argon de 55 kPa, sur unecolonne de gel de silice (granulométrie 40-63μ ; diamètre 4 cm ; volume silice220 cm3) en cluant par de l’acétate d’éthyle. On recueille une fraction de 180 cm3,puis des fractions de 10 cm3. Les fractions 73 à 300 sont réunies puis concentrées souspression réduite (2 kPa) à une température voisine de 45°C. On obtient 0,96 g d’unproduit que l’on remet en réaction avec 0,76 g de 3-iodothiophène, 0,092 g d’iodurecuivreux, 0,054 g de triphénylphosphine, 0,67 cm3 de triéthylamine et 0,181 g detétrakis(triphénylphosphine)palladium dans 27 cm3 d’acétonitrile à une températurevoisine de 20°C pendant 16 heures. Le mélange réactionnel est filtré ; le gâteau estlavé par 30 cm3 d’acétonitrile. Le filtrat est concentré sous pression réduite (2 kPa) àune température voisine de 40°C. Le résidu obtenu est solubilisé dans 50 cm3 dedichlorométhane ; la solution est lavée par 3 fois 25 cm3 d’une solution saturée dechlorure de sodium, décantée puis séchée sur sulfate de sodium, filtrée et concentréesous pression réduite (2 kPa) à une température voisine de 35°C. On obtient 1,15 gd’un résidu que l’on purifie par chromatographie sous une pression d’argon de 55kPa, sur une colonne de gel de silice (granulométrie 40-63μ ; diamètre 4 cm ; volumesilice 120 cm3) en éluant par l’acétate d’éthyle. On recueille d’abord une fraction de110 cm3 puis des fractions de 8 cm3. Les fractions 68 à 260 sont réunies, concentrées 216 120 2 2 sous pression réduite (2 kPa) à une température voisine de 45°C. On obtient 0,73 g de(3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thién-3-yl)prop-2-ynyl]pipéridine-3-carboxylate de méthyle, sous forme d’une meringue decouleur jaune.The procedure is as for the preparation of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop-2-ynyl) piperidine. Methyl 3-carboxylate, from 1.2 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- ( methyl prop-2-ynyl) piperidine-3-carboxylate in 20 cm3 of acetonitrile, 0.067 g of triphenylphosphine, 0.227 g of tetrakis (triphenylphosphine) palladium, 0.115 g of cuprous iodide and 10 cm3 of acetonitrile followed by 0.84 cm3 of triethylamine, 0.95 g of 3-iodothiophene and 5 cm3 of acetonitrile. The reaction mixture is filtered and the cake is washed with 30 cm3 of acetonitrile. The filtrate is evaporated under reduced pressure (2 kPa) at a temperature of 40 ° C. The residue obtained is taken up in 100 cm3 of dichloromethane. The resulting organic solution is washed with 3 times 50 cm 3 of a solution saturated with sodium chloride, dried over sodium sulfate, filtered under reduced pressure under the same conditions as above. The residue obtained is purified by chromatography under argon pressure of 55 kPa, on a column of silica gel (particle size 40-63μ, diameter 4 cm, silica220 cm3 volume) by cleavage with ethyl acetate. A fraction of 180 cm3 is collected, followed by fractions of 10 cm3. Fractions 73 to 300 are combined and then concentrated under reduced pressure (2 kPa) at a temperature in the region of 45 ° C. 0.96 g of product is obtained which is reacted with 0.76 g of 3-iodothiophene, 0.092 g of iodurecuiveux, 0.054 g of triphenylphosphine, 0.67 cm3 of triethylamine and 0.181 g of detetrakis (triphenylphosphine). palladium in 27 cm3 of acetonitrile at a temperature of 20 ° C for 16 hours. The reaction mixture is filtered; the cake is washed with 30 cm3 of acetonitrile. The filtrate is concentrated under reduced pressure (2 kPa) at a temperature of 40 ° C. The residue obtained is solubilized in 50 cm3 of dichloromethane; the solution is washed with 3 times 25 cm 3 of a saturated solution of sodium chloride, decanted and then dried over sodium sulfate, filtered and concentrated under reduced pressure (2 kPa) at a temperature of 35 ° C. 1.15 g of a residue are obtained which is purified by chromatography under argon pressure of 55 kPa, on a column of silica gel (particle size 40-63 μ, diameter 4 cm, volumes 120 cm 3) eluting with 'ethyl acetate. First a fraction of 110 cm 3 and then fractions of 8 cm 3 are collected. Fractions 68 to 260 are combined and concentrated under reduced pressure (2 kPa) at a temperature in the region of 45 ° C. 0.73 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) are obtained. methyl yl) prop-2-ynyl] piperidine-3-carboxylate as a yellow-colored meringue.

Spectre infra rouge (CC14) 3600-3200 cm'1 vOH; 2950 cm'1 vCH aliphatiques; 1739cm'1 v C=O ; 1241 cm'1 v C-0 éther 626 cm'1 γ CH thiophène (3R,4R)-4-[3-(R,S)-Hydroxy-3-(6-méthoxyquinolin-4-yl)propyI]-l-(prop-2-ynyl)pipéridine-3-carboxylate de méthyleInfrared spectrum (CCl 4) 3600-3200 cm -1 vOH; 2950 cm -1 aliphatic vCH; 1739cm'1 v C = O; 1241 cm -1 C-O ether 626 cm -1 CH thiophene (3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 Methyl (prop-2-ynyl) piperidine-3-carboxylate

Une suspension de 2,45 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-carboxylate de méthyle, 2,1 g de carbonate de potassium, 0,95 gd’iodure de potassium, 0,6 cm3 de bromure de propargyle dans 50 cm3 d’acétonitrileest agitée pendant 40 heures à une température voisine de 20°C, en atmosphère inerte.Après filtration de la masse réactionnelle, le filtrat est évaporé sous pression réduite(5 kPa) à une température voisine de 40°C. Le résidu obtenu est purifié parchromatographie sur une colonne de gel de silice (granulométrie 20-45μ ; diamètre 2,5 cm ; masse 50 g) en éluant par de l’acétate d’éthyle et en recueillant des fractionsde 60 cm3. Les fractions 6 à 12 sont réunies puis concentrées sous pression réduite(5 kPa) à une température voisine de 40°C. On obtient 1,35 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-(prop-2-ynyl)pipéridine-3-carboxylatede méthyle, sous forme d’une gomme.A suspension of 2.45 g of methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate, 2, 1 g of potassium carbonate, 0.95 g of potassium iodide, 0.6 cm3 of propargyl bromide in 50 cm3 of acetonitrile is stirred for 40 hours at a temperature in the region of 20 ° C. in an inert atmosphere. the reaction mass, the filtrate is evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. The residue obtained is purified by chromatography on a silica gel column (particle size 20-45 μ, diameter 2.5 cm, mass 50 g), eluting with ethyl acetate and collecting 60 cm 3 fractions. Fractions 6 to 12 are combined and then concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 1.35 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine are obtained. -3-carboxylated methyl, in the form of a gum.

Spectre infrarouge (CC14) 3600-3200 cm'1 vOH; 3311 cm'1 v CH acétylénique ; 2950cm'1 vCH aliphatiques; 1740 cm'1 v C=O ; 1242 cm'1 v C-0 étherInfrared spectrum (CCl 4) 3600-3200 cm -1 vOH; 3311 cm -1 acetylenic CH; 2950 cm -1 aliphatic vCH; 1740 cm -1 C = O; 1242 cm'1 v C-0 ether

Le 3-iodothiophène peut être préparé selon N.A PETASIS et coll., SYNLETT., 141,(1988).3-iodothiophene can be prepared according to N.A. PETASIS et al., SYNLETT., 141, (1988).

Exemple 33Example 33

Acide (3R,4R)-4-[3-hydroxy-3-(6-méthoxyquinolin-4-yI)propyl]-l-[2-(2- thiénylthio) éthyl]pipéridine-3-carboxy!ique, diastéréoisomère A et acide(3R,4R)-4-[3-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2- thiényIthio)éthyI]pipéridine-3-carboxylique, diastéréoisomère B. 1,36 g d’acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2-thiénylthio)éthyI]pipéridine-3-carboxylique dissous dans 100 cm3 de dichloro- 120 2 2 217 méthane sont chromatographiés sur une colonne de 35 cm et de 6 cm de diamètreconditionnée avec 700 g de silice (granulométrie 5-15 μ) de DAISO. L’élution esteffectuée à l’aide d’un mélange dichlorométhane-méthanol (92/8 en volumes)contenant 0,05 % de triéthylamine. Le débit est de 90 cm3 par minute et la détectioneffectuée en ultra violet à 280 nm. Cette opération conduit à l’obtention des deuxdiastéréo isomères. Les fractions correspondant au premier sont concentrées à sec souspression réduite (5 kPa) à une température voisine de 40°C, puis le résidu obtenu estséché à l’étuve sous pression réduite (13 Pa) à une température voisine de 40°C. Onobtient 0,28 g d’acide (3R,4R)-4-[3-hydroxy-3-(6-méthoxyquinolin-4-yl)propyI]-l-[2-(2-thiénylthio)éthyl]pipéridine-3-carboxylique, diastéréoisomère A. (aD20=-73,8°+/-l,4, dans le dichlorométhane à 0,5 %), sous forme d’une meringue de couleurjaune. Les fractions correspondant au second diastéréoisomère sont traitées commeprécédemment. On obtient 0,46 g d’acide (3R,4R)-4-[3-hydroxy-3-(6-méthoxy-quinolin-4-yl)propylJ-l-[2-(2-thiénylthio)éthyl]pipéridine-3-carboxylique,diastéréoisomère B. (aD20=+71,2°+/-l,2, dans le dichlorométhane à 0,5 %), sousforme d’une meringue jaune. diastéréoisomère A : Spectre de R.M.N. (300 MHz, (CD3)2SO, δ en ppm) : de 1,35à 1,75 et 1,94 (mts : 7H) ; 2,22 (mt : 1H) ; 2,36 (d large, J = 10,5 Hz : 1H) ; de 2,50 à 2,65 (mt : 1H) ; 2,61 (t, J = 7 Hz : 2H) ; 2,76 (mt : 1H) ; de 2,85 à 3,05 (mt : 1H) ; 2,98 (mt : 2H) ; 3,95 (s : 3H) ; 5,22 (mt : 1H) ; 5,51 (d large, J = 4,5 Hz : 1H) ; 7,07(dd, J - 5 et 4 Hz : 111) ; 7,22 (d large, J - 4 Hz : 1H) ; 7,36 (mt : 1H) ; de 7,35 à 7,45(mt : 2H) ; 7,64 (d large, J - 5 Hz : 1H) ; 7,95 (d, J - 9,5 Hz : 1H) ; 8,72 (d, J - 5 Hz :1H). diastéréoisomère B : Spectre de R.M.N. ^H (300 MHz, (CD3)2SO, δ en ppm) : de 1,20à 1,95 (mts : 7H) ; 2,22 (mt : 1H) ; 2,39 (d large, J - 10,5 Hz : 1H) ; de 2,50 à 2,95(mt : 3H) ; 2,60 (t, J = 7 Hz: 2H) ; 2,97 (mt : 2H) ; 3,92 (s : 3H) ; 5,25 (mt : 1H) ; 5,51 (mf : 1H) ; 7,06 (dd, J = 5 et 3,5 Hz : 1H) ; 7,20 (dd, J = 3,5 et 1,5 Hz : 1H) ; 7,40 (mt : 2H) ; 7,53 (d, J = 5 Hz : 1H) ; 7,63 (dd, J = 5 et 1,5 Hz : 1H) ; 7,93 (d, J =10 Hz : 1H) ; 8,70 (d, J = 5 Hz : 1H).(3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-carboxylic acid, diastereoisomeric A and (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-carboxylic acid, diastereoisomeric B. 1.36 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) acid) ethyl] piperidine-3-carboxylic acid dissolved in 100 cm3 of dichloromethane are chromatographed on a 35 cm column and 6 cm diameter packed with 700 g of silica (5-15 μm granulometry) of DAISO. The elution is carried out using a dichloromethane-methanol mixture (92/8 by volume) containing 0.05% triethylamine. The flow rate is 90 cm3 per minute and the detection effected in ultra violet at 280 nm. This operation leads to obtaining the two diastereoisomers. The fractions corresponding to the first are concentrated to dryness under reduced pressure (5 kPa) at a temperature in the region of 40 ° C., and the residue obtained is dried in an oven under reduced pressure (13 Pa) at a temperature in the region of 40 ° C. 0.28 g of (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3 acid is obtained. -carboxylic acid, diastereoisomer A. (aD20 = -73.8 ° +/- 1.4 in 0.5% dichloromethane), as a yellow-colored meringue. The fractions corresponding to the second diastereoisomer are treated as before. 0.46 g of (3R, 4R) -4- [3-hydroxy-3- (6-methoxy-quinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine acid are obtained. -3-carboxylic acid, diastereoisomer B. (aD20 = + 71.2 ° +/- 1, 2, in 0.5% dichloromethane), in the form of a yellow meringue. diastereoisomer A: Spectrum of R.M.N. (300 MHz, (CD3) 2 SO, δ in ppm): from 1.35 to 1.75 and 1.94 (mts: 7H); 2.22 (mt: 1H); 2.36 (broad d, J = 10.5 Hz: 1H); from 2.50 to 2.65 (mt: 1H); 2.61 (t, J = 7 Hz: 2H); 2.76 (mt: 1H); from 2.85 to 3.05 (mt: 1H); 2.98 (mt: 2H); 3.95 (s: 3H); 5.22 (mt: 1H); 5.51 (broad d, J = 4.5 Hz: 1H); 7.07 (dd, J - 5 and 4 Hz: 111); 7.22 (broad d, J - 4 Hz: 1H); 7.36 (mt: 1H); from 7.35 to 7.45 (mt: 2H); 7.64 (bd, 5 Hz: 1H); 7.95 (d, J - 9.5 Hz: 1H); 8.72 (d, J - 5 Hz: 1H). diastereoisomer B: Spectrum of R.M.N. H (300 MHz, (CD3) 2 SO, δ in ppm): from 1.20 to 1.95 (mts: 7H); 2.22 (mt: 1H); 2.39 (broad d, J - 10.5 Hz: 1H); from 2.50 to 2.95 (mt: 3H); 2.60 (t, J = 7 Hz: 2H); 2.97 (mt: 2H); 3.92 (s: 3H); 5.25 (mt: 1H); 5.51 (mf: 1H); 7.06 (dd, J = 5 and 3.5 Hz: 1H); 7.20 (dd, J = 3.5 and 1.5 Hz: 1H); 7.40 (mt: 2H); 7.53 (d, J = 5 Hz: 1H); 7.63 (dd, J = 5 and 1.5 Hz: 1H); 7.93 (d, J = 10 Hz: 1H); 8.70 (d, J = 5 Hz: 1H).

Exemple 34Example 34

Dichlorhydrate de l’acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoIin-4-yl)propylJ-l-(2-(tertiobutyithio)éthyl]pipéridine-3-carboxyLique 218 A une solution de 0,26 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(tertiobutylthio)éthyl]pipéridine-3-carboxylate de méthyle dans 5 cm3 deméthanol, on ajoute sous agitation et sous atmosphère inerte, 1 cm3 de soude aqueuse5 N. Après chauffage de la solution à une température voisine de 60°C, puis 5 refroidissement à température ambiante, la masse réactionnelle est évaporée souspression réduite (2,8 kPa) à une température voisine de 60°C. Le résidu obtenu estrepris par 5 cm3 d’eau distillée, puis on ajoute 5 cm3 d’acide chlorhydrique concentré(d=l, 18). Le mélange est évaporé sous pression réduite (2,8 kPa) à une températurevoisine de 60°C. Le résidu obtenu est repris dans 4 cm3 d’un mélange de 10 dichlorométhane-méthanol (90/10 en volumes). Le précipité blanc obtenu est filtré,lavé par 2 fois 2 cm3 de ce même mélange. Le filtrat est concentré sous pressionréduite (2,8 kPa) à une température voisine de 40°C. Le produit obtenu est séché souspression réduite (16 Pa) à une température voisine de 60°C. On obtient 0,29 g dedichlorhydrate de l’acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl) 15 propyl]-l-[2-(tertiobutylthio)éthyl]pipéridine-3-carboxylique, sous forme d’un solidede couleur beige fondant en se ramollissant au voisinage de 169°C.(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinin-4-yl) propyl] -1- (2- (tert-butylthio) ethyl] piperidine-3-dihydrochloride dihydrochloride -carboxylic acid 218 To a solution of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (0.26 g)) Methyl (tert-butylthio) ethyl] piperidine-3-carboxylate in 5 cm3 of methanol is added with stirring under an inert atmosphere, 1 cm3 of aqueous sodium hydroxide 5 N. After heating the solution to a temperature of 60 ° C, then cooling at room temperature, the reaction mass is evaporated under reduced pressure (2.8 kPa) at a temperature in the region of 60 ° C. The residue obtained is taken with 5 cm 3 of distilled water and then 5 cm 3 of concentrated hydrochloric acid (d = 1, 18) The mixture is evaporated under reduced pressure (2.8 kPa) at a temperature of 60 ° C. The residue obtained is taken up in 4 cm 3 of a mixture of dichloromethane-methanol (90/10 by volume). The white precipitate obtained is filtered, washed twice with 2 cm3 of this same mixture. The filtrate is concentrated under reduced pressure (2.8 kPa) at a temperature in the region of 40 ° C. The product obtained is dried under reduced pressure (16 Pa) at a temperature in the region of 60 ° C. 0.29 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3R, 4R) dihydrochloride is obtained. (tert-butylthio) ethyl] piperidine-3-carboxylic acid, in the form of a beige colored solid melting at about 169 ° C.

Spectre de R.M.N. (400 MHz, (CD3)2SO d6 à une température de 383K, δ enppm). On observe un mélange de deux diastéréoisomères : 1,34 et 1,36 (2s : 9H en totalité) ; de 1,40 à 2,35 et de 2,90 à 3,70 (mts : 12H) ; 3,00 (t 20 large, J = 8 Hz : 2H) ; 3,26 (t, J = 8 Hz : 2H) ; 4,01 (s : 3H) ; 5,40 (mt : 1H) ; de 7,55 à7,70 (mt : 2H) ; 7,82 (mt : 1H) ; 8,22 (d, J = 9 Hz : 1H) ; 8,88 (d, J = 5 Hz : 1H) ; de10,90 à 11,45 (mf étalé : 1H). (3R,4R)-4-[3-(R,S)-Hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(tertiobutylthio)éthyl]pipéridine-3-carboxyIate de méthyle 2 5 On chauffe pendant 16 heures à une température voisine du reflux, sous agitation etsous atmosphère inerte, 0,717 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-carboxylate de méthyle dans 15 cm3d’acétonitrile et 15 cm3 de méthanol avec 0,43 g de 2-chloroéthyltertiobutyl sulfure enprésence de 0,33 g de carbonate de potassium et 0,4 g d’iodure de potassium. Après 30 refroidissement du mélange réactionnel à une température voisine de 20°C,l’insoluble est filtré. Le filtrat est évaporé sous pression réduite (5 kPa) à unetempérature voisine de 40cC. Le résidu obtenu est purifié par chromatographie sousune pression d’azote de 100 kPa sur une^coionne de gel de silice (granulométrie 40-63 219 120 22 μ ; diamètre 3,5 cm ; hauteur 35 cm) en éluant par un mélange de dichlorométhane-méthanol (97/3 en volumes) et en recueillant des fractions de 35 cm3. Les fractions 54à 70 sont réunies puis évaporées sous pression réduite (5 kPa) à une températurevoisine de 40°C. On obtient 0,265 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(tertiobutylthio)éthyl]pipéridine-3-carboxylate deméthyle, sous forme d’une laque de couleur brune.Spectrum of R.M.N. (400 MHz, (CD3) 2SO d6 at a temperature of 383K, δ enppm). There is a mixture of two diastereoisomers: 1.34 and 1.36 (2s: 9H in all); from 1.40 to 2.35 and from 2.90 to 3.70 (mts: 12H); 3.00 (broad t, J = 8 Hz: 2H); 3.26 (t, J = 8 Hz: 2H); 4.01 (s: 3H); 5.40 (mt: 1H); 7.55 to 7.70 (mt: 2H); 7.82 (mt: 1H); 8.22 (d, J = 9 Hz: 1H); 8.88 (d, J = 5 Hz: 1H); from 10.90 to 11.45 (mf spread: 1H). Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (tert-butylthio) ethyl] piperidine-3-carboxyIate 16 g (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4) was heated for 16 hours at a temperature close to reflux with stirring and under an inert atmosphere. methyl-propyl] piperidine-3-carboxylate in 15 cm3 of acetonitrile and 15 cm3 of methanol with 0.43 g of 2-chloroethyltertiobutyl sulfide in the presence of 0.33 g of potassium carbonate and 0.4 g of iodide of potassium. After cooling the reaction mixture to a temperature of 20 ° C, the insoluble material is filtered. The filtrate is evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. The residue obtained is purified by chromatography under a nitrogen pressure of 100 kPa on a silica gel coionne (particle size 40-63 219 120 22 μ, diameter 3.5 cm, height 35 cm) eluting with a mixture of dichloromethane methanol (97/3 by volume) and collecting 35 cm3 fractions. Fractions 54 to 70 are combined and then evaporated under reduced pressure (5 kPa) at a temperature of 40 ° C. 0.265 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (tert-butylthio) ethyl] piperidine are obtained. 3-carboxylate demethyl, in the form of a brown lacquer.

Spectre infra rouge (CC1<) 3550-3100 cm'1 v OH alcool; 2959 cm'1 v CHaliphatiques ; 1736 cm'1 vC=O ;1242 ;1228 cm'1 v C-0 éther ;1034cm'1 v C-O alcool ;853 cm'1 yCH quinolineInfrared spectrum (CCl <) 3550-3100 cm -1 alcohol; 2959 cm -1 Caliphatic; 1736 cm -1 vC = 0; 1242; 1228 cm -1 v C-0 ether; 1034 cm -1 v C-O alcohol; 853 cm -1 yCH quinoline;

Le 2-chloroéthyltertiobutyl sulfure peut être préparé par application de la méthodedécrite dans le brevet EP 136878.2-chloroethyltertiobutyl sulfide can be prepared by application of the method described in EP 136878.

Exemple 35Example 35

Dichlorhydrate de l’acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yI)propyl]-l-[2-(cyclopentylthio)éthyl]pipéridine-3-carboxylique A une solution de 0,48 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(cyclopentylthio)éthyl]pipéridine-3-carboxylate de méthyle dans 10 cm3de méthanol on ajoute sous agitation et sous atmosphère inerte 2 cm3 de soudeaqueuse 5 N. Après 16 heures de chauffage du mélange à une température voisine de60°C, Ja misse réactionnelA est évaporée, sous pression réduite (2,9 kPa) à uneicm fiahue voisine de 60vC, le résidu obtenu, est repris par 4,3 cm3 d’eau distilléeadditionnés de 4,3 cm3 d’acide chlorhydrique à 28%. L’insoluble persistant est filtré,puis le filtrat est évaporé dans les mêmes conditions que ci-dessus. Le résidu obtenuest agité dans un mélange de dichlorométhane-méthanol (90/10 en volumes). Leprécipité résultant est filtré, lavé par 3 fois 2,5 cm3 du même mélange. Le filtrat estévaporé sous pression réduite (5 kPa) à une température voisine de 40°C. On obtient0,48 g de dichlorhydrate de l’acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4 -yl)propyl]-1 -[2-(cyclopenty lthio)éthyl]pipéridine-3-carboxylique,sous forme d’une meringue de couleur verte fondant en se ramollissant à unetempérature voisine de 156°C.(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (2- (cyclopentylthio) ethyl] piperidine acid dihydrochloride 3-carboxylic acid solution of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- Methyl (cyclopentylthio) ethyl] piperidine-3-carboxylate in 10 cm3 of methanol is added with stirring and under an inert atmosphere 2 cm3 of 5 N welder. After 16 hours of heating the mixture to a temperature of 60 ° C, the reaction isA The residue obtained is evaporated under reduced pressure (2.9 kPa) at a temperature of about 60.degree. C. and the residue obtained is taken up with 4.3 cm.sup.3 of distilled water and added with 4.3 cm.sup.3 of 28% hydrochloric acid. The insoluble persistent is filtered and the filtrate is evaporated under the same conditions as above. The residue obtained is stirred in a mixture of dichloromethane-methanol (90/10 by volume). The resulting precipitate is filtered, washed with 3 times 2.5 cm3 of the same mixture. The filtrate is evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 0.48 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (4H) dihydrochloride salt are obtained. cyclopentylthio) ethyl] piperidine-3-carboxylic acid, in the form of a green meringue melt softening at a temperature of about 156 ° C.

Spectre de R.M.N- (400 MHz, (CD3)2SO d6 à une température de 373K, δ enppm). On observe un mélange de deux diastéréoisomères : 120 2 2 220NMR spectrum (400 MHz, (CD3) 2SO d6 at a temperature of 373K, δ enppm). A mixture of two diastereoisomers is observed: 120 2 220

I de 1,45 à 2,30 et de 2,90 à 3,60 (mis : 20H) ; 2,98 (t large, J = 7,5 Hz : 2H) ; 3,22(mt : 1H) ; 3,30 (t, J = 7,5 Hz : 2H) ; 4,00 (s : 3H) ; 5,37 (mt : 1H) ; de 7,50 à 7,65(mt : 2H) ; 7,77 (mt : 1H) ; 8,17 (d, J = 9 Hz : 1H) ; 8,85 (d, J = 5 Hz : 1H). (3R,4R)-4-[3-(R,S)-Hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(cycIopentylthio)éthyl]pipéridine-3-carboxyIate de méthyleI of 1.45 to 2.30 and 2.90 to 3.60 (mis: 20H); 2.98 (broad t, J = 7.5 Hz: 2H); 3.22 (mt: 1H); 3.30 (t, J = 7.5 Hz: 2H); 4.00 (s: 3H); 5.37 (mt: 1H); from 7.50 to 7.65 (mt: 2H); 7.77 (mt: 1H); 8.17 (d, J = 9 Hz: 1H); 8.85 (d, J = 5 Hz: 1H). Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-3-carboxylate

On chauffe pendant 3 h 'Z à une température voisine du reflux, sous agitation et sousatmosphère inerte, 0,717 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-carboxylate de méthyle dans 15 cm3 d’acétonitrile et 15 cm3 deméthanol avec 0,439 g de 2-chloroéthylcyclopentyl sulfure à 90 % en présence de0,332 g de carbonate de potassium et 0,4 g d’iodure de potassium. Aprèsrefroidissement du mélange réactionnel à une température voisine de 20°C,l’insoluble est filtré puis lavé par de racétonitrile. Le filtrat est évaporé sous pressionréduite (5 kPa) à une température voisine de 40°C. Le résidu obtenu est purifié parchromatographie sous une pression d’azote de 100 kPa sur une colonne de gel desilice (granulométrie 40-63μ ; diamètre 3,5 cm ; hauteur 45 cm), en éluant par unmélange de dichlorométhane-méthanol (95/5 en volumes) et en recueillant desfractions de 35 cm3. Les fractions 25 à 45 sont réunies puis évaporées sous pressionréduite (5 kPa) à une température voisine de 40°C. On obtient 0,48 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(cyclopentylthio)éthyl]pipéridine-3-carboxylate de méthyle, sous forme d’une laque de couleur vert-foncé.For 3 hours at a temperature in the vicinity of reflux, with stirring and inert underatmosphere, 0.717 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4 methyl-propyl] piperidine-3-carboxylate in 15 cm3 of acetonitrile and 15 cm3 of methanol with 0.439 g of 90% 2-chloroethylcyclopentyl sulfide in the presence of 0.332 g of potassium carbonate and 0.4 g of potassium iodide. Aftercooling of the reaction mixture at a temperature in the region of 20 ° C., the insoluble material is filtered and then washed with racetonitrile. The filtrate is evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. The residue obtained is purified by chromatography under a nitrogen pressure of 100 kPa on a desilice gel column (particle size 40-63μ, diameter 3.5 cm, height 45 cm), eluting with a mixture of dichloromethane-methanol (95/5 in volumes) and collecting 35 cm3 fractions. Fractions 25 to 45 are combined and then evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 0.48 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] are obtained. Piperidine-3-carboxylic acid methyl ester, in the form of a dark green lacquer.

Spectre infra rouge (CC14) 3550-3100 cm'1 v OH alcool; 2951 cm'1 v CHaliphatiques ; 1736 cm'1 vC=O ; 1242 ; 1228 cm'1 v C-0 éther ;1034cm'* v C-0 alcool ;853 cm'1 yCH quinolineInfrared spectrum (CClO) 3550-3100 cm -1 alcohol; 2951 cm -1 Caliphatic; 1736 cm -1 vC = O; 1242; 1228 cm-1 v C-0 ether, 1034 cm -1 C-0 alcohol, 853 cm -1 yCH quinoline

Le 2-chloroéthylcyclopentyl sulfure peut être préparé par application de la méthodedécrite dans la demande de brevet FR 2 395 260.The 2-chloroethylcyclopentyl sulfide can be prepared by application of the method described in the patent application FR 2,395,260.

Exemple 36Example 36

Dichlorhydrate de l’acide (3R,4R)-l-[2-(3-fluorophényIthio)éthyl]-4-[3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-acétique(3R, 4R) -1- [2- (3-Fluorophenylthio) ethyl] -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetic acid dihydrochloride

Un mélange de 0,48 g de (3R,4R)-l-[2-(3-fluorophénylthio)éthyl]-4-[3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-acétate de méthyle dans 10 cm3 dedioxanne additionnés de 0,78 cm3 de soude aqueuse 5N est agité pendant 20 heures à 120 22 221 une température voisine de 60°C. Après refroidissement à une température voisine de20°C, la masse réactionnelle est évaporée sous pression réduite (5 kPa) à unetempérature voisine de 40°C, puis diluée par 10 cm3 d’eau. Le pH est amené à 4 paraddition d’une quantité suffisante d’une solution aqueuse d’acide citrique. Le mélangeest évaporé sous pression réduite (5 kPa) à une température voisine de 40°C, puis lerésidu obtenu est repris par 70 cm3 d’eau et 20 cm3 d’éthanol. Le mélange est ramenéà pH 9, puis évaporé sous pression réduite (5 kPa) à une température voisine de 50°C.Après reprise du résidu obtenu par 50 cm3 d’un mélange de chloroforme-méthanol-ammoniaque à 28 % (12/3/0,5 en volumes), les sels minéraux sont filtrés. Le filtrat estévaporé sous pression réduite (5 kPa) à une température voisine de 40°C. On obtient 1,2 g d’un produit que l’on purifie par chromatographie sous pression atmosphériquesur une colonne de gel de silice (granulométrie 20-45 μ ; diamètre 2 cm ; hauteur25 cm) en éluant par un mélange de chloroforme-méthanol-ammoniaque à 28 %(12/3/0,5 en volumes), et en recueillant d’abord une fraction de 100 cm3, puis desfractions d’environ 15 cm3. Les fractions 8 à 18 sont réunies puis concentrées souspression réduite (5 kPa) à une température voisine de 40°C. On obtient 0,31 g d’unproduit sous forme d’une meringue de couleur jaune-pâle que l’on agite avec 13 cm3d’acide chlorhydrique aqueux 0,lN pendant 2 heures à une température voisine de20°C. Après addition de 5 cm3 de dioxanne et agitation 2 heures supplémentaires àune température voisine de 20°C, on évapore le dioxanne sous pression réduite (5kPa) à une température voisine de <0°C. La solution obtenue est congelée puislyophilisée. On obtient 0,35 g de dichlorbydraie de l’acide (3R.4K.)-l-[2-(3-'kiorophénylihio) éihyl}4-[3-(ô-méÎhoxyquino]in-4-yi)propyi]pÎpéridine-3~acétique,sous forme de lyophilisai de couleur blanche.A mixture of methyl (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate (0.48 g) in 10 cm3 of dedioxane supplemented with 0.78 cm3 of 5N aqueous sodium hydroxide is stirred for 20 hours at a temperature in the region of 60 ° C. After cooling to a temperature in the region of 20 ° C., the reaction mass is evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. and then diluted with 10 cm 3 of water. The pH is brought to 4 paraddition of a sufficient amount of an aqueous solution of citric acid. The mixture is evaporated under reduced pressure (5 kPa) at a temperature of 40 ° C, then the residue obtained is taken up in 70 cm3 of water and 20 cm3 of ethanol. The mixture is brought to pH 9 and then evaporated under reduced pressure (5 kPa) at a temperature of 50 ° C.After recovery of the residue obtained with 50 cm3 of a mixture of chloroform-methanol-ammonia 28% (12/3 / 0.5 in volumes), the mineral salts are filtered. The filtrate is evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 1.2 g of a product which is purified by chromatography under atmospheric pressure is obtained on a column of silica gel (particle size 20-45 μ, diameter 2 cm, height 25 cm), eluting with a mixture of chloroform-methanol- ammonia at 28% (12/3 / 0.5 by volume), and first collecting a fraction of 100 cm3, then fractions of about 15 cm3. Fractions 8 to 18 are combined and then concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 0.31 g of product is obtained in the form of a pale yellow meringue which is stirred with 13 cm3 of 0.1 N aqueous hydrochloric acid for 2 hours at a temperature in the region of 20 ° C. After addition of 5 cm3 of dioxane and stirring for a further 2 hours at a temperature in the region of 20 ° C., the dioxane is evaporated under reduced pressure (5 kPa) at a temperature in the region of <0 ° C. The solution obtained is frozen and lyophilized. 0.35 g of (3R.4K) -L- [2- (3-kiorophenylthio) hexyl) -4- [3- (6-methoxyquino] -4-yl) propyl] dichlorobutyrate is obtained. 3-β-Piperidine, in the form of white lyophilizate.

Spectre de R.M.K. (400 MHz, (CD3)2SO d6 à une température de 383K, δ enppm) : de 1,45 à 1,95 (mt : 8H) ; 2,33 (dd, J = 16 et 5,5 Hz : 1H) ; de 2,45 à 2,60 (mt :1H) ; de 2,90 à 3,55 (mt : 10H) ; 4,00 (s : 3H) ; 7,06 (t large, J = 8 Hz : 1H) ; 7,28 (d,J = 8 Hz : 2H) ; 7,41 (mt : 1H) ; 7,46 (d, J = 5 Hz : 1H) ; 7,48 (d, J = 2,5 Hz : 1H) ; 7,51 (dd, J = 9,5 et 2,5 Hz : 1H) ; 8,07 (d, J = 9,5 Hz : 1 H) ; 8,72 (d, J = 5 Hz : 1H). (3R,4R)-l-[2-(3-Fluorophénylthio)éthyl]-4-[3-(6-méthoxyquinofin-4- yl)propyl]pipéridine-3-acétate de méthyleSpectrum of R.M.K. (400 MHz, (CD3) 2SO d6 at a temperature of 383K, δppm): from 1.45 to 1.95 (mt: 8H); 2.33 (dd, J = 16 and 5.5 Hz: 1H); from 2.45 to 2.60 (mt: 1H); 2.90 to 3.55 (mt: 10H); 4.00 (s: 3H); 7.06 (broad t, J = 8 Hz: 1H); 7.28 (d, J = 8 Hz: 2H); 7.41 (mt: 1H); 7.46 (d, J = 5 Hz: 1H); 7.48 (d, J = 2.5 Hz: 1H); 7.51 (dd, J = 9.5 and 2.5 Hz: 1H); 8.07 (d, J = 9.5 Hz: 1H); 8.72 (d, J = 5 Hz: 1H). Methyl (3R, 4R) -1- [2- (3-Fluorophenylthio) ethyl] -4- [3- (6-methoxyquinofin-4-yl) propyl] piperidine-3-acetate

Un mélange de 0;76 g de (3R,4R)]-4-[3-(6-méthoxyquinolin-4-yl)propyI]pipéridine-3-acétate de méthyle et 0,42 g de 2-(3-fluorophénylthio)éthyl-l-chlorure dans 15 cm3d’acétonitrile additionnés de 1,4 g de carbonate de potassium et 0,15 g d’iodure de 222 120 2 2 potassium est chauffé sous agitation et sous atmosphère inerte à une températurevoisine de 70°C pendant 20 heures. Après addition de 0,15 g d’iodure de potassium et5 heures supplémentaires de chauffage, le mélange réactionnel est refroidi à unetempérature voisine de 20°C, dilué par 15 cm3 d’eau puis extrait par 2 fois 20 cm3d’acétate d’éthyle. Les extraits réunis sont lavés par 30 cm3 d’acide chlorhydriqueaqueux N. La solution acide est séparée puis rendue alcaline (pH 8-9) par la quantitésuffisante d’une solution saturée aqueuse d’hydrogénocarbonate de sodium. Lemélange est extrait par 2 fois 30 cm3 d’acétate d’éthyle. Les extraits réunis sont séchéssur sulfate de magnésium, filtrés puis évaporés sous pression réduite (5 kPa) à unetempérature voisine de 40°C. On obtient 0,71 g d’une huile que l’on purifie parchromatographie sous pression atmosphérique sur une colonne de gel de silice(granulométrie 20-45μ ; diamètre 2,5 cm ; volume silice 120 cm3) en éluant par unmélange de dichlorométhane-méthanol (99/1 en volumes). On recueille d’abord unefraction de 500 cm3 puis on recueille des fractions de 15 cm3 environ. Les fractions 10à 20 sont réunies puis évaporées sous pression réduite (5 kPa) à une températurevoisine de 40°C. On obtient 0,48 g de (3R,4R)-l-[2-(3-fluorophénylthio)éthyl]-4-[3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-acétate de méthyle, sous forme d’unehuile de couleur jaune.A mixture of 0. 76 g of (3R, 4R)] - methyl 4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate and 0.42 g of 2- (3-fluorophenylthio) ) ethyl-1-chloride in 15 cm3 of acetonitrile supplemented with 1.4 g of potassium carbonate and 0.15 g of potassium iodide is heated with stirring and under an inert atmosphere at a temperature of 70 ° C for 20 hours. After addition of 0.15 g of potassium iodide and 5 additional hours of heating, the reaction mixture is cooled to a temperature of 20 ° C, diluted with 15 cm3 of water and then extracted with 2 times 20 cm3 of ethyl acetate. . The combined extracts are washed with 30 cm3 of N hydrochloric acid. The acid solution is separated and then made alkaline (pH 8-9) by the sufficient amount of a saturated aqueous solution of sodium hydrogencarbonate. Lemix is extracted with 2 times 30 cm3 of ethyl acetate. The combined extracts are dried over magnesium sulfate, filtered and then evaporated under reduced pressure (5 kPa) at a temperature of 40 ° C. 0.71 g of an oil is obtained, which is purified by chromatography under atmospheric pressure on a column of silica gel (particle size 20-45 μ, diameter 2.5 cm, silica volume 120 cm 3), eluting with a mixture of dichloromethane. methanol (99/1 by volume). First a 500 cc fraction is collected and then fractions of about 15 cm3 are collected. Fractions 10 to 20 are combined and then evaporated under reduced pressure (5 kPa) at a temperature of 40 ° C. 0.48 g of (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-methyl acetate are obtained, in the form of a yellow oil.

Spectre infra rouge (CH2C12) 2934 ,2861 cm'1 v CH aliphatiques ; 2807,2767 cm'1 vCH2 N(CH2)3;1730 cm'1 vC=O ester, 1242,1227 cm'1 v C-0 éther; 848 cm'1 yCHquinoline (3R,4R)]-4-[3-(6-Méthoxyquinolin-4-yI)propyI]pipéridine-3-acétate de méthyleInfra red (CH 2 Cl 2) 2934, 2861 cm -1 CH 2 aliphatic; 2807.2767 cm -1 V CH 2 N (CH 2) 3; 1730 cm -1 C = O ester, 1242.1227 cm -1 C 0 ether; 848 cm -1 YCHquinoline (3R, 4R)] - Methyl 4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate

Un mélange de 2,8 g d’acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(tert.butyloxycarbonyl)pipéridine-3-acétique dans 100 cm3 de méthanol anhydreadditionnés d’I cm3 d’acide sulfurique à 95 % est chauffé, sous agitation, à unetempérature voisine de l’ébullition pendant 2 heures. Après refroidissement à unetempérature voisine de 20°C la masse réactionnelle est évaporée sous pression réduite(5 kPa) à une température voisine de 40°C, puis au résidu obtenu on ajoute 20 cm3d’une solution aqueuse saturée d’hydrogénocarbonate de sodium. Le mélange estextrait par 4 fois 20 cm3 de dichlorométhane. Les extraits réunis sont séchés sursulfate de magnésium, filtrés puis évaporés sous pression réduite (5 kPa) à unetempérature voisine de 40°C. On obtient 2,25 g de (3R,4R)]-4-[3-(6-méthoxyquinolin-4-yl) propyl]pipéridine-3-acétate de méthyle, sous forme d’unehuile de couleur brune. 223 1 20 2 2A mixture of 2.8 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (tert.butyloxycarbonyl) piperidine-3-acetic acid in 100 cm3 of methanol An anhydride supplemented with 1 cc of 95% sulfuric acid is heated, with stirring, to a temperature close to boiling for 2 hours. After cooling to a temperature in the region of 20 ° C., the reaction mass is evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. and 20 cm 3 of a saturated aqueous solution of sodium hydrogencarbonate are then added to the residue obtained. The mixture isextracted with 4 times 20 cm3 of dichloromethane. The combined extracts are dried over magnesium sulphate, filtered and then evaporated under reduced pressure (5 kPa) at a temperature of 40 ° C. 2.25 g of (3R, 4R)] - 4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-methyl acetate are obtained in the form of a brown oil. 223 1 20 2 2

Spectre infra rouge (CH^Cy 2954 ,2865 cm'1 v CH aliphatiques ; 2788 cm'1 v CH2N(CH2)2 ;1736 cm'1 vC=O ester; 1242,1227 cm'1 v C-0 éther; 848 cm'1 yCH quinolineInfra red spectrum (CH 2 H 2 2954, 2865 cm -1 aliphatic CH 2, 2788 cm -1 CH 2 N (CH 2) 2, 1736 cm -1 vC = O ester, 1242.1227 cm -1 C 0 ether; cm'1 yCH quinoline

Acide (3R,4R)-4-[3-(6-méthoxyquinoLin-4-yI)propyl]-l - (tertbutyloxycarbonyl)pipéridine-3-acétique A une solution de 2 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(tert.butyloxycarbonyl)pipéridine-3-acétaldéhyde dans 100 cm3 d’acétone, on ajoutesous agitation et sous atmosphère inerte à une température voisine de 20°C 1,48 g depermanganate de potassium préalablement dissous dans 45 cm3 d’eau distillée, puis220 cm3 d’acétone. Le mélange obtenu est agité pendant 2 heures à une températurevoisine de 20°C, puis après refroidissement à une température comprise entre 0 et5°C, on ajoute une solution de 5 g de sulfite de sodium dans 150 cm3 d’eau. Leprécipité brun de dioxyde de manganèse est filtré sur célite, puis l’acétone estévaporée sous pression réduite (5 kPa) à une température voisine de 40°C. On ajouteau mélange réactionnel la quantité suffisante d’acide citrique pour obtenir un pH de 4» 5. Le mélange est extrait par 2 fois 100 cm3 d’acétate d’éthyle. Les extraits réunis sontséchés sur sulfate de magnésium, filtrés puis évaporés sous pression réduite (5 kPa)*àune température voisine de 40°C. On obtient 2,8 g d’acide (3R,4R)-4-[3-(6-méthoxyquinolin-4 -yl)propyl]-1 -(tertbutyloxycarbony l)pipéridine-3-acétique, sousforme d’une meringue de couleur blanche.(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- (tertbutyloxycarbonyl) piperidine-3-acetic acid To a solution of 2 g of (3R, 4R) -4- [ 3- (6-methoxyquinolin-4-yl) propyl] -1- (tert.butyloxycarbonyl) piperidine-3-acetaldehyde in 100 cm3 of acetone, stirring is added under an inert atmosphere at a temperature in the region of 20 ° C 1, 48 g potassium depermanganate previously dissolved in 45 cm3 of distilled water, then 220 cm3 of acetone. The mixture obtained is stirred for 2 hours at a temperature of 20 ° C, then after cooling to a temperature between 0 and 5 ° C, a solution of 5 g of sodium sulphite in 150 cm3 of water is added. The brown precipitate of manganese dioxide is filtered on celite, then the acetone is evaporated under reduced pressure (5 kPa) at a temperature of 40 ° C. The sufficient amount of citric acid is added to the reaction mixture to obtain a pH of 4. The mixture is extracted with twice 100 cm3 of ethyl acetate. The combined extracts are dried over magnesium sulfate, filtered and then evaporated under reduced pressure (5 kPa) * at a temperature of 40 ° C. 2.8 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (tertbutyloxycarbonyl) piperidine-3-acetic acid are obtained, in the form of a meringue of White color.

Spectre infra rouge (KLr) 2977, 2932 ,2868 cm'1 vOH aliphatiques ; 3000-2200 cm'1v OH acide 1734 cm'1 vC=O acide; 1689 cm'1 vG:~Q eaibamale ; 1391,1365 cm'1 ÔasCH3 ; 1246 cm'1 v C-0 é(her;ll70 cm'1 v C-ü earbamate ; 848 cm'1 yCH quinoline (3R,4R)-4-[3-(6-MéthoxyquinoIin-4-yl)propyl]-l- (tert.butyloxycarbonyl)pipéridine-3-acétaldéhyde A une solution de 3,5 cm3 de chlorure d’oxalyle dans 80 cm3 de dichlorométhanerefroidie à une température voisine de -60°C, on ajoute successivement sous agitationet sous atmosphère d’azote une solution de 5,6 cm3 de diméthylsulfoxyde dissousdans 80 cm3 de dichlorométhane, puis 13,5 g de (3R,4R)-3-(2-hydroxyéthyl)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(tert.butyloxycarbonyl)pipéridine dissous dans 80cm3 de dichlorométhane, enfin 26,5 cm3 de triéthylamine dissous dans 80 cm3 dedichlorométhane. La solution obtenue est maintenue pendant 1 heure au voisinage de-60°C, puis 3 h ‘Λ à une température voisine de 20°C. Après dilution par 150 cm3 dedichlorométhane, le mélange réactionnel est lavé par 2 fois 300 cm3 d’eau. La 12 0 2 2 224 solution organique décantée est séchée sur sulfate de magnésium, filtrée, puisévaporée sous pression réduite (5 kPa) à une température voisine de 40°C. On obtient12,7 g d’une huile brune que l’on reprend par 400 cm3 d’éther diéthylique. La solutionrésultante est lavée par 2 fois 300 cm3 d’eau, puis 1 fois par 300 cm3 d’une solutionaqueuse d’acide citrique à 5 %, enfin par 2 fois 300 cm3 d’eau. La solution organiqueest séchée sur sulfate de magnésium, puis concentrée sous pression réduite (5 kPa) àune température voisine de 40°C. On obtient 7,73 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(tert.butyloxycarbonyl)pipéridine-3-acétaldéhyde,sous forme d’une gomme collante de couleur jaune.IR spectrum (KLr) 2977, 2932, 2868 cm -1 aliphatic OHV; 3000-2200 cm -1 OH acid 1734 cm -1 vC = O acid; 1689 cm -1 vG: ~ Q eaibamale; 1391.1365 cm -1 OCH 2; 1246 cm -1 C-O- (C11-Cb) -carbamate; 848 cHg quinoline (3R, 4R) -4- [3- (6-Methoxyquinin-4-yl) propyl] 1- (tert.butyloxycarbonyl) piperidine-3-acetaldehyde To a solution of 3.5 cm3 of oxalyl chloride in 80 cm3 of dichloromethane-cooled at a temperature in the region of -60 ° C. is added successively with stirring and under an atmosphere of Nitrogen solution of 5.6 cm3 of dimethylsulfoxide dissolved in 80 cm3 of dichloromethane, then 13.5 g of (3R, 4R) -3- (2-hydroxyethyl) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (tert.butyloxycarbonyl) piperidine dissolved in 80 cm3 of dichloromethane, finally 26.5 cm3 of triethylamine dissolved in 80 cm3 of dichloromethane The solution obtained is maintained for 1 hour in the vicinity of -60 ° C, then 3 hours' At a temperature in the region of 20 ° C. After dilution with 150 cm 3 of dichloromethane, the reaction mixture is washed twice with 300 cm 3 of water The organic solution which has been decanted is dried over sulphate magnesium, filtered, then evaporated under reduced pressure (5 kPa) at a temperature of 40 ° C. 12.7 g of a brown oil are obtained which is taken up in 400 cm 3 of diethyl ether. The resulting solution is washed with 2 times 300 cm3 of water, then 1 time with 300 cm3 of a 5% aqueous citric acid solution, and finally with 2 times 300 cm3 of water. The organic solution is dried over magnesium sulphate and then concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 7.73 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (tert.butyloxycarbonyl) piperidine-3-acetaldehyde are obtained in the form of a tacky gum. of yellow color.

Spectre infra rouge (CC14) 2978, 2932 ,2864 cm'1 v CH aliphatiques ;2717 cm'1 v CHaldéhyde ; 1729 cm'1 vC=O aldéhyde;1694 cm'1 vC=O carbamate ; 1391,1366 cm'1 ôasCH3 ; 1242 cm'1 v C-0 éther; 1158 cm'1 v C-0 carbamate ; 844 cm'1 yCH quinoline (3R,4R)-3-(2-Hydroxyéthyl)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l- (terubutyloxycarbonyl)pipéridineInfra red spectrum (CCl 2) 2978, 2932, 2864 cm -1 aliphatic CH 2, 2717 cm -1 CH 3 aldehyde; 1729 cm -1 vC = O aldehyde; 1694 cm -1 vC = O carbamate; 1391.1366 cm -1 δasCH3; 1242 cm -1 C 0 ether; 1158 cm -1 C-O carbamate; 844 cm -1 yCH quinoline (3R, 4R) -3- (2-hydroxyethyl) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (terubutyloxycarbonyl) piperidine

Une solution de 2 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l- (tert.butyloxycarbonyl)-3-vinylpipéridine et de 0,72 cm3 de triéthylamine borane dans 10 cm3 de toluène est agitée sous atmosphère inerte à une température voisine de 110°C pendant 10 heures. La masse réactionnelle est concentrée à sec sous pression réduite (5 kPa) à une température voisine de 60°C. On obtient 2,1 g d'une meringue de couleur orangée que l’on solubilise dans 9 cm3 d’acétone et auxquels on ajoute 1,9 cm3 d’acide chlorhydrique aqueux à 5 %. Après agitation du mélange pendant 20 minutes à une température voisine de 20°C, la masse réactionnelle est concentrée sous pression réduite (5 kPa) à une température voisine de 40°C. Le résidu obtenu est repris par 7,5 cm3 de tétrahydrofuranne, 6,2 cm3 de soude aqueuse à 30 % et 7,5 cm3 de peroxyde d’hydrogène en solution aqueuse à 30 %. Le mélange est chauffé pendant 3 heures à une température voisine du reflux. Après refroidissement, le mélange réactionnel est agité avec 30 cm3 de chloroforme à une température voisine de 20°C.A solution of 2 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (tert.butyloxycarbonyl) -3-vinylpiperidine and 0.72 cm3 of triethylamine borane in 10 cm3 of toluene is stirred under an inert atmosphere at a temperature of 110 ° C for 10 hours. The reaction mass is concentrated to dryness under reduced pressure (5 kPa) at a temperature in the region of 60 ° C. 2.1 g of an orange meringue are obtained which is solubilized in 9 cm3 of acetone and to which 1.9 cm3 of 5% aqueous hydrochloric acid is added. After stirring the mixture for 20 minutes at a temperature in the region of 20 ° C., the reaction mass is concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. The residue obtained is taken up in 7.5 cm 3 of tetrahydrofuran, 6.2 cm 3 of 30% aqueous sodium hydroxide and 7.5 cm 3 of hydrogen peroxide in aqueous solution at 30%. The mixture is heated for 3 hours at a temperature close to reflux. After cooling, the reaction mixture is stirred with 30 cm3 of chloroform at a temperature in the region of 20 ° C.

La phase aqueuse est décantée ; la phase organique est lavée par 3 fois 30 cm3 d’eau, puis 1 fois 20 cm3 d’une solution saturée de chlorure de sodium. Après séchage sur sulfate de magnésium la solution organique est concentrée sous pression réduite (5 kPa) à une température voisine de 40QC. On obtient 1,7 g d’une huile de couleur jaune-brun que l’on purifie par chrorriatographie à pression atmosphérique sur une colonne de gel de silice (granulométrie 40-63 μ ; diamètre 3,5 cm ; masse 60 g) en\ éluant par un mélange de dichlorométhane-méthanol (95/5 en volumes) et en 225 120 2 2 recueillant des fractions de 20 cm3. Les fractions 4 et 5 sont réunies, évaporées souspression réduite (5 kPa) à une température voisine de 40°C. On obtient 0,95 g de(3R,4R)-3-(2-hydroxyéthyl)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(tert.butyloxy-carbonyl)pipéridine, sous forme d’une meringue de couleur jaune-orangé.The aqueous phase is decanted; the organic phase is washed with 3 times 30 cm3 of water, then 1 time 20 cm3 of a saturated solution of sodium chloride. After drying over magnesium sulphate, the organic solution is concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 1.7 g of a yellow-brown oil are obtained, which is purified by chromatography at atmospheric pressure on a column of silica gel (particle size 40-63 μ, diameter 3.5 cm, mass 60 g) in eluent with a mixture of dichloromethane-methanol (95/5 by volume) and 225 120 2 2 collecting fractions of 20 cm3. Fractions 4 and 5 are combined and evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 0.95 g of (3R, 4R) -3- (2-hydroxyethyl) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (tert.-butyloxycarbonyl) piperidine is obtained. form of a yellow-orange meringue.

Spectre infra rouge (KBr) 3550-3100 cm'1 v OH alcool ; 2972, 2931, 2865 cm'1 v CHaliphatiques ; 1690 cm'1 vC=O carbamate ; 1391,1365 cm'1 5as CH3 ; 1244,1228 cm'1 vC-0 éther ;1158 cm*1 v C-0 carbamate ; 103 lcm"1 v C-0 alcool; 845 cm'1 yCHquinoline (3R,4R)-4-[3-(6-Méthoxyquinolin-4-yl)propyI]-rÎ-(tertbutyIoxycarbonyl)-3- vinylpipéridine A une suspension de 5 g de chlorhydrate de (3R,4R)-4-[3-(6-méthoxyquinolin-4-ÿl)propyl]-3-vinylpipéridine dans 50 cm3 de dichlorométhane, on ajoute sousagitation à une température voisine de 20°C 4 cm3 de triéthylamine, puis 3,15 g dedi-tertiobutyl dicar’oonate. Après 45 minutes la solution obtenue est lavée par 2 fois30 cm3 d’eau, séchée sur sulfate de magnésium puis concentrée sous pression réduite(5 kPa) à une température voisine de 40°C. On obtient 6 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(tert.butyloxycarbonyl)-3-vinylpipéridine, sousforme d’une huile de couleur brune.Infrared spectrum (KBr) 3550-3100 cm -1 alcohol; 2972, 2931, 2865 cm -1 CHaliphatics; 1690 cm -1 vC = O carbamate; 1391, 1365 cm-1 5as CH3; 1244.1228 cm -1 vC-O ether; 1158 cm -1 C-O carbamate; 103 lcm -1 C-0 alcohol; 845 cm -1 H -quinoline (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -rn- (tertbutyloxycarbonyl) -3-vinylpiperidine has a suspension 5 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -3-vinylpiperidine hydrochloride in 50 cm 3 of dichloromethane are added under stirring at a temperature in the region of 20 ° C. 4 cm 3 of triethylamine and then 3.15 g of di-tert-butyl dicarboxione After 45 minutes the solution obtained is washed with twice 30 cm3 of water, dried over magnesium sulphate and then concentrated under reduced pressure (5 kPa) at a similar temperature. at 40 ° C. 6 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (tert.-butyloxycarbonyl) -3-vinylpiperidine are obtained in the form of an oil. brown in color.

Spectre infra rouge (CII2C17) 2972, 2933, 2860 cra'1 v Cil aliphatiques ; 1680 cra'1vOO carbamate ; i391,1365 cm'1 δ„ CH3 ;]244J228 cm'1 v C-0 éther ',1165 cm'1 vC-0 carbamate ; 845 c-m'1 yCH quinolineInfra red spectrum (CII2C17) 2972, 2933, 2860 Aliphatic Cil; 1680 carbamate carbamate; 1 391, 1365 cm -1, δ "CH 3;] 244 J 228 cm -1 C 0 ether, 1165 cm -1 vC-O carbamate; 845 c-m'1 yCH quinoline

Le chlorhydrate de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-3-vinylpipéridinepeut être obtenu par application de la méthode décrite dans la demande de brevet FR2 354 771.(3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -3-vinylpiperidine hydrochloride can be obtained by applying the method described in patent application FR 2 354 771.

Exemple 37Example 37

Dichlorhydrate de l’acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yI)propyl]-l-[2-(cyclohexylthio)éthyIjpipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl) piperidine-3-acetic acid dihydrochloride

Un mélange de 0,3 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yI)propyl]-l-[2-(cyclohexylthio)éthyl]pipéridine-3-acétate de méthyle dans 8 cm3 de dioxanne enprésence de 0,5 cm3 de soude aqueuse 5N est chauffée sous agitation à unetempérature voisine de 60°C pendant 20 heures. Après refroidissement à une 226 120 2 2 température voisine de 20°C, le mélange réactionnel est évaporé sous pression réduite(5 kPa) à une température voisine de 40°C. On obtient une meringue de couleur jauneque l’on purifie par chromatographie à pression atmosphérique sur une colonne de gelde silice (granulométrie 20-45μ ; diamètre 1,6 cm ; volume silice 40 cm3) en éluantpar un mélange de chloroforme-méthanol-ammoniaque à 28 % (12/3/0,5 en volumes)et en recueillant d’abord une fraction de 125 cm3, puis des fractions d’environ 10 cm3.Les fractions 3 à 7 sont réunies puis évaporées sous pression réduite (5 kPa) à unetempérature voisine de 40°C. On obtient 0,27 g d’une laque que l’on reprend par5 cm3 de dioxanne, 11 cm3 .d’acide chlorhydrique aqueux 0,lN et 14 cm3 d’eaudistillée. Le dioxanne est évaporé sous pression réduite (5 kPa) à une températurevoisine de 40°C, puis la solution résiduelle est lyophilisée. On obtient 0,29 g dedichlorhydrate de l’acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(cyclohexylthio)éthyl]pipéridine-3-acétique, sous forme d’un lyophilisât de couleurblanche.A mixture of 0.3 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperidine-3-methyl acetate in 8 g. cm3 of dioxane in presence of 0.5 cm3 of 5N aqueous sodium hydroxide is heated with stirring at a temperature of 60 ° C for 20 hours. After cooling to a temperature close to 20 ° C., the reaction mixture is evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. A meringue of yellow color is obtained which is purified by chromatography at atmospheric pressure on a silica gel column (particle size 20-45 μ, diameter 1.6 cm, silica volume 40 cm 3), eluting with a mixture of chloroform-methanol-aqueous ammonia. 28% (12/3 / 0.5 by volume) and firstly collecting a fraction of 125 cm 3, then fractions of approximately 10 cm 3. Fractions 3 to 7 are combined and then evaporated under reduced pressure (5 kPa) at a temperature close to 40 ° C. 0.27 g of a lacquer is obtained, which is taken up in 5 cm3 of dioxane, 11 cm3 of 0.1N aqueous hydrochloric acid and 14 cm3 of water-distilled water. The dioxane is evaporated under reduced pressure (5 kPa) at a temperature of 40 ° C, then the residual solution is freeze-dried. 0.29 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (2- (cyclohexylthio) ethyl] piperidine-3-acetic acid dihydrochloride is obtained, in the form of a lyophilisate of white color.

Spectre de R.M.N. (400 MHz, (CD3)2SO d6 à une température de 383K, δ enppm) : de 1,25 à 2,05 (mt : 18H) ; 2,33 (dd, J = 16 et 5,5 Hz : ÎH); de 2,50 à 2,60(mt : 1H) ; 2,83 (mt : 1H) ; de 2,95 à 3,30 (mt : 10H) ; 4,00 (s : 3H) ; 7,45 (d, J = 5Hz : 1H) ; 7,48 (d, J = 2 Hz : 1H) ; 7,51 (dd, J = 9,5 et 2 Hz : IH) ; 8,08 (d, J = 9,5Hz : 1H) ; 8,72 (d, J = 5 Hz : 1H). (3R,4R)-4-[3-(6-Méthoxyquinolin-4-yl)propyl]-l-[2- (cyclohexyIthio)éthyl]pipéridine-3-acétate de méthyleSpectrum of R.M.N. (400 MHz, (CD3) 2SO d6 at a temperature of 383K, δppm): from 1.25 to 2.05 (mt: 18H); 2.33 (dd, J = 16 and 5.5 Hz: 1H); from 2.50 to 2.60 (mt: 1H); 2.83 (mt: 1H); from 2.95 to 3.30 (mt: 10H); 4.00 (s: 3H); 7.45 (d, J = 5Hz: 1H); 7.48 (d, J = 2 Hz: 1H); 7.51 (dd, J = 9.5 and 2 Hz: 1H); 8.08 (d, J = 9.5 Hz: 1H); 8.72 (d, J = 5 Hz: 1H). Methyl (3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperidine-3-acetate

Un mélange de 1,2 g de (3R,4R)]-4-[3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-acétate de méthyle, 0,65 g de 2-chloroéthylcyclohexyl sulfure dans 25 cm3d’acétonitrile additionnés de 2,3 g de carbonate de potassium et 0,55 g d’iodure depotassium est chauffé sous agitation et sous atmosphère inerte à une températurevoisine de 80°C pendant 4 heures. Après refroidissement à une température voisine de20°C, le mélange réactionnel est additionné de 30 cm3 d’eau puis extrait par 2 fois200 cm3 d’acétate d’éthyle. Les extraits organiques réunis sont lavés par 2 fois 40 cm3d’acide chlorhydrique aqueux N. Après décantation les extraits acides réunis sontalcalinisés par une solution aqueuse saturée d’hydrogénocarbonate de sodium, puisextraits par 2 fois 100 cm3d’acétate d’éthyle. Les extraits organiques sont réunis,séchés sur sulfate de magnésium, filtrés, évaporés sous pression réduite (5*kPa) à unetempérature voisine de 40°C. On obtient 0,80 g d’une huile brune que l’on purifie parchromatographie sous pression atmosphérique sur une colonne de gel de silice 227 120 22 (granulométrie 20-45μ ; diamètre 2,5 cm ; volume silice 120 cm3) en éluant d’abordpar un mélange de dichlorométhane-méthanol (99/1 en volumes) et en recueillantd’abord une fraction de 250 cm3, puis en éluant par un mélange de dichlorométhane-méthanol (90/1 en volumes) et en recueillant une fraction de 200 cm3. On élue ànouveau par un mélange de dichlorométhane-méthanol (99/1 en volumes) et l’onrecueille des fractions d’environ 10 cm3. Les fractions 10 à 33 sont réunies puisconcentrées sous pression réduite (5 kPa) à une température voisine de 40°C. Onobtient 0,30 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(cyclohexyl-thio)éthyl]pipéridine-3-acétate de méthyle, sous forme d’une huile incolore.A mixture of 1.2 g of (3R, 4R)] - methyl 4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate, 0.65 g of 2-chloroethylcyclohexyl sulfide in 25 g. cm 3 of acetonitrile supplemented with 2.3 g of potassium carbonate and 0.55 g of potassium iodide is heated with stirring and under an inert atmosphere at a temperature of 80 ° C for 4 hours. After cooling to a temperature of 20 ° C, the reaction mixture is added with 30 cm3 of water and then extracted with 2 times 200 cm3 of ethyl acetate. The combined organic extracts are washed with twice 40 cm3 of aqueous hydrochloric acid N. After decantation, the combined acid extracts are alkalized with a saturated aqueous solution of sodium hydrogencarbonate, twice per 100 cm3 of ethyl acetate. The organic extracts are combined, dried over magnesium sulphate, filtered and evaporated under reduced pressure (5 * kPa) at a temperature in the region of 40 ° C. 0.80 g of a brown oil is obtained which is purified by chromatography under atmospheric pressure on a column of silica gel 227 120 22 (particle size 20-45 μ, diameter 2.5 cm, silica volume 120 cm 3), eluting d firstly a mixture of dichloromethane-methanol (99/1 by volume) and first collecting a fraction of 250 cm 3, then eluting with a mixture of dichloromethane-methanol (90/1 by volume) and collecting a fraction of 200 cm3. It is eluted again with a mixture of dichloromethane-methanol (99/1 by volume) and fractions of about 10 cm3 are collected. Fractions 10 to 33 are pooled under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 0.30 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperidine-3-acetate are obtained. form of a colorless oil.

Spectre infra rouge (CC14) 2932,2855 cm'1 v CH aliphatiques ;2800,2763 cm"1 v CH2N(CH2)3;1737 cm·1 v C-0 ester ;1241,1227 cm’1 v C-0 éther; 844 cm"1 yCHquinolineInfrared spectrum (CCl 2) 2932.2855 cm -1 CH 2 aliphatic; 2800.2763 cm -1 CH 2 N (CH 2) 3; 1737 cm -1 C-O ester; 1241.1227 cm -1 C 0 ether 844 cm -1 y CHquinoline

Le (3R,4R)]-4-[3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-acétate de méthylepeut être préparé comme décrit à l’exemple 36.(3R, 4R)] - Methyl 4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate may be prepared as described in Example 36.

Exemple 38Example 38

Dichlorhydrate de l’acide (3R,4R)-4-(3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2-thiénylthio)éthyl]pipéridine-3-carboxylique.(3R, 4R) -4- (3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] dihydrochloride piperidine-3-carboxylic acid.

Une solution de 0,2 g de (3R54R)-4~[3"(R,S)-fiuoro-.3-(6-rnùboxyquinolin-4-yî)propyl]-l·[2~(2-drénylthie)éthyiJj.>ipcrîdinc-3-frîrboxy3ate de méthyle dans 3 cm3d’acide chlorhydrique aqueux 6N est chauffée sous agitation à une températurevoisine de J 00°C pendant 7 heures, puis évaporée sous pression réduite (5 kPa) à unetempérature voisine de 50°C. Le résidu obtenu est agité dans 10 cm3 d’étherdiisopropylique. Les cristaux qui en résultent sont filtrés, lavés par 2 fois 5 cm3d’éther diisopropylique, séchés sous pression réduite (13 Pa) à une températurevoisine de 60°C. On obtient 0,22 g de dichlorhydrate de l’acide (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl)-1-(2-(2-thiénylthio)éthyl]pipéridine-3-carboxylique, sous forme d’un solide de couleur beige fondant en se ramollissant àune température voisine de 140°C.A solution of 0.2 g of (3R54R) -4- [3 "(R, S) -fluoro-β- (6-fluoroxyquinolin-4-yl) propyl] -1- [2 - (2-drenylthia) ethyl ether in 3 cm 3 of 6N aqueous hydrochloric acid is heated with stirring to a temperature of about 00 ° C. for 7 hours and then evaporated under reduced pressure (5 kPa) at a temperature in the region of 50 ° C. The residue obtained is stirred in 10 cm3 of diisopropyl ether, the resulting crystals are filtered off, washed with twice 5 cm 3 of diisopropyl ether and dried under reduced pressure (13 Pa) at a temperature of 60 ° C. 22 g of (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl) -1- (2- (2- (2- (2- (4 -) -hydroxybenzyl) -2-dihydrochloride salt. thienylthio) ethyl] piperidine-3-carboxylic acid, in the form of a beige-colored solid melting while softening at a temperature in the region of 140 ° C.

Spectre de R.M.N. (400 MHz, (CD,)2SO d6 avec ajout de quelques gouttes deCD3COOD d4, à une température de 373K, δ en ppm). On observe un mélange dedeux diastéréoisomères : 228 12022 de 1,55 à 2,30 et de 3,10 à 3,50 (mts : 15H) ; 3,10 (s large : 1H) ; 3,98 (s : 3H) ; 6,31(mt, JHF = 48 Hz : 1H) ; 7,10 (mt : 1H) ; 7,29 (d large, J = 4 Hz : 1H) ; de 7,35 à 7,45(rat : 1H) ; de 7,45 à 7,60 (mt : 2H) ; 7,64 (d large, J = 5,5 Hz : 1 H) ; 8,06 (d, J = 9Hz : 1H) ; 8,82 (d, J = 5 Hz : 1H). (3R,4R)-4-[3-(R,S)-Fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2-thiénylthio)éthyl]pipéridine-3-carboxylate de méthyle. A une solution agitée de 0,5 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin- 4-yl)propyl]-l-[2-(2-thiénylthio)éthyl]pipéridine-3-carboxylate de méthyle dans 8 cm3de dichlorométhane, refroidie à une température voisine de 10°C, on ajoute sousatmosphère inerte 0,16 cm3 de diéthylaminosulfure trifluorurè dissous dans 2 cm3 dedichlorométhane. Après 10 minutes d’agitation à cette température, on laisse revenir àune température voisine de 20°C et l’on poursuit l’agitation pendant 18 heures. Aprèsaddition de 8 cm3 d’une solution aqueuse saturée d’hydrogénocarbonate de sodium etagitation pendant 15 minutes, la phase organique est décantée. La phase aqueuse estextraite 1 fois par 5 cm3 de dichlorométhane, puis les extraits organiques sont réunis,séchés sur sulfate de magnésium, filtrés, évaporés sous pression réduite (5 kPa) à unetempérature voisine de 40°C. On obtient 0,5 g d’une huile rouge que l’on purifie parchromatographie sous une pression de 100 kPa d’azote sur une colonne de gel desilice (granulométrie 40-63μ ; diamètre 3,5 cm ; hauteur silice 35 cm), en éluant parun mélange de dichlorométhane-méthanol (97,5/2,5 en volumes), et en recueillant desfractions de 30 cm3. On réunit les fractions 25 à 29 que l’on évapore sous pressionréduite (5 kPa) à une température voisine de 40°C. On obtient 0,2 g de (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2-thiénylthio)éthyl]pipéridine-3-carboxylate de méthyle, sous forme d’une huile de couleur orangée.Spectrum of R.M.N. (400 MHz, (CD,) 2SO d6 with addition of a few drops ofCD3COOD d4, at a temperature of 373K, δ in ppm). A mixture of two diastereoisomers is observed: from 1.55 to 2.30 and from 3.10 to 3.50 (mts: 15H); 3.10 (brs: 1H); 3.98 (s: 3H); 6.31 (mt, JHF = 48 Hz: 1H); 7.10 (mt: 1H); 7.29 (broad d, J = 4 Hz: 1H); from 7.35 to 7.45 (rat: 1H); from 7.45 to 7.60 (mt: 2H); 7.64 (broad d, J = 5.5 Hz: 1H); 8.06 (d, J = 9Hz: 1H); 8.82 (d, J = 5 Hz: 1H). (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -l- [2- (2-thienylthio) ethyl] piperidine-3-carboxylate of methyl. To a stirred solution of 0.5 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2) Methyl-thienylthio) ethyl] piperidine-3-carboxylate in 8 cm3 of dichloromethane, cooled to a temperature of 10 ° C, 0.16 cm3 of diethylaminosulfide trifluoride dissolved in 2 cm3 of dichloromethane are added inert atmosphere. After stirring for 10 minutes at this temperature, it is allowed to return to a temperature in the region of 20 ° C. and stirring is continued for 18 hours. Afteraddition of 8 cm3 of a saturated aqueous solution of sodium hydrogencarbonate and stirring for 15 minutes, the organic phase is decanted. The aqueous phase isextracted once with 5 cm3 of dichloromethane, then the organic extracts are combined, dried over magnesium sulphate, filtered and evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 0.5 g of a red oil is obtained which is purified by chromatography under a pressure of 100 kPa of nitrogen on a desilice gel column (particle size 40-63 μ, diameter 3.5 cm, silica height 35 cm), eluting with a mixture of dichloromethane-methanol (97.5 / 2.5 by volume), and collecting fractions of 30 cm3. Fractions 25 to 29 are combined and evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 0.2 g of (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio)) are obtained. methyl] piperidine-3-carboxylate methyl, in the form of an orange-colored oil.

Spectre infra rouge (CC14) 2950 cm'1 v CH aliphatiques ;2804,2767 cm'1 v CH2N(CH2)3 ;1737 cm'1 v C=O ester ; 1243,1229 cm'1 v C-0 éther; 852 cm'1 yCHquinolineInfra red spectrum (CCl 2) 2950 cm -1 CH 2 aliphatic; 2804.2767 cm -1 CH 2 N (CH 2) 3; 1737 cm -1 C = O ester; 1243.1229 cm -1 C 0 ether; 852 cm'1 yCHquinoline

Exemple 39Example 39

Dichlorhydrate de l’acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-* (thién-2-yl)prop-2-ynyl]pipéridine-3-acétique. A une solution agitée de 0,43 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thién-2-yl)prop-2-ynyl]pipéridine-3-acétate de méthyle dans 10 cm3 de dioxanne, 120 2 2 229 sous atmosphère inerte, on ajoute 0,8 cm3 d’une solution aqueuse de soude 5N. Lemélange est chauffé pendant 20 heures à une température voisine de 60°C, puis aprèsrefroidissement à une température voisine de 20°C, le mélange réactionnel estévaporé sous pression réduite (5 kPa) à une température voisine de 45°C. On obtient0,8 g d’un produit que l’on purifie par chromatographie à pression atmosphérique surune colonne de gel de silice· (granulométrie 20-45μ ; diamètre 3 cm ; hauteur silice 30cm) en éluantpar un mélange de chloroforme-méthanol-ammoniaque à 28% (12/3/0,5en volumes) et en recueillant des fractions de 25 cm3. Les fractions 14 à 29 sontréunies puis évaporées sous pression réduite (5 kPa) à une température voisine de40°C. On obtient 0,350 g d’un solide blanc dont on fait le chlorhydrate de la façonsuivante : le solide obtenu est dissous dans 5 cm3 de dichlorométhane, puis la solutionobtenue est ajoutée sous agitation et sous atmosphère inerte à 10 cm3 d’étherchlorhydrique IN. Le mélange est dilué par 100 cm3 d’éther anhydre. On obtient unesuspension blanche que l’on agite pendant 3 heures à une température voisine de20°C. Les cristaux sont filtrés, lavés par 5 fois 10 cm3 d’éther diéthylique, séchés souspression partielle (10 Pa) à une température voisine de 20°C. On obtient 0,430 g dedichlorhydrate de l’acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thién-2-yl)prop-2-ynylj pipéridine-3-acétique, sous forme d’un solide blanc fondant endevenant pâteux et se décomposant au voisinage de 180°C.(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-3-dihydrochloride -acetic. To a stirred solution of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl) (0.43 g) ] Piperidine-3-methyl acetate in 10 cm3 of dioxane, under an inert atmosphere, 0.8 cm3 of a 5N aqueous sodium hydroxide solution. The mixture is heated for 20 hours at a temperature in the region of 60 ° C. and then after cooling to a temperature in the region of 20 ° C., the reaction mixture is evaporated under reduced pressure (5 kPa) at a temperature in the region of 45 ° C. 0.8 g of a product which is purified by chromatography at atmospheric pressure on a column of silica gel · (particle size 20-45μ, diameter 3 cm, silica height 30 cm) eluting with a mixture of chloroform-methanol-ammonia at 28% (12/3 / 0.5in volumes) and collecting fractions of 25 cm3. Fractions 14 to 29 are combined and then evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 0.350 g of a white solid is obtained, the hydrochloride of which is prepared as follows: the solid obtained is dissolved in 5 cm of dichloromethane, and then the solution obtained is added with stirring and under an inert atmosphere to 10 cm3 of 1 N hydrochloric acid. The mixture is diluted with 100 cm3 of anhydrous ether. A white suspension is obtained which is stirred for 3 hours at a temperature in the region of 20 ° C. The crystals are filtered, washed with 5 times 10 cm3 of diethyl ether, dried under partial pressure (10 Pa) at a temperature in the region of 20 ° C. 0.430 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine dihydrochloride is obtained. -3-acetic acid, in the form of a white solid melting in pasty pasty and decomposing in the vicinity of 180 ° C.

Spectre de R.M.N. (400 MHz, (CD,)?SO d6, δ en ppm) : de 1.35 à 3,80 (mis :1611) ; 4,00 (s : 3H) ; 4,38 et 4,43 (infs : 2H en totalité) ; 7,16 (ml : 1H) ; 7,46 (d, J = 3.5 Hz : JB) ; 7,53 (rot : 3.H) ; 7,64 (int : 2B) ; 7,74 (d, J - 5 Hz : ÎH) ; 8,12 (d, J = 9.5 Hz : ÏH) ; 8,86 (mf : Π1) ; 9,95 ci 10,45 (7in;s étalés : 111 en totalité) ; de 12,20 à 12,55 (rnf étalé : 1H). (3R,4R)-4-[3-(6-lViéthoxyquÎnoIm-4-yI)propyI]-l-[3-(thién-2-yI)prop-2-ynyl]pipéridine-3-acétate de méthyle A une solution agitée de 0,44 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(prop-2-ynyl)pipéridine-3-acétate de méthyle dans 15 cm3 d’acétonitrile anhydre, sousatmosphère inerte, on ajoute à une température voisine de 20°C 0,027 g detriphénylphosphinc, 0,091 g de tétrakis(triphénylphosphine)palladium, puis 0,044 gd’iodure cuivreux. Après 15 minutes d’agitation de la solution obtenue on ajoute0,2 cm3de 2-iodothiophène et 0,32 cm3 de triéthylamine. Après 12 heures d’agitation àune température voisine de 20°C, le mélange réactionnel est filtré sur célite, puis legâteau est lavé par 5 fois 10 cm3 d’acétonitrile. Les extraits organiques réunis sont 230 1 20 22 évaporés sous pression réduite (5 kPa) à une température voisine de 40°C. On obtient1,1g d’une huile que l’on purifie par chromatographie à pression atmosphérique surune colonne de gel de silice (granulométrie 20-45μ ; diamètre 4 cm ; hauteur silice28 cm) en éluant par l’acétate d’éthyle et en recueillant des fractions de 30 cm3. Lesfractions 14 à 27 sont réunies puis évaporées sous pression réduite (5 kPa) à unetempérature voisine de 40°C. On obtient 0,430 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propylj-1 -[3-(thién-2-yl)prop-2-ynylJpipéridine-3-acétate deméthyle, sous forme d’une huile visqueuse de couleur jaune.Spectrum of R.M.N. (400 MHz, (CD,)? SO d6, δ in ppm): from 1.35 to 3.80 (mis: 1611); 4.00 (s: 3H); 4.38 and 4.43 (all infs: 2H); 7.16 (ml: 1H); 7.46 (d, J = 3.5 Hz: JB); 7.53 (rot: 3.H); 7.64 (int: 2B); 7.74 (d, J - 5 Hz: 1H); 8.12 (d, J = 9.5 Hz: H); 8.86 (mf: Π1); 9.95 and 10.45 (7in; s spread: 111 in total); from 12.20 to 12.55 (extended rnf: 1H). Methyl (3R, 4R) -4- [3- (6-yl) ethoxyquinoro-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-3-acetate. stirred solution of 0.44 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-methyl acetate in 15 cm3 anhydrous acetonitrile, inert subatmosphere, 0.027 g of triphenylphosphine, 0.091 g of tetrakis (triphenylphosphine) palladium and then 0.044 g of cuprous iodide are added at a temperature in the region of 20 ° C. After stirring for 15 minutes, 0.2 cm 3 of 2-iodothiophene and 0.32 cm 3 of triethylamine are added. After stirring for 12 hours at a temperature in the region of 20 ° C., the reaction mixture is filtered through Celite, and then the cake is washed with 5 times 10 cm3 of acetonitrile. The combined organic extracts are evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 1.1 g of an oil which is purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45 μ, diameter 4 cm, silica height 28 cm) eluting with ethyl acetate and collecting fractions of 30 cm3. Fractions 14 to 27 are combined and then evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 0.430 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-3-acetate-methyl are obtained, in the form of a viscous yellow oil.

Spectre infra rouge (CH2C12) 2936,2862 cm'1 v CH aliphatiques ;2806,2763 cm'1 vCH2 N(CH2)3;1731 cm'1 v C=O ester ; 1242,1227cm'1 v C-0 éther; 848 cm'1 yCHquinoline (3R,4R)-4-[3-(6-Méthoxyquinonn-4-yI)propyI]-l-(prop-2-ynyl)pipéridine-3-acétate de méthyle A une solution agitée de 0,8 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-acétate de méthyle dans 15 cm3 de diméthylformamide anhydre,sous atmosphère inerte, on ajoute à une température voisine de 20°C 1,28 cm3 detriéthylamine, puis 0,26 cm3 de bromure de propargyle à 97 %. Le mélange est porté àune température voisine de 45°C pendant 6 heures, puis refroidi à environ 20°C.Après dilution par 150 cm3 d’eau le mélange est extrait par 5 fois 50 cm3 d’acétated’éthyle. Les extraits réunis sont lavés par 3 fois 50 cm3 d’eau, séchés sur sulfate demagnésium, filtrés, concentrés sous pression réduite (5 kPa) à une température voisinede 40°C. On obtient 1 g d’un résidu huileux que l’on purifie par chromatographiesous pression atmosphérique, sur une colonne de gel de silice (granulométrie 20-45 μ; diamètre 3 cm ; hauteur silice 27 cm) en éluant par de l’acétate d’éthyle pur. Onrecueille des fractions de 50 cm3. Les fractions 7 à 10 sont réunies puis évaporéessous pression réduite (5 kPa) à une température voisine de 40°C. On obtient 0,45 g de(3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(prop-2-ynyI)pipéridine-3-acétatede méthyle, sous forme d’une huile visqueuse incolore.Infra red (CH 2 Cl 2) 2936.2862 cm -1 CH 2 aliphatic; 2806.2763 cm -1 VCH 2 N (CH 2) 3; 1731 cm -1 C = O ester; 1242.1277 cm -1 C 0 ether; 848 cm -1 Methylquinoline (3R, 4R) -4- [3- (6-Methoxyquinonn-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-methyl acetate To a stirred solution of 8 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-methyl acetate in 15 cm3 of anhydrous dimethylformamide, under an inert atmosphere, are added at a similar temperature. of 20 ° C., 1.28 cm3, triethylamine and then 0.26 cm3 of 97% propargyl bromide. The mixture is brought to a temperature of 45 ° C for 6 hours and then cooled to about 20 ° C. After dilution with 150 cm3 of water the mixture is extracted with 5 times 50 cm3 of ethyl acetate. The combined extracts are washed with water (3 × 50 cc), dried over magnesium sulphate, filtered and concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 1 g of an oily residue is obtained, which is purified by chromatography under atmospheric pressure, on a column of silica gel (particle size 20-45 μ, diameter 3 cm, silica height 27 cm), eluting with sodium acetate. pure ethyl. Fractions of 50 cm3 are collected. Fractions 7 to 10 are combined and then evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 0.45 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-acetated methyl are obtained in the form of a viscous, colorless oil.

Spectre infra rouge (CH,C12) 3302 cm'1 v CH acétylénique ; 2936,2863 cm'1 v CHaliphatiques ; 2808,2764 cm'1 v CH2 N(CH2)3 ; 1731 cm'1 v C=O ester ;1242 ; 1227 cm' 1 v C-O éther ; 848 cm'1 yCH quinolineInfra red spectrum (CH, C12) 3302 cm -1 acetylenic CH; 2936,2863 cm -1 CHaliphatics; 2808.2764 cm -1 CH 2 N (CH 2) 3; 1731 cm -1 C = O ester, 1242; 1227 cm -1 C-O ether; 848 cm -1 yCH quinoline

Le (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-acétate de méthyle aété préparé selon le mode opératoire décrit dans l’exemple 36. 231Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate was prepared according to the procedure described in Example 36. 231

Exemple 40Example 40

Dichlorhydrate de l’acide (3R,4R)-4-[3-hydroxy-3-(6-méthoxyquinoIin-4-yl)propyI]-l-[2-(cycIohepiylthio)éthyI]pipéridine-3-carboxyIique,diastéréoisomère A et .dichlorhydrate de l’acide (3R,4R)-4-[3-hydroxy-3-(6-méthoxyquinolin-4-yl)propyI]-l-[2-(cycIoheptyIthio)éthyl]pipéridine-3-carboxylique, diastéréoisomère B.(3R, 4R) -4- [3-Hydroxy-3- (6-methoxyquinin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperidine-3-carboxylic acid dihydrochloride, diastereoisomer A and (3R, 4R) -4- [3-Hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (2- (cycloheptylthio) ethyl] piperidine-3-carboxylic acid dihydrochloride, diastereoisomer B.

Un mélange de 1,8 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyqüinolin-4-yl)propyl]-l-[2-(cycIoheptylthio)éthyl]pÎpéridine-3-carboxylate de méthyle dans36 cm3 de dioxanne avec 2,8 cm3 de soude aqueuse 5N est chauffé pendant 24 heuresà une température voisine de 60°C. Après refroidissement du mélange réactionnel àune température voisine de 20°C, puis concentration sous pression réduite (5 kPa) àune température voisine de 40°C, le résidu obtenu est purifié par chromatographiesous pression atmosphérique sur une colonne de gel de silice (granulométrie 20-45μ ;diamètre 4 cm ; masse 180 g) en éluant par un mélange de dichlorométhane-méthanol-ammoniaque à 28 % (40/5/0,5 en volumes) et en recueillant des fractions de50 cm3. On obtient 3 lots que l’on évapore sous pression réduite (5 kPa) à unetempérature voisine de 40°C : le lot A (0,48 g) correspondant au diastéréoisomère A ;le lot B (0,6 g) correspondant au diastéréoisomère B ; le lot C (0,5 g) correspondant àun mélange des deux diastéréoisomères. Le lot A est purifié dé la façon suivante :après dissolution dans 15 cm3 de dichlorométhane et addition à 10 cm3 d’étherdiéthylique chlorhydrique N, le mélange gommeux obtenu est évaporé sous pressionréduite (5 kPa) à une température voisine, de 40°C. Api es reprise du résidu par 40 cm3d’acétonitrile et 2 cm3 d’acide chlorhydrique 0,5 N, la solution obtenue est évaporéedans les mêmes conditions que ci-dessus. On obtient un solide blanc que l’on sèchependant 16 heures sous pression réduite (vide phosphorique, 5 kPa). Après agitationdans 100 cm3 d’éther diéthylique puis filtration, on obtient 0,514 g de dichlorhydratede l‘acide (3 R,4R)-4-[3-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(cyclo-heptylthio)éthyl]pipéridine-3-carboxylique, diastéréoisomère A. (aD2°=-58,3°+/-l,00,dans le méthanol à 0,5%), sous forme d’un solide de couleur blanche. Les lots B et Csont traités de la même façon. On obtient, en particulier avec le lot B, 0,650 g dedichlorhydrate de l’acide (3R,4R)-4-[3-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(cycloheptylthio)éthyl]pipéridine-3-carboxylique, diastéréoisomère B.(aD20=+120,4o+/-l ,7, dans le méthanol à 0,5 %), sous forme d’un solide de couleurblanche. 120 2 2 232 diastéréoisomère A : Spectre de R.M.N. (400 MHz, (CD3)2SO d6, δ en ppm). de 1,40 à 2,35 et de 2,70 à 3,85 (mts : 29H) ; 4,01 (s : 3H) ; 5,50 (mt : 1H) ; de 5,60 à 6,40 (mf étalé : 1H) ; 7,55 (mt : 1H) ; 7,75 (d large, J = 9 Hz : 1H) ; 7,99 (d, J = 5 Hz :1H) ; 8,30 (d, J = 9 Hz : 1H) ; 9,04 (d, J = 5 Hz : 1H) ; 10,80 (mf : 1H). diastéréoisomère B : Spectre de R.M.N. ^H (400 MHz, (CD3)2SO d6, δ en ppm). de 1,35 à 2,25 et de 2,70 à 3,80 (mts : 29H) ; 4,00 (s : 3H) ; 5,49 et 5,55 (2mts : 1H entotalité) ; de 5,75 à 6,20 (mf étalé : 1H) ; 7,56 et 7,62 (2s larges : 1H en totalité) ; 7,71(d large, J = 9 Hz : 1H) ; 7,92 (mt : 1H) ; 8,24 (d, J = 9 Hz : 1H) ; 9,00 (d, J = 4 Hz :1H) ; 10,56 (mf : 1H). (3R,4R)-4-[3-(R,S)-Hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2- (cycIoheptylthio)éthyl]pipéridine-3-carboxylate de méthyle. A un mélange de 2,5 g de (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(cycloheptylthio)éthyl]pipéridine-3-carboxylate de méthyle dans 20 cm3 de méthanol,on ajoute par petites fractions à une température voisine de 20°C, sous agitation etsous atmosphère inerte, 0,221 g de borohydrure de sodium. Après addition, lemélange est agité pendant 2 heures à une température voisine de 20°C. Le mélangeréactionnel est évaporé sous pression réduite (5 kPa), puis le résidu obtenu est reprispar 50 cm3 de dichlorométhane et 30 cm3 d’une solution aqueuse saturée de chlorured’ammonium. La phase organique décantée est séchée sur sulfate de magnésium,filtrée puis concentrée sous pression réduite (5 kPa) à une température voisine de40°C. On obtient 2,5 g d’un produit que l’on purifie par chromatographie à pressionatmosphérique sur une colonne de gel de silice (granulométrie 20-45μ ; diamètre4 cm ; masse 150 g), en éluant par un mélange de dichlorométhane-méthanol'(95/5 envolumes) et en recueillant des fractions de 50 cm3. Les fractions contenant le produitrecherché sont réunies puis évaporées sous pression réduite (5 kPa) à une températurevoisine de 40°C. On obtient 1,95 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(cycloheptylthio)éthyl]pipéridine-3-carboxylatede méthyle, sous forme d’une huile visqueuse.A mixture of 1.8 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cycloheptylthio) ethyl) Methylperidine-3-carboxylate in 36 cm3 of dioxane with 2.8 cm3 of 5N aqueous sodium hydroxide is heated for 24 hours at a temperature in the region of 60 ° C. After cooling the reaction mixture to a temperature in the region of 20 ° C., and then concentration under reduced pressure (5 kPa) at a temperature in the region of 40 ° C., the residue obtained is purified by chromatography under atmospheric pressure on a column of silica gel (20 micron particle size). 45μ, diameter 4 cm, mass 180 g) eluting with a mixture of dichloromethane-methanol-ammonia 28% (40/5 / 0.5 by volume) and collecting fractions of 50 cm3. 3 batches are obtained which are evaporated under reduced pressure (5 kPa) at a temperature close to 40 ° C: batch A (0.48 g) corresponding to diastereoisomer A, batch B (0.6 g) corresponding to the diastereoisomer B; batch C (0.5 g) corresponding to a mixture of the two diastereoisomers. Lot A is purified in the following manner: after dissolving in 15 cm3 of dichloromethane and adding 10 cm3 of N hydrochloric ether, the gummy mixture obtained is evaporated under reduced pressure (5 kPa) at a temperature of 40 ° C. After taking up the residue with 40 cm 3 of acetonitrile and 2 cm 3 of 0.5 N hydrochloric acid, the solution obtained is evaporated under the same conditions as above. A white solid is obtained which is dried for 16 hours under reduced pressure (phosphorus vacuum, 5 kPa). After stirring in 100 cm3 of diethyl ether and then filtration, 0.514 g of (3 R, 4 R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1-dihydrochloride are obtained. [2- (Cycloheptylthio) ethyl] piperidine-3-carboxylic acid, diastereoisomer A (aD2 ° = -58.3 ° +/- 1.00 in 0.5% methanol), in the form of a solid white color. Batches B and C are treated in the same way. 0.650 g of (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3-dihydrochloride) dihydrochloride is obtained in particular with batch B ( cycloheptylthio) ethyl] piperidine-3-carboxylic acid, diastereoisomer B. (aD20 = + 120.4o +/- 1.7, in 0.5% methanol), as a white solid. Diastereoisomer A: Spectrum of R.M.N. (400 MHz, (CD3) 2SO d6, δ in ppm). from 1.40 to 2.35 and from 2.70 to 3.85 (mts: 29H); 4.01 (s: 3H); 5.50 (mt: 1H); from 5.60 to 6.40 (mf spread: 1H); 7.55 (mt: 1H); 7.75 (broad d, J = 9 Hz: 1H); 7.99 (d, J = 5 Hz: 1H); 8.30 (d, J = 9 Hz: 1H); 9.04 (d, J = 5 Hz: 1H); 10.80 (mf: 1H). diastereoisomer B: Spectrum of R.M.N. ^ H (400 MHz, (CD3) 2SO d6, δ in ppm). from 1.35 to 2.25 and from 2.70 to 3.80 (mts: 29H); 4.00 (s: 3H); 5.49 and 5.55 (2mts: 1H entotality); from 5.75 to 6.20 (mf spread: 1H); 7.56 and 7.62 (2s wide: 1H in total); 7.71 (broad d, J = 9 Hz: 1H); 7.92 (mt: 1H); 8.24 (d, J = 9 Hz: 1H); 9.00 (d, J = 4 Hz: 1H); 10.56 (mf: 1H). Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cycloheptylthio) ethyl] piperidine-3-carboxylate . To a mixture of 2.5 g of (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cycloheptylthio) ethyl] piperidine-3 methyl carboxylate in 20 cm3 of methanol, 0.221 g of sodium borohydride are added in small portions at a temperature in the region of 20 ° C., with stirring and under an inert atmosphere. After addition, the mixture is stirred for 2 hours at a temperature in the region of 20 ° C. The reaction mixture is evaporated under reduced pressure (5 kPa) and the residue obtained is taken up in 50 cm3 of dichloromethane and 30 cm3 of a saturated aqueous solution of ammonium chloride. The decanted organic phase is dried over magnesium sulphate, filtered and then concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 2.5 g of a product which is purified by atmospheric pressure chromatography on a column of silica gel (particle size 20-45μ, diameter 4 cm, mass 150 g) are obtained, eluting with a mixture of dichloromethane-methanol. (95/5 volumes) and collecting 50 cm3 fractions. The fractions containing the desired product are combined and then evaporated under reduced pressure (5 kPa) at a temperature of 40 ° C. 1.95 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cycloheptylthio) ethyl] are obtained. Piperidine-3-carboxylated methyl, in the form of a viscous oil.

Spectre infra rouge (CC1J : 3500-3100 cm’1 v OH alcool; 2930 cm'1 v CHaliphatiques; 2805,2772 cm'1 v CH2 N(CH2)3 ;1736 cm'1 v C=O ester ; 1242;1228 cm'1 v C-0 éther ;1034cm'‘ v C-0 alcool ; 854 cm'1 yCH quinoline 233 120 2 2 (3R,4R)-4-[3-Oxo-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(cycloheptylthio)éthyl]pipéridine-3-carboxylate de méthyleInfrared spectrum (CCl 3: 3500-3100 cm -1 alcohol, 2930 cm -1 CHaliphatics, 2805.2772 cm -1 CH 2 N (CH 2) 3, 1736 cm -1 C = O ester, 1242; C 10 -0- (C) -O- (C) -O- (C) -O- (C) -O- (C) -O- (C) -O- (C) -O- (C) -O- (C) -O- (3R, 4R) -4- [3-Oxo-3- (6-methoxyquinolin) -4- yl) methyl propyl] -1- [2- (cycloheptylthio) ethyl] piperidine-3-carboxylate

Un mélange constitué par 3,06 g de (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-carboxylate de méthyle, 1,79 g de 2-chloroéthylcycloheptylsulfure, 5,39 g de carbonate de potassium, 1,29 g d’iodure de potassium dans 75 cm3d’acétonitrile est chauffé sous agitation et sous atmosphère inerte à une températurevoisine de 72°C pendant 24 heures. Après refroidissement à environ 20°C, le mélange.réactionnel est filtré sur célite, puis le filtrat est concentré sous pression réduite(5 kPa) ’ à une température voisine de 40°C. Le résidu obtenu est purifié parchromatographie à pression atmosphérique sur une colonne de gel de silice(granulométrie 20-45μ ; diamètre 4 cm ; masse 150 g), en éluant par un mélangeacétate d’éthyle-méthanol (95/5 en volumes) et en recueillant des fractions de 50 cm3.Les fractions contenant le produit recherché sont réunies puis concentrées souspression réduite (5 kPa) à une température voisine de 40°C. On obtient 2,6 g de(3R,4R)-4-[3-oxo-3 -(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(cycloheptylthio)éthyI]pipéridine-3-carboxylate de méthyle, sous forme d’une huile visqueuse.A mixture consisting of 3.06 g of methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate, 1.79 g of 2- chloroethylcycloheptylsulphide, 5.39 g of potassium carbonate, 1.29 g of potassium iodide in 75 cm3 of acetonitrile is heated with stirring and under an inert atmosphere at a temperature of 72 ° C for 24 hours. After cooling to about 20 ° C., the reaction mixture is filtered on celite and the filtrate is concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. The residue obtained is purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45μ, diameter 4 cm, mass 150 g), eluting with a mixture of ethyl acetate-methanol (95/5 by volume) and with collecting fractions of 50 cm3. The fractions containing the desired product are combined and then concentrated under reduced pressure (5 kPa) at a temperature of 40 ° C. 2.6 g of (3R, 4R) -4- [3-oxo-3 - (6-methoxyquinolin-4-yl) propyl] -1- [2- (cycloheptylthio) ethyl] piperidine-3-carboxylate are obtained. methyl, in the form of a viscous oil.

Spectre infra rouge (CC1„) : 2930 cm'1 v CH aliphatiques ;2805,2767 cm'1 v CH2N(CH2)3 ; 1740 cm'* v C=O ester ; 1693 cm'1 v C=O cétone ; 1241,1228 cm'1 v C-0éther ; 850 cm'1 yCH quinoline 2-ChIoroéihyl.ycioheptyl sulfure A une solution de 1,74 g de 2-hydroxyéthylcyeIohepfylsuliure dans 30 cm3 dechloroforme, on ajoute goutte à goutte sous agitation et sous atmosphère inerte5,11 cm3 de chlorure de thionyle à une température voisine de 20°C. Après l’additionle mélange réactionnel est agité d’abord pendant 15 minutes à cette mêmetempérature, puis pendant 1 heure à une température voisine de 60°C. Le mélange estévaporé à sec sous pression réduite (5 kPa) à une température voisine de 40°C, puis lerésidu obtenu est repris par 2 fois 50 cm3 d’eau puis 1 fois par 50 cm3 d’une solutionsaturée d’hydrogénocarbonate de sodium. La solution éthérée décantée est séchée sursulfate de magnésium, filtrée puis concentrée sous pression réduite (5 kPa) à unetempérature voisine de 40°C. On obtient 1,89 g de 2-chloroéthylcycloheptyl sulfuresous forme d’huile.Infrared spectrum (CCl 2): 2930 cm -1 CH 2 aliphatic; 2805.2767 cm -1 CH 2 N (CH 2) 3; 1740 cm -1 C = O ester; 1693 cm -1 C = O ketone; 1241.1228 cm -1 C 0 ether; 850 cm -1 CH 2-quinoline-2-chloro-1-yloxyheptyl sulfide To a solution of 1.74 g of 2-hydroxyethylcyclohexylpulphide in 30 cm3 of chloroform was added dropwise with stirring and under an inert atmosphere 5.11 cc of thionyl chloride at room temperature. close to 20 ° C. After the addition, the reaction mixture is stirred first for 15 minutes at this temperature, then for 1 hour at a temperature in the region of 60.degree. The mixture is evaporated to dryness under reduced pressure (5 kPa) at a temperature in the region of 40 ° C., and then the residue obtained is taken up twice with 50 cm 3 of water and then once with 50 cm 3 of a sodium hydrogen carbonate solution. The decanted ether solution is dried over magnesium sulphate, filtered and then concentrated under reduced pressure (5 kPa) at a temperature of 40 ° C. 1.89 g of 2-chloroethylcycloheptyl sulphides are obtained in the form of an oil.

Spectre infra rouge (CC14) 2930,2855 cm'1 v CH2; 1459,1445 cm'1 δ CH2 ;1210 cm'1ω C-Cl ; 702 cm'1 v C-Cl 120 2 2 234 2-HydroxyéthylcycloheptyI sulfure A une suspension agitée de 0,91 g d’hydrure de sodium à 60 % dans 10 cm3 dediméthylformamide anhydre on ajoute lentement, sous atmosphère inerte et à unetempérature voisine de 20°C, 2,32 g de 2-mercaptoéthanol préalablement solubilisésdans 10 cm3 de diméthylformamide. Après 20 minutes d’agitation, on ajoute 3,5 g debromocycloheptane dissous dans 10 cm3 de diméthylformamide. La réaction estachevée par agitation à une température voisine de 20°C pendant 1 heure 30 minutes.Le mélange réactionnel est versé sur 150 cm3 d’eau additionnés de 100 cm3 d’étherdiéthylique. La phase éthérée est décantée, la phase aqueuse extraite une fois par50 cm3 d’éther diéthylique. Les phases organiques sont réunies puis lavées par 2 fois100 cm3 d’eau, séchées sur sulfate de magnésium, filtrées, concentrées sous pressionréduite (5 kPa) à une température voisine de 40°C. On obtient 3,2 g de 2-hydroxyéthylcycloheptyl sulfure, sous forme d’huile de couleur jaune.Infra red spectrum (CCl 2) 2930.2855 cm -1 CH 2; 1459.1451 cm -1 CH 2, 1210 cm -1 C-Cl; 702 cm -1 C-Cl 120 2 2 234 2-Hydroxyethylcycloheptyl sulfide To a stirred suspension of 0.91 g of 60% sodium hydride in 10 cm3 of anhydrous dimethylformamide is slowly added, under an inert atmosphere and at a temperature close to 20 ° C, 2.32 g of 2-mercaptoethanol previously solubilized in 10 cm3 of dimethylformamide. After stirring for 20 minutes, 3.5 g of bromocycloheptane dissolved in 10 cm3 of dimethylformamide are added. The reaction is completed by stirring at a temperature in the region of 20 ° C. for 1 hour 30 minutes. The reaction mixture is poured into 150 cm 3 of water added with 100 cm 3 of diethyl ether. The ether phase is decanted, the aqueous phase extracted once with 50 cm3 of diethyl ether. The organic phases are combined and then washed with 2 times 100 cm3 of water, dried over magnesium sulphate, filtered and concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 3.2 g of 2-hydroxyethylcycloheptyl sulphide are obtained in the form of a yellow oil.

Spectre infra rouge (CH2C12) 3608,3457 cm'1 v OH (libre et lié) ;2927,2855 cm'1 v CHaliphatiques ;1057 cm'1 v COInfrared spectrum (CH 2 Cl 2) 3608.3457 cm -1 OH (free and bound) 2927.2855 cm -1 CH aliphatics 1057 cm -1 CO

Exemple 41Example 41

Dichlorhydrate de l’acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yI)propyl]-l-[2-(2-thiénylthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-acetic acid dihydrochloride

Un mélange agité de 0,598 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2-thiénylthio)éthyl]pipéridine-3-acétate de méthyle dans 13 cm3 de dioxanne avec1 cm3 de soude aqueuse 5N, en atmosphère inerte, est chauffé à 60°C pendant 20heures. Après évaporation du mélange réactionnel sous pression réduite (5 kPa) à unetempérature voisine de 50°C, on obtient 1 g d’une meringue jaune que l’on purifie parchromatographie à pression atmosphérique sur une colonne de gel de silice(granulométrie 20-45μ ; diamètre 3 cm; hauteur silice 21 cm) en éluant par unmélange chloroforme-méthanol-ammoniaque à 28% (12/3/0,5 en volumes) et enrecueillant des fractions de 50 cm3. Les fractions 4 à 7 sont réunies puis évaporéessous pression réduite (5 kPa) à une température voisine de 40°C. On obtient 0,495 gd’un produit que l’on dissout dans 5 cm3 de dichlorométhane. Après addition de10 cm3 d’éther chlorhydrique IN, on obtient un précipité pâteux que l’on dilue parÎ00 cm3 d’éther diéthylique. Le mélange est agité à une température voisine de 20°C.La suspension blanche obtenue est filtrée, lavée par 3 fois 30 cm3 d’éther diéthylique.Le solide blanc résultant est séché sous pression réduite (10 Pa) à une température 235 120 2 2 voisine de 40°C jusqu'à obtention d’un poids constant. On obtient 0,55 g dedichlorhydrate de l’acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2-thiénylthio)éthyl]pipéridine-3-acétique, sous forme d’un solide blanc fondant en seramollissant au voisinage de 200°C.A stirred mixture of 0.598 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-methyl acetate in 13 cm3 of dioxane with 1 cm3 of 5N aqueous sodium hydroxide, in an inert atmosphere, is heated at 60 ° C for 20 hours. After evaporation of the reaction mixture under reduced pressure (5 kPa) at a temperature in the region of 50 ° C., 1 g of a yellow meringue is obtained which is purified by atmospheric pressure chromatography on a column of silica gel (particle size 20-45μ diameter 3 cm, silica height 21 cm) eluting with a chloroform-methanol-ammonia mixture at 28% (12/3 / 0.5 by volume) and containing fractions of 50 cm 3. Fractions 4 to 7 are combined and then evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 0.495 g of a product is obtained which is dissolved in 5 cm3 of dichloromethane. After addition of 10 cm3 of 1N hydrochloric ether, a pasty precipitate is obtained which is diluted with 100 cm3 of diethyl ether. The mixture is stirred at a temperature in the region of 20 ° C. The white suspension obtained is filtered and washed with diethyl ether (3 × 30 cc). The resulting white solid is dried under reduced pressure (10 Pa) at a temperature of 235 ° C. 2 about 40 ° C until a constant weight. 0.55 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-dihydrochloride is obtained acetic acid, in the form of a white solid melting in the vicinity of 200 ° C.

Spectre de R.M.N. (400 MHz, (CD3)2SO d6 à une température de 383K, δ enppm) : de 1,40 à 1,95 (mt : 8H) ; 2,30 (dd, J = 16 et 5,5 Hz : 1H) ; de 2,45 à 2,60 (mt :1H) ; de 3,00 à 3,35 (mt : 10H) ; 4,00 (s : 3H) ; 7,08 (dd, J = 5 et 3,5 Hz : 1H) ; 7,28(d large, J = 3,5 Hz : 1H) ; de 7,45 à 7,55 (mt : 2H) ; 7,56 (dd, J = 9,5 et 3 Hz : 1 H) ;7,62 (d large, J = 5 Hz : 1H) ; 8,15 (d, J = 9,5 Hz : 1H) ; 8,75 (d, J = 5 Hz : 1H).Spectrum of R.M.N. (400 MHz, (CD3) 2SO d6 at a temperature of 383K, δ enppm): from 1.40 to 1.95 (mt: 8H); 2.30 (dd, J = 16 and 5.5 Hz: 1H); from 2.45 to 2.60 (mt: 1H); from 3.00 to 3.35 (mt: 10H); 4.00 (s: 3H); 7.08 (dd, J = 5 and 3.5 Hz: 1H); 7.28 (broad d, J = 3.5 Hz: 1H); from 7.45 to 7.55 (mt: 2H); 7.56 (dd, J = 9.5 and 3 Hz: 1H), 7.62 (broad d, J = 5 Hz: 1H); 8.15 (d, J = 9.5 Hz: 1H); 8.75 (d, J = 5 Hz: 1H).

Exemple 41A (3R,4R)-4-[3-(6-Méthoxyquinolin-4-yl)propyl]-l-[2-(2- thiényithio)éthyl}pipérïdine-3-acétate de méthyle A une solution agitée de 2,1 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4--yI)propyl]pipéridine-3-acétate de méthyle et de 1,15 g de 2-(2-chloroéthylthio) thiophène dans50 cm3 d’acétonitrile, on ajoute sous atmosphère inerte 4,06 g de carbonate depotassium puis 1 g d’iodure de potassium. Le mélange est chauffé à 70°C pendant 20heures. Après refroidissement à une température voisine de 20°C, le mélangeréactionnel est dilué par 100 cm3 d’acétate d’éthyle et 100 cm3 d’eau. Après agitationdu mélange et décantation de la phase organique, la phase aqueuse est extraite par 2fois 50-cm3 d’acétate d’éthvle. Les phases organiques sont réunies, extraites par 3 fois50 cm3 d’acide chlorhydrique aqueux N. Les solutions acides sont réunies, amenées àpH 8 par la quantité suffisante d’hydrogénocarbonate de sodium. L’huile relarguéerésultante est extraite par 3 fois 100 cm3 d’acétate d’éthyle. Les extraits réunis sontséchés sur sulfate de magnésium, filtrés, évaporés sous pression réduite (5 kPa) à unetempérature voisine de 40°C. On obtient 1,5 g d’une huile de couleur orangée quel’on purifie par chromatographie à pression atmosphérique sur une colonne de gel desilice (granulométrie 20-45μ ; diamètre 3 cm ; hauteur silice 55 cm) en éluant par del’acétate d’éthyle pur et en recueillant des fractions de 50 cm3. Les fractions 12 à 30sont réunies puis évaporées dans les mêmes conditions que ci-dessus. On obtient0,60 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyI]-l-[2-(2-thiénylthio)éthyl]pipéridine-3-acétate de méthyle, sous forme d’une huile visqueuse incolore. 236 120 2 2Example 41A (3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [2- (2-thienyl) thio] ethyl] piperidin-3-methyl acetate To a stirred solution of 2 1 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate and 1.15 g of 2- (2-chloroethylthio) thiophene in 50 g. cm.sup.3 of acetonitrile, 4.06 g of potassium carbonate and 1 g of potassium iodide are added under an inert atmosphere. The mixture is heated at 70 ° C for 20 hours. After cooling to a temperature of 20 ° C, the reaction mixture is diluted with 100 cm3 of ethyl acetate and 100 cm3 of water. After stirring the mixture and decanting the organic phase, the aqueous phase is extracted twice with 50 ml of ethyl acetate. The organic phases are combined, extracted with 3 times 50 cm3 of aqueous hydrochloric acid N. The acid solutions are combined, brought to pH 8 by the sufficient amount of sodium hydrogencarbonate. The resulting oil is extracted with 3 times 100 cm3 of ethyl acetate. The combined extracts are dried over magnesium sulphate, filtered and evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 1.5 g of an orange-colored oil are obtained, which is purified by chromatography at atmospheric pressure on a desilicose gel column (particle size 20-45 μ, diameter 3 cm, silica height 55 cm), eluting with sodium acetate. pure ethyl and collecting 50 cm3 fractions. Fractions 12 to 30 are combined and then evaporated under the same conditions as above. 0.60 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-acetate are obtained. form of a viscous colorless oil. 236 120 2 2

Spectre infra rouge (CHjCy 2933,2861 cm'1 v CH aliphatiques ;2803,2766 cm'1 vCH2 N(CH2)3;173l cm'1 v C=O ester ;1242,1227cnï' v C-0 éther; 847 cm'1 yCHquinolineIR spectrum (CH 2 Cl 2) 2933.2861 cm -1 CH 2 aliphatic; 2803.2766 cm -1 CH 2 N (CH 2) 3; 173l cm -1 C = O ester; 1242.12 g / cm 2 C 0 ether; 847 cm -1 '1 yCHquinoline

Le (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-acétate de méthyle a5 été préparé selon le mode opératoire décrit dans l’exemple 36.Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate was prepared according to the procedure described in Example 36.

Exemple 43Example 43

Acide (3R,4R)-4-[3-hydroxy-3-(6-méthoxyquînolin-4-yl)propyl]-l-[2- (cyclohexylthio)éthyI]pipéridine-3-carboxylique, diastéréoisomère A et acide(3R,4R)-4-[3-hydroxy-3-(6-méthoxyquinoIin-4-yI)propyI]-l-[2- 10 (cycIohexylthio)éthyl]pipéridine-3-carboxylique, diastéréoisomère B. 5 g d’acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyI]-l-[2-(cycIohexylthio)éthyl]pipéridine-3-carboxylique dissous dans 100 cm3 d’un mélangede dichlorométhane-éthanol-tétrahydrofuranne (65/15/20 en volumes) sontchromatographiés sur une colonne de 35 cm de long et 8 cm de diamètre, 15 conditionnée avec 1,200 kg de silice KROMASIL® (granulométrie 10 μ). L’élutionest effectuée à l’aide du même mélange que ci-dessus. Le débit est de 150 cm3 parminute pendant les 30 premières minutes, puis 200 cm3 par minute au-delà. Ladétection est effectuée en ultra violet 280 nm. Cette opération conduit à l’obtentiondes deux diastéréoisomères. Les fractions correspondantes au premier sont 20 concentrées à sec sous pression réduite (5 kPa) à une température voisine de 40°C. Onobtient un résidu solide que l’on reprend dans l’éther diéthylique, filtre, sèche à l’air àune température voisine de 20°C. On obtient 1,5 g d’acide (3R,4R)-4-[3-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(cyclohexylthio)éthyl]pipéridine-3-carboxylique, diastéréoisomère A. (ccD20 =-47,1° +/-0,9 dans le dichlorométhane à 25 0,5 %), sous forme d’un solide de couleur beige. Les fractions correspondant au second diastéréoisomère sont traitées comme précédemment. On obtient 1,7 g d’acide(3R,4R)-4-[3-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(cyclohexylthio)éthyl]pipéridine-3-carboxylique, diastéréoisomère B. (¾20 =+98,7° +/-1,6 dans ledichlorométhane à 0,5 %). sous forme d’un solide de couleur beige. 30 diastéréoisomère A : Spectre de R.M.N. (300 MHz, (CD3)2SO d6, δ en ppm) : de 1,10 à 2,05 (mts : 17H) ; 2,33 (t très large, J = 10 Hz : 1H) ; 2,45 (d large, J = 10 Hz :1H) ; 2,59 (mf : 1H) ; de 2,60 à 2,80 (mt : 5H) ; 2,90 (d large, J = 10 Hz : 1H) ; 3,06(d large, J = 10 Hz : 1H) ; 3,96 (s : 3H) ; 5,22 (d très large, J = 7 Hz : 1H) ; de 5,40 à 120 22 237 5,70 (mf étalé : 1H) ; de 7,30 à 7,45 (mt : 2H) ; 7,57 (d, J = 4,5 Hz : 1H) ; 7,94 (d, J =9 Hz : 1H) ; 8,72 (d, J = 4,5 Hz : 1H) ; de 12,50 à 13,40 (mf très étalé : 1H). diastéréoisomère B : Spectre de R.M.N. ^H (300 MHz, (CD3)2SO d6, δ en ppm) : de 1,10 à 2,00 (mts : 17H) ; 2,33 (mt : 1H) ; de 2,40 à 2,55 (mt : 1H) ; 2,57 (s large :1H) ; de 2,60 à 2,80 (mt : 5H) ; 2,82 (mt : 1H) ; 2,99 (mt : 1H) ; 3,92 (s : 3H) ; 5,25(mt : 1H) ; de 5,40 à 5,70 (mf étalé : 1H) ; de 7,35 à 7,45 (mt : 2H) ; 7,53 (d, J = 4,5Hz : 1H) ; 7,94 (d, J = 10 Hz : 1H) ; 8,71 (d, J = 4,5 Hz : 1H) ; de 12,40 à 13,50 (mftrès étalé : 1H). L’acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]rl-[2-(cyclo-hexylthio)éthyl]pipéridine-3-carboxylique a été préparé à partir de son chlorhydrateselon le procédé suivant.(3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperidine-3-carboxylic acid, diastereoisomeric acid and acid (3R) , 4R) -4- [3-hydroxy-3- (6-methoxyquinin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperidine-3-carboxylic acid, diastereoisomer B. 5 g of acid (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperidine-3-carboxylic acid dissolved in 100 cm3 of a mixture of dichloromethane-ethanol-tetrahydrofuran (65/15/20 by volume) are chromatographed on a column 35 cm long and 8 cm in diameter, conditioned with 1,200 kg of silica KROMASIL® (particle size 10 μ). The elution is carried out using the same mixture as above. The flow rate is 150 cm3 per minute during the first 30 minutes, then 200 cm3 per minute beyond. The detection is carried out in ultraviolet 280 nm. This operation leads to obtaining the two diastereoisomers. The fractions corresponding to the first are concentrated to dryness under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. A solid residue is obtained which is taken up in diethyl ether, filtered and dried in air at a temperature of 20 ° C. 1.5 g of (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperidine-3- acid are obtained. carboxylic acid, diastereoisomer A. (ccD20 = -47.1 ° +/- 0.9 in 0.5% dichloromethane), as a beige solid. The fractions corresponding to the second diastereoisomer are treated as previously. 1.7 g of (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperidine-3- acid are obtained. carboxylic acid, diastereoisomer B. (¾20 = + 98.7 ° +/- 1.6 in 0.5% dichloromethane). in the form of a beige solid. Diastereoisomer A: NMR Spectrum (300 MHz, (CD3) 2SO d6, δ in ppm): from 1.10 to 2.05 (mts: 17H); 2.33 (very broad t, J = 10 Hz: 1H); 2.45 (broad d, J = 10 Hz: 1H); 2.59 (mf: 1H); from 2.60 to 2.80 (mt: 5H); 2.90 (broad d, J = 10 Hz: 1H); 3.06 (broad d, J = 10 Hz: 1H); 3.96 (s: 3H); 5.22 (very broad d, J = 7 Hz: 1H); from 5.40 to 120 22 237 5.70 (mf spread: 1H); from 7.30 to 7.45 (mt: 2H); 7.57 (d, J = 4.5 Hz: 1H); 7.94 (d, J = 9 Hz: 1H); 8.72 (d, J = 4.5 Hz: 1H); from 12.50 to 13.40 (mf very spread: 1H). diastereoisomer B: Spectrum of R.M.N. H (300 MHz, (CD3) 2SO d6, δ in ppm): from 1.10 to 2.00 (mts: 17H); 2.33 (mt: 1H); from 2.40 to 2.55 (mt: 1H); 2.57 (brs: 1H); from 2.60 to 2.80 (mt: 5H); 2.82 (mt: 1H); 2.99 (mt: 1H); 3.92 (s: 3H); 5.25 (mt: 1H); from 5.40 to 5.70 (mf spread: 1H); from 7.35 to 7.45 (mt: 2H); 7.53 (d, J = 4.5Hz: 1H); 7.94 (d, J = 10 Hz: 1H); 8.71 (d, J = 4.5 Hz: 1H); from 12.40 to 13.50 (spread over 1H). (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperidine-3-acid Carboxylic acid was prepared from its hydrochloride by the following method.

Dichlorhydrate de l’acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yI)propyl]-l-[2-(cyclohexylthio)éthyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] piperidine hydrochloride dihydrochloride 3-carboxylic acid

On chauffe 0,4 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyî]-l-[2-(cyclohexylthio)éthyI]pipéridine-3-carboxylate de méthyle dans 3 cm3 deméthanol additionnés de 0,48 cm3 de soude aqueuse 5N en atmosphère inerte pendant16 heures. Après concentration de la masse réactionnelle sous pression réduite (5 kPa)à une température voisine de 40°C, on reprend le résidu obtenu dans 5 cm3 d’acidecl do· -hydrique 6N, puis 2,5 cm3 c-e .néthanol. La solution brune obtenue est évaporéedans les mêmes conditions que c’-dcc-.iis. Le rcsidu qui en résulte est repris dans 5cm3 d’étl.'cr diisopropylique, filtré, lavé, par 2 fois 3 cm3 du même solvant. Le solideobtenu est séché sous pression réduite (13 Pa) à une température voisine de 60°C. Onobtient 0,37 g de dichlorhydrate de l’acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(cycIohexylthio)éthyl]pipéridine-3-carboxylique,sous forme d’un solide de couleur brune fondant en se ramollissant au voisinage de170°C.0.4 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] are heated methyl piperidine-3-carboxylate in 3 cm3 of ethanol added with 0.48 cm3 of 5N aqueous sodium hydroxide in an inert atmosphere for 16 hours. After concentrating the reaction mass under reduced pressure (5 kPa) at a temperature in the region of 40 ° C., the residue obtained is taken up in 5 cm3 of 6N hydrochloric acid and then 2.5 cm3 of ethanol. The brown solution obtained is evaporated under the same conditions as that obtained. The resulting residue is taken up in 5 cm 3 of diisopropyl ether, filtered, washed, twice with 3 cm 3 of the same solvent. The solidobtained is dried under reduced pressure (13 Pa) at a temperature in the region of 60.degree. 0.37 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3 - ((R)) dihydrochloride salt are obtained. (cyclohexylthio) ethyl] piperidine-3-carboxylic acid as a brown solid melting at about 170 ° C.

Spectre de RM.N.^H (400 MHz, (CD3)2SO d6, à une température de 383K, δ enppm). On observe un mélange de deux diastéréoisomères : de 1,20 à 2,25 et de 2,80 à 3,40 (mts : 25H) ; 3,28 (t, J = 8 Hz : 2H) ; 4,00 (s : 3H) ; 5,36 (mt : 1H) ; de 7,50 à 7,65 (mt : 2H) ; 7,70 (mt : 1 H) ; 8,13 (d large, J = 9 Hz :1H) ; 8,81 (d, J = 5 Hz: 1H). 120 2 2 238 (3R,4R)-4-(3-(R,S)-Hydroxy-3-(6-méthoxyquinoIin-4-yI)propyIJ-l-[2-(cycIohexyIthio)éthyI]pipéridine-3-carboxylate de méthyle1 H NMR spectrum (400 MHz, (CD3) 2SO d6, at a temperature of 383K, δppm). There is a mixture of two diastereoisomers: from 1.20 to 2.25 and from 2.80 to 3.40 (mts: 25H); 3.28 (t, J = 8 Hz: 2H); 4.00 (s: 3H); 5.36 (mt: 1H); from 7.50 to 7.65 (mt: 2H); 7.70 (mt: 1H); 8.13 (broad d, J = 9 Hz: 1H); 8.81 (d, J = 5 Hz: 1H). 2,228 (3R, 4R) -4- (3- (R, S) -Hydroxy-3- (6-methoxyquinin-4-yl) propyl] -1- (2- (cyclohexylthio) ethyl] piperidine-3 methyl carboxylate

Un mélange agité de 0,54 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-carboxyIate de méthyle, 0,295 g de 2-chloroéthylcyclohexylsulfure, 0,23 g de carbonate de potassium, 0,27 g d’iodure de potassium dans 9 cm3d’acétonitrile et 1 cm3 de méthanol est porté à une température voisine de l’ébullitionsous atmosphère inerte pendant 20 heures. Le mélange réactionnel est concentré souspression réduite (5 kPa) à une température voisine de 40°C. Le résidu obtenu estpurifié par chromatographie sous une pression d’argon de 80 kPa, sur une colonne degel de silice (granulométrie 40-63μ ; diamètre 3,5 cm ; hauteur 35 cm) en éluant parun mélange de dichlorométhane-méthanol (95/5 en volumes), et en recueillant desfractions de 35 cm3. Les fractions 23 à 40 sont réunies puis concentrées sous pressionréduite (5 kPa) à une température voisine de 40°C. On obtient 0,4 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(cycIohexyJthio)éthyl]pipéridine-3-carboxylate de méthyle, sous forme d’une laque de couleur brune.A stirred mixture of methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate, 0.54 g, 0.295 g. 2-chloroethylcyclohexylsulfide, 0.23 g of potassium carbonate, 0.27 g of potassium iodide in 9 cm3 of acetonitrile and 1 cm3 of methanol are brought to a temperature close to boiling under an inert atmosphere for 20 hours. The reaction mixture is concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. The residue obtained is purified by chromatography under an argon pressure of 80 kPa, on a silica gel column (particle size 40-63μ, diameter 3.5 cm, height 35 cm), eluting with a mixture of dichloromethane-methanol (95/5 in volumes), and collecting 35 cc fractions. Fractions 23 to 40 are combined and then concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 0.4 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylthio) ethyl] are obtained. methyl piperidine-3-carboxylate, in the form of a brown lacquer.

Spectre infra rouge (CC14) 3600-3200 cm'1 vOH; 2932,2854 cm"1 vCH aliphatiques;1736 cm'1 v C=O ; 1242 cm'1 v C-0 étherInfrared spectrum (CCl 4) 3600-3200 cm -1 vOH; 2932.2854 cm -1 aliphatic vCH 1736 cm -1 C = O 1242 cm -1 C 0 ether

Exemple 44Example 44

Acide (3R,4R)-4-[3-hydroxy-3-(6-méthoxyquinolin-4-yI)propyl]-l-[3-(thién-2-yl)prop-2-ynyI]pipéridine-3-carboxylique, diastéréoisomère A et acide (3R,4R)- 4-[3-hydroxy-3-(6-méthoxyquinoIin-4-yl)propyl]-l-[3-(thién-2-yl)prop-2-ynyI]pipéridine-3-carboxylique, diastéréoisomère B. 3 g d’acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thién-2-yl)prop-2-ynyl]pipéridine-3-carboxylique dissous dans 100 cm3 d’unmélange de dichlorométhane-méthanol-acétonitrile (85/8/7 en volumes) sontchromatographiés sur une colonne de 35 cm de long et 8 cm de diamètre,conditionnée avec 1,200 kg de silice KROMASIL® (granulométrie lOu). L’élution esteffectuée à l’aide du même mélange que ci-dessus. La détection est effectuée en ultraviolet à 280 nm. Cette opération conduit à l’obtention des deux diastéréoisomères.Les fractions correspondant au premier sont concentrées à sec sous pression réduite (5kPa) à une température voisine de 40°C. On obtient un résidu solide que l’on sèchesous pression réduite (23 Pa) à une température voisine de 20°C. On obtient 0,612 gd’acide (3R,4R)-4-[3-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thién-2- 120 2 2 239 yl)prop-2-ynyl]pipéridine-3-carboxylique carboxylique, diastéréoisomère A. (aD20 =-67,5° +/-1,3 dans Je dichlorométhane à 0,5%), sous forme d’une meringue de couleurblanche. Les fractions correspondant au second diastéréoisomère sont traitées commeprécédemment. On obtient 0,596 g d’acide (3R,4R)-4-[3-hydroxy-3-(6-méthoxyquinoIin-4-yl)propyl]-l-[3-(thién-2-yl)prop-2-ynyl]pipéridine-3-carboxylique, diastéréoisomère B. (aD20 =+106,0° +/-1,6 dans le dichlorométhane à0,5 %), sous forme d’une meringue de couleur blanche. diastéréoisomère A : Spectre de R.M.N. (300 MHz, (CD3)2SO d6, δ en ppm) : de 1.40 à 1,95 (mt : 7H) ; 2,40 (mt : 1H) ; de 2,50 à 2,60 (mt : 1 H) ; de 2,60 à 280 (mt :2H) ; 2,90 (mf : 1H) ; 3,63 (s : 2H) ; 3,94 (s : 3H) ; 5,24 (mt : 1H) ; 5,52 (mt : 1H) ;7,08 (dd, J = 5 et 4 Hz : 1H); 7,31 (dd, J = 4 et 1 Hz : 1H) ; 7,35 (d, J = 3 Hz : 1H) ; 7.40 (dd, J = 9 et 3 Hz : 1H) ; 7,56 (d, J = 4,5 Hz : 1H) ; 7,59 (dd, J = 5 et 1 Hz : 1H) ;7,95 (d, J = 9 Hz : 1H) ; 8,71 (d, J = 4,5 Hz : 1H). diastéréoisomère B : Spectre de R.M.N. (300 MHz, (CD3)2SO d6, δ en ppm) : de1,20 à 1,95 (mt : 7H) ; 2,38 (mt : 1H) ; de 2,50 à 2,75 (mt : 3H) ; 2,71 (mf : IH) ; 3,58(s : 2H) ; 3,90 (s : 3H) ; 5,25 (mt : 1H) ; 5,52 (mt : 1H) ; 7,07 (dd, J = 5 et 3,5 Hz :1H) ; 7,29 (d large, J = 3,5 Hz : 1H) ; de 7,30 à 7,45 (mt : 2H) ; 7,53 (d, J = 4,5 Hz :1H) ; 7,58 (d large, J = 5 Hz : 1H) ; 7,94 (d, J = 10 Hz : 1H) ; 8,70 (d, J = 4,5 Hz :1H).(3R, 4R) -4- [3-Hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-yl] propyl] piperidine-3- acid Carboxylic acid, diastereoisomer A and (3R, 4R) - 4- [3-hydroxy-3- (6-methoxyquinin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-yn] ] piperidine-3-carboxylic acid, diastereoisomer B. 3 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-3-carboxylic acid dissolved in 100 cm3 of a mixture of dichloromethane-methanol-acetonitrile (85/8/7 by volume) are chromatographed on a 35 cm column long and 8 cm in diameter, conditioned with 1,200 kg of KROMASIL® silica (particle size lOu). The elution is carried out using the same mixture as above. The detection is carried out in ultraviolet at 280 nm. This operation leads to obtaining the two diastereoisomers. The fractions corresponding to the first are concentrated to dryness under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. A solid residue is obtained which is dried under reduced pressure (23 Pa) at a temperature in the region of 20 ° C. 0.612 g of (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) propyl) propane is obtained. 2-ynyl] piperidine-3-carboxylic carboxylic acid, diastereoisomer A. (aD20 = -67.5 ° +/- 1.3 in 0.5% dichloromethane), as a white meringue. The fractions corresponding to the second diastereoisomer are treated as before. 0.596 g of (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-yl) acid is obtained. ynyl] piperidine-3-carboxylic acid, diastereoisomer B. (aD20 = + 106.0 ° +/- 1.6 in 0.5% dichloromethane), in the form of a white meringue. diastereoisomer A: Spectrum of R.M.N. (300 MHz, (CD3) 2SO d6, δ in ppm): from 1.40 to 1.95 (mt: 7H); 2.40 (mt: 1H); from 2.50 to 2.60 (mt: 1H); from 2.60 to 280 (mt: 2H); 2.90 (mf: 1H); 3.63 (s: 2H); 3.94 (s: 3H); 5.24 (mt: 1H); 5.52 (mt: 1H), 7.08 (dd, J = 5 and 4 Hz: 1H); 7.31 (dd, J = 4 and 1 Hz: 1H); 7.35 (d, J = 3 Hz: 1H); 7.40 (dd, J = 9 and 3 Hz: 1H); 7.56 (d, J = 4.5 Hz: 1H); 7.59 (dd, J = 5 and 1 Hz: 1H), 7.95 (d, J = 9 Hz: 1H); 8.71 (d, J = 4.5 Hz: 1H). diastereoisomer B: Spectrum of R.M.N. (300 MHz, (CD3) 2SO d6, δ in ppm): from 1.20 to 1.95 (mt: 7H); 2.38 (mt: 1H); from 2.50 to 2.75 (mt: 3H); 2.71 (mf: 1H); 3.58 (s: 2H); 3.90 (s: 3H); 5.25 (mt: 1H); 5.52 (mt: 1H); 7.07 (dd, J = 5 and 3.5 Hz: 1H); 7.29 (broad d, J = 3.5 Hz: 1H); from 7.30 to 7.45 (mt: 2H); 7.53 (d, J = 4.5 Hz: 1H); 7.58 (broad d, J = 5 Hz: 1H); 7.94 (d, J = 10 Hz: 1H); 8.70 (d, J = 4.5 Hz: 1H).

Exci.tplc -',5Exci.tplc - ', 5

Acide (3R/R}-4~[3-(R,S)-hydroxy-3~(6--t;R.tIiyxyquinoIhi-4-yI)prupyI]-l-[2-(5-chlorothién-2-yi)]pipéridine-3-earboxyîique(3R / R) -4- [3- (R, S) -hydroxy-3 ~ (6-t; R) -I-hydroxyquinyl-4-yl) -propyl] -1- [2- (5-chlorothien-2) -acid -yi)] piperidin-3-earboxyîique

Une solution de 0,460 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyI]-l-[2-(5-chIorothién-2-yI)]pipéridine-3-carboxylate de méthyle dans 5 cm3 dedioxanne additionnés de 0,51 cm3 d’une solution aqueuse de soude 5N est agitée àune température voisine de 60°C pendant 48 heures. Après une additionsupplémentaire de 1 cm3 de soude 5N, le mélange est de nouveau chauffé à unetempérature voisine de 70°C pendant 72 heures. Le mélange réactionnel est évaporésous pression réduite (5 kPa) à une température voisine de 45°C, puis le résidu obtenuest purifié par chromatographie sous une pression d’azote de 40 kPa, sur une colonnede gel de silice (granulométrie 40-63μ ; diamètre 3 cm ; hauteur de silice 27 cm), enéluant par un mélange de dichlorométhane-méthanol-ammoniaque à 28% (14/4/0,6 envolumes) et en recueillant des fractions de 15 cm3. Les fractions 7 à 16 sont évaporées 120 2 2 240 sous pression réduite (5 kPa) à une température voisine de 40°C. On obtient 0,30 g d’acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propylj-1 -f2-(5- chlorothién-2-yl)]pipéridine-3-carboxylique, sous forme d’une meringue de couleurblanche. 5 Spectre de R.M.N. ’H (300 MHz, (CD3)2SO d6, δ en ppm). On observe un mélange dedeux diastéréoisomères : de 1,40 à 3,10 (mts : 16H) ; 3,92 et 3,95 (2 s : 3H en totalité) ; 5,23 (mt : 1H) ; 5,50(mt : 1H) ; de 7,05 à 7,15 (mt : 2H) ; de 7,30 à 7,45 (mt : 2H) ; 7,52 et 7,54 (2 d, J = 5Hz : 1H en totalité) ; 7,94 (mt : 1H) ; 8,70 (d, J = 5 Hz : 1H). 10 (3R,4R)-4-[3-(R,S)-Hydroxy-3-(6-méthoxyquinoIin-4-yl)propyl]-l-[2-(5-chIorothién-2-yI)]pipéridine-3-carboxyIate de méthyleA solution of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (5-chlorothien-2), 0.460 g. -yi)] piperidine-3-carboxylic acid methyl ester in 5 cm3 of dedioxane supplemented with 0.51 cm3 of a 5N aqueous sodium hydroxide solution is stirred at a temperature of 60 ° C for 48 hours. After an additional addition of 1 cm3 of 5N sodium hydroxide, the mixture is again heated to a temperature of 70 ° C for 72 hours. The reaction mixture is evaporated under reduced pressure (5 kPa) at a temperature in the region of 45 ° C., and the residue obtained is then purified by chromatography under a nitrogen pressure of 40 kPa, on a silica gel column (particle size 40-63 μ; 3 cm, silica height 27 cm), eluting with a mixture of 28% dichloromethane-methanol-ammonia (14/4 / 0.6 volumes) and collecting 15 cm3 fractions. Fractions 7 to 16 are evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 0.30 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1-β- (5-chlorothien) -acetate are obtained. 2-yl)] piperidine-3-carboxylic acid, as a white meringue. Spectrum of R.M.N. H (300 MHz, (CD3) 2SO d6, δ in ppm). A mixture of two diastereoisomers is observed: from 1.40 to 3.10 (mts: 16H); 3.92 and 3.95 (2 s: 3H in total); 5.23 (mt: 1H); 5.50 (mt: 1H); from 7.05 to 7.15 (mt: 2H); from 7.30 to 7.45 (mt: 2H); 7.52 and 7.54 (2d, J = 5Hz: 1H in total); 7.94 (mt: 1H); 8.70 (d, J = 5 Hz: 1H). (3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinin-4-yl) propyl] -1- [2- (5-chlorothien-2-yl)] piperidine Methyl 3-carboxyIate

Une solution de 1 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-carboxyIate de méthyle dans 40 cm3 d’acétonitrile et 10 cm3 deméthanol est agitée à une température voisine de 20°C, puis additionnée de 1,16 g de 15 carbonate de potassium et 0,5 g d’iodure de potassium. A la suspension obtenue, onajoute 1 g de 2-chloro-5-(2-chloroéthylthio)thiophène et 10 cm3 d’acétonitrile. Lemélange est agité pendant 72 heures à une température voisine de 80°C. La masseréactionnelle est versée sur 75 cm3 d’acétate d’éthyle, puis lavée par 3 fois 70 cm3d’eau. La phase organique est séchée sur 20 sulfate de sodium, filtrée, évaporée sous pression réduite (5 kPa) à une températurevoisine de 45°C. Le résidu obtenu est purifié par chromatographie sous une pressiond’azote de 40 kPa sur une colonne de gel de silice (granulométrie 20-40μ ; diamètre 3,5 cm ; hauteur silice 31 cm), en éluant par de l’acétate d’éthyle et en recueillant desfractions de 30 cm3. Les fractions 24 à 52 sont réunies et concentrées sous pression 25 réduite (5 kPa) à une température voisine de 40°C. On obtient 0,48 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(5-chlorothién-2-yl)]pipéridine-3-carboxylate de méthyle, sous forme d’une huile de couleur brune.A solution of 1 g of methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxyate in 40 cm 3 of acetonitrile and 10 cm3 of methanol are stirred at a temperature of 20 ° C, then added 1.16 g of potassium carbonate and 0.5 g of potassium iodide. To the suspension obtained, 1 g of 2-chloro-5- (2-chloroethylthio) thiophene and 10 cm3 of acetonitrile are added. The mixture is stirred for 72 hours at a temperature of 80 ° C. The reaction mass is poured over 75 cm3 of ethyl acetate, and then washed with 3 times 70 cm3 of water. The organic phase is dried over sodium sulfate, filtered, evaporated under reduced pressure (5 kPa) at a temperature of 45 ° C. The residue obtained is purified by chromatography under nitrogen pressure of 40 kPa on a column of silica gel (particle size 20-40μ, diameter 3.5 cm, silica height 31 cm), eluting with ethyl acetate. and collecting fractions of 30 cm3. Fractions 24 to 52 are combined and concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 0.48 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (5-chlorothien)] are obtained. 2-yl)] Piperidine-3-carboxylic acid methyl ester as a brown oil.

Spectre de masse : (IC) m/z : 535 MH* * 2-,Chloro-5-(2-chloroéthylthio)thiophène 30 A une solution de 17,9 g de 2-chloro-5-thiophènethiol dans 30 cm3 de l-chloro-2-bromoéthane refroidi à une température voisine de 5°C, on ajoute sous agitation 120 2 2 241 28 cm3 d’une solution aqueuse de soude 5N, puis on laisse revenir la température auvoisinage de 20°C, tandis que l’agitation est poursuivie pendant 16 heures. Lemélange réactionnel est dilué par 300 cm3 d’acétate d’éthyle, lavé par 3 fois 150 cm3d’eau. La solution organique est séchée sur sulfate de sodium, filtrée, évaporée souspression réduite (5 kPa) à une température voisine de 45 °C. On obtient 20,6 g de2-chloro-5-(2-chloroéthylthio)thiophène, sous forme d’une huile de couleur brune.Spectre de masse : DCI m/z = 535 MH*Mass Spectrum: (CI) m / z: 535 MH + 2-, Chloro-5- (2-chloroethylthio) thiophene To a solution of 17.9 g of 2-chloro-5-thiophenethiol in 30 cc 2-chloro-2-bromoethane cooled to a temperature of 5 ° C, is added with stirring 120 2 241 28 cm3 of a 5N aqueous sodium hydroxide solution, then the temperature is allowed to return to the vicinity of 20 ° C, while the stirring is continued for 16 hours. The reaction mixture is diluted with 300 cm3 of ethyl acetate, washed with 3 times 150 cm3 of water. The organic solution is dried over sodium sulphate, filtered and evaporated under reduced pressure (5 kPa) at a temperature in the region of 45 ° C. 20.6 g of 2-chloro-5- (2-chloroethylthio) thiophene are obtained in the form of a brown oil. Mass spectrum: DCI m / z = 535 MH *

Le 2-chloro-5-thiophénethiol peut être préparé selon E. JONES et M. MOODIE,Tetrahedron, 1965, vol. 21, 1333-1336.2-Chloro-5-thiophenethiol can be prepared according to E. JONES and M. MOODIE, Tetrahedron, 1965, vol. 21, 1333-1336.

Exemple 46Example 46

Acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-fluoro-3- phénylpropyl] pipéridine-3-carboxyiique.(3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3-fluoro-3-phenylpropyl] piperidine-3-carboxylic acid.

Un mélange de 0,4 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(3-(R,S)-fluoro-3-phénylpropyl]pipéridine-3-carboxylate de méthyle et 0,18 g de monohydratehydroxyde de lithium dans 2 cm3 d’eau et 10 cm3 d’acétone est agité pendant 3 jours àune température voisine de 20°C, puis évaporé sous pression réduite (5 kPa) à unetempérature voisine de 40°C. Le résidu obtenu est purifié par chromatographie sousune pression d’argon de 50 kPa, sur une colonne de gel de silice (granulométrie 20-45p ; diamètre 3 cm ; 50 g), en éluant par un mélange de dichlorométhane-méthanol(95/5 en volumes) et en recueillant d’aboid une fraction de 910 cm3. Puis on élue parun mélange de dichlorornéthane-méthanol (90/10 en volumes) et en recueillant desfractions de 13 cm3. Les fractions 47 à 69 sont réunies puis évaporées sous pressionréduite (5 kPa) à une température voisine de 40°C. Le résidu d’évaporation est reprispar du dichlorométhane, filtré, concentré dans les mêmes conditions que ci-dessus. Leproduit obtenu est agité pendant 10 minutes dans 10 cm3 d’éther diisopropylique. Lescristaux sont filtrés, lavés par 1 fois 5 cm3 d’éther diisopropylique et 3 fois 5 cm3 depentane. On obtient 0,102 g d’acide (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-fluoro-3-phénylpropyl]pipéridine-3-carboxylique, sous forme d’un solide decouleur grise fondant à 60°C, et correspondant à l'un des diastéréoisomères.oto20 =+37,5 +/-0,9 dans le mélhanol à 0,5%. 120 22 242A mixture of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (R, S) -fluoro-3-phenylpropyl] piperidine, (0.4 g) Methyl 3-carboxylate and 0.18 g of lithium monohydratehydroxide in 2 cm3 of water and 10 cm3 of acetone is stirred for 3 days at a temperature in the region of 20 ° C. and then evaporated under reduced pressure (5 kPa) at room temperature. close to 40 ° C. The residue obtained is purified by chromatography under an argon pressure of 50 kPa, on a silica gel column (particle size 20-45p, diameter 3 cm, 50 g), eluting with a mixture of dichloromethane -methanol (95/5 by volume) and collecting aboid a fraction of 910 cm3, then eluted with a mixture of dichloromethane-methanol (90/10 by volume) and collecting fractions of 13 cm3. are combined and then evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. The evaporation residue is taken up in dichloromethane, filtered, concentrated under the same conditions as above The product obtained is stirred for 10 minutes in 10 cm3 of diisopropyl ether. The crystals are filtered, washed with 1 x 5 cm 3 of diisopropyl ether and 3 x 5 cm 3 of depentane. 0.102 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3-fluoro-3-phenylpropyl] piperidine-3-carboxylic acid are obtained in the form of a gray solid mass melting at 60 ° C. and corresponding to one of the diastereoisomers. O 20 = + 37.5 +/- 0.9 in 0.5% melanol. 120 22 242

Spectre de R.M.N. ’H (300 MHz, (CD3)2SO d6, δ en ppm) : de 1,45 à 3,10 (mts :16H) ; 3,02 (t large, J = 7 Hz : 2H) ; 4,04 (s : 3H) ; 5,59 (mt, JHF = 48 Hz : 1H) ; 7,32(d, J = 4,5 Hz : 1H) ; de 7,35 à 7,50 (mt : 7H) ; 7,42 (d, J = 9 Hz : 1H) ; 8,62 (d, J = 4,5 Hz : 1H). (3R,4R)-4-[3-(6-MéthoxyquinoIin-4-yl)propyI]-l-(3-(RS)-fluoro-3- phénylpropyl]pipéridine-3-carboxylate de méthyle A une solution agitée de 1,18 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(R,S)-hydroxy-3-phénylpropyl]pipéridine-3-carboxyIate de méthyle dans 17,7 cm3de dichlorométhane, on ajoute sous atmosphère inerte à une température voisine de20°C 0,425 cm3 de diéthylaminosulfure trifluorure. Après 3 heures d’agitation, lemélange est versé sur 32 cm3 d’une solution aqueuse saturée d’hydrogénocarbonate desodium. On ajoute 15 cm3 de dichlorométhane, puis on agite le mélange pendantencore 10 minutes. Après décantation, la phase organique est séparée, tandis que laphase aqueuse est extraite par 3 fois 10 cm3 de dichlorométhane. Les extraitsorganiques sont réunis, lavés par 3 fois 20 cm3 d’eau, séchés sur sulfate de sodium,filtrés, concentrés sous pression réduite (5 kPa) à une température voisine de 40°C.On obtient 1,11g d’un résidu que l’on purifie par chromatographie sous une pressiond’argon de 50 kPa, sur une colonne de silice (granulométrie 20-45μ ; diamètre 2,8 cm ; 45 g silice), en éluant par un mélange d’acétate d’éthyle-méthanol (98/2 envolumes), et en recueillant des fractions de 15 cm3. Les fractions 10 à 20 sont réuniespuis évaporées sous pression réduite (5 kPa) à une température voisine de 40°C. Onobtient 0,6 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(RS)-fluoro-3-phénylpropyl]pipéridine-3-carboxylate de méthyle, sous forme d’une huile épaisse decouleur jaune clair.Spectrum of R.M.N. H (300 MHz, (CD3) 2SO d6, δ in ppm): from 1.45 to 3.10 (mts: 16H); 3.02 (broad t, J = 7 Hz: 2H); 4.04 (s: 3H); 5.59 (mt, JHF = 48 Hz: 1H); 7.32 (d, J = 4.5 Hz: 1H); from 7.35 to 7.50 (mt: 7H); 7.42 (d, J = 9 Hz: 1H); 8.62 (d, J = 4.5 Hz: 1H). Methyl (3R, 4R) -4- [3- (6-Methoxyquinyl-4-yl) propyl] -1- (3- (RS) -fluoro-3-phenylpropyl] piperidine-3-carboxylate To a stirred solution of 1.18 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (R, S) -hydroxy-3-phenylpropyl] piperidine-3-carboxyIate of methyl in 17.7 cm3 of dichloromethane, 0.425 cm3 of diethylaminosulfide trifluoride are added under an inert atmosphere at a temperature of 20 ° C. After stirring for 3 hours, the mixture is poured into 32 cm 3 of a saturated aqueous solution of sodium hydrogencarbonate. 15 cm3 of dichloromethane are added, and the mixture is then stirred for a further 10 minutes After decantation, the organic phase is separated, while the aqueous phase is extracted with dichloromethane (3 × 10 cm 3) .The organic extracts are combined, washed 3 × cm 3 of water, dried over sodium sulphate, filtered, concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 1.11 g of a res idu that is purified by chromatography under an argon pressure of 50 kPa, on a silica column (granulometry 20-45μ; diameter 2.8 cm; 45 g silica), eluting with a mixture of ethyl acetate-methanol (98/2 volumes), and collecting 15 cm3 fractions. Fractions 10 to 20 are combined and then evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 0.6 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (RS) -fluoro-3-phenylpropyl] piperidine-3-carboxylate are obtained from methyl, in the form of a light yellow thick oil.

Spectre infra rouge (CH2CI2) : 2951 ; 1732 ; 1621 ; 1509 ; 1473 ; 1227 ; 1167 ; 1031et 848 cm'1Infra red spectrum (CH 2 Cl 2): 2951; 1732; 1621; 1509; 1473; 1227; 1167; 1031and 848 cm'1

Le (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(R,S)-hydroxy-3-phényl-propyl]pipéridine-3-carboxyIate de méthyle peut être préparé par analogie avec laméthode décrite dans l’exemple 2.Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (R, S) -hydroxy-3-phenylpropyl] piperidine-3-carboxyIate can be prepared by analogy with the method described in Example 2.

Exemple 47 1Example 47

Trichlorhydrate de l’acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yI)propylJ-l-[2-(pyridin-2-yIthio)éthylJpipéridine-3-carboxylique 243 12 0 2 2 A une solution de 0,33 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(pyridin-2-ylthio)éthyl]pipéridine-3-carboxylate de méthyle dans 6,66 cm3 de méthanol maintenue à une température voisine de 20°C, on ajoute sousagitation et sous atmosphère d’azote 1,33 cm3 d’une solution aqueuse de soude 5N.La solution obtenue est chauffée au voisinage de 60°C pendant 16 heures. La masseréactionnelle est évaporée à sec sous pression réduite (5 kPa) à une températurevoisine de 60°C. Le résidu obtenu est repris dans 3,4 cm3 d’eau distillée, puisadditionné de 3,43 cm3 d’acide chlorhydrique aqueux concentré à 36 %. On obtientune solution de couleur jaune que l’on évapore dans les mêmes conditions queprécédemment. Le résidu d’évaporation est repris dans 10 cm3 d’un mélange dedichlorométhane-méthanol (80/20 en volumes). L’insoluble qui en résulte est filtré,lavé par 2 fois 2,5 cm3 d’un mélange de dichlorométhane-méthanol (90/10 envolumes). Le filtrat est évaporé sous pression réduite (5 kPa) à une températurevoisine de 40°C. On obtient 0,40 g de trichlorhydrate de l’acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yi)propyl]-l-[2-(pyridin-2-yIthio)éthyl]pipéridine-3-carboxylique, sous forme d’un solide de couleur beige fondant à 155°C.(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-ylthio) ethyl] piperidine hydrochloride trihydrochloride -3-carboxylic acid 243 12 0 2 2 To a solution of 0.33 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] Methyl 1- [2- (pyridin-2-ylthio) ethyl] piperidine-3-carboxylate in 6.66 cm3 of methanol maintained at a temperature of 20 ° C, is added under stirring and under a nitrogen atmosphere 1, 33 cm 3 of a 5N aqueous sodium hydroxide solution. The solution obtained is heated to around 60 ° C. for 16 hours. The reaction mass is evaporated to dryness under reduced pressure (5 kPa) at a temperature of about 60.degree. The residue obtained is taken up in 3.4 cm3 of distilled water, and thenadditioned with 3.43 cm3 of 36% concentrated aqueous hydrochloric acid. A yellow solution is obtained which is evaporated under the same conditions as above. The evaporation residue is taken up in 10 cm3 of a dichloromethane-methanol mixture (80/20 by volume). The resulting insoluble matter is filtered, washed with 2.5 cm3 of a mixture of dichloromethane-methanol (90/10 volumes). The filtrate is evaporated under reduced pressure (5 kPa) at a temperature of 40 ° C. 0.40 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (3R, 4R)) trihydrochloride is obtained. (pyridin-2-ylthio) ethyl] piperidine-3-carboxylic acid as a beige colored solid melting at 155 ° C.

Spectre de R.M.N. (400 MHz, (CD3)2SO d6, à une température de 383K, δ enppm). On observe un mélange de deux diastéréoisomères : de 1,50 à 2,30 et de 3,15 à 3,65 (mts : 16H) ; 4,00 (s : 3H) ; 5,38 (mt : 1H) ; 7,18 (ddlarge, J = 8 et 5 Hz : 1H) ; 7,38 (d, J - 8 Hz : 1H) ; de 7,5:. à 7,65 (mt : 2H) ; 7,69 (t,J - 8 et 2 Hz : 1H) ; 7,80 (mt : IB) ; 8,20 (d large, J - 10 Hz : 1H) ; 8,48 (dmt, J = 5Hz : 1H) ; 8,35 (d large, J = 5 Hz : 1H). (3R,4R)-4-[3-(R,S)-Hydroxy-3-(6-méthoxyquinolin-4-yl)propyl)-l-[2-(pyridïn-2-ylthio)éthyl]pipéridine-3~carboxylate de méthyleSpectrum of R.M.N. (400 MHz, (CD3) 2SO d6, at a temperature of 383K, δ enppm). A mixture of two diastereoisomers: from 1.50 to 2.30 and from 3.15 to 3.65 (mts: 16H); 4.00 (s: 3H); 5.38 (mt: 1H); 7.18 (ddlarge, J = 8 and 5 Hz: 1H); 7.38 (d, J - 8 Hz: 1H); 7.5 :. at 7.65 (mt: 2H); 7.69 (t, J - 8 and 2 Hz: 1H); 7.80 (mt: 1H); 8.20 (broad d, J - 10 Hz: 1H); 8.48 (dmt, J = 5Hz: 1H); 8.35 (broad d, J = 5 Hz: 1H). (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl) -l- [2- (pyridin-2-ylthio) ethyl] piperidin-3 methyl carboxylate

Une solution agitée de 0,77 g de (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(pyridin-2-ylthio)éthyl]pipéridine-3-carboxylate de méthyle dans15 cm3 de méthanol est refroidie à une température voisine de 0°C sous atmosphèreinerte. On ajoute 0,063 g de borohydrure de sodium, puis après 15 minutes latempérature est ramenée au voisinage de 20°C pendant 16 heures. Après addition de5 cm3 d’une solution aqueuse saturée de chlorure d’ammonium, le mélange est agitépendant 10 minutes, puis évaporé sous pression réduite (5 kPa) à une températurevoisine de 40°C. Le résidu obtenu est repris dans 10 cm3 d’un mélange dedichlorométhane-méthanol (95/5 en volumes), puis filtré. L’insoluble est lavé par 120 22 244 2 fois 5 cm3 du même mélange. Le filtrat est évaporé dans les mêmes conditions queci-dessus. On obtient une meringue que l’on purifie par chromatographie sous unepression d’azote de 100 kPa, sur une colonne de gel de silice (granulométrie 40-63μ ;diamètre 3,5 cm ; hauteur silice 35 cm) en éluant d’abord par un mélange de 5 dichlorométhane-méthanol (96/4 en volumes), et en recueillant des fractions de35 cm3. Après les 50 premières fractions, on élue par un mélange de dichlorométhane-méthanol (90/10 en volumes). Les fractions 61 à 90 sont réunies puis évaporées souspression réduite (5 kPa) à une température voisine de 40°C. On obtient 0,33 g de(3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(pyridin-2- 10 ylthio)éthyl]pipéridine-3-carboxylate de méthyle, sous forme d’une laque de couleurbeige.A stirred solution of (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-ylthio) ethyl) 0.77 g Piperidine-3-carboxylate methyl in 15 cm3 of methanol is cooled to a temperature of 0 ° C under atmosphere. 0.063 g of sodium borohydride is added, then after 15 minutes the temperature is reduced to around 20 ° C. for 16 hours. After addition of 5 cm3 of a saturated aqueous solution of ammonium chloride, the mixture is stirred for 10 minutes and then evaporated under reduced pressure (5 kPa) at a temperature of 40 ° C. The residue obtained is taken up in 10 cm3 of a mixture of dichloromethane-methanol (95/5 by volume), and then filtered. The insoluble material is washed twice with 5 cm 3 of the same mixture. The filtrate is evaporated under the same conditions as above. A meringue is obtained which is purified by chromatography under a nitrogen pressure of 100 kPa, on a column of silica gel (particle size 40-63μ, diameter 3.5 cm, silica height 35 cm), eluting first with a mixture of dichloromethane-methanol (96/4 by volume), and collecting 35 cm3 fractions. After the first 50 fractions, eluted with a mixture of dichloromethane-methanol (90/10 by volume). Fractions 61 to 90 are combined and then evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 0.33 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2) are obtained. Methyl (methyl) piperidine-3-carboxylate in the form of a dye-colored lacquer.

Spectre infra rouge (CH2C12) : 2596 ; 2951 ; 1622 ; 1579 ; 1508 ; 1455 ; 1415 ; 1242 ;1228 ; 1125 ; 1031 ; 856 et 831 cm'' (3R,4R)-4-[3-Oxo-3-(6-méthoxyquinolin-4-yI)propyl]-l-[2-(pyridin-2-15 ylthio)éthyl]pipéridine-3-carboxylate de méthyleInfra red spectrum (CH 2 Cl 2): 2596; 2951; 1622; 1579; 1508; 1455; 1415; 1242; 1228; 1125; 1031; 856 and 831 cm -1 (3R, 4R) -4- [3-Oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-ylthio) ethyl] piperidine- Methyl 3-carboxylate

Un mélange de 1,35 g de dichlorhydrate de (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin- 4-yl)propyl]-l-(2-chloroéthyl)pipéridine-3-carboxylate de méthyle dans 20 cm3d’acétonitrile est agité à une température voisine de 20°C sous atmosphère inerte. Onajoute 1,37 g de carbonate de potassium et 0,456 g d’iodure de potassium, puis 20 0,367 g de 2-mercaptopyridine et 1 cm3 de méthanol. On obtient une suspension rouge que l’on chauffe à une température voisine de 80°C pendant 1 heure 30minutes. Après refroidissement de la masse réactionnelle à une température voisine de20°C, l’insoluble est filtré, lavé par de l’acétonitrile. Le filtrat est évaporé souspression réduite (5 kPa) à une température voisine de 40°C. Le résidu d’évaporation 25 est purifié par chromatographie sous une pression d’azote de 100 kPa, sur unecolonne de gel de silice (granulométrie 40-63μ ; diamètre 3,5 cm ; hauteur silice35 cm), en éluant par un mélange d’acétate d’éthyle-méthanol (95/5 en volumes) et enrecueillant des fractions de 35 cm3. Les fractions 19 à 40 sont réunies puis évaporéessous pression réduite (5 kPa) à une température voisine de 40°C. On obtient 0,77 g de 30 (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(pyridin-2- ylthio)éthyl]pipéridine-3-carboxylate de méthyle, sous forme d’une huile visqueusede couleur rouge. 120 2 2 245A mixture of 1.35 g of (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (2-chloroethyl) piperidine-3-carboxylate dihydrochloride from Methyl in 20 cm3 of acetonitrile is stirred at a temperature of 20 ° C under an inert atmosphere. 1.37 g of potassium carbonate and 0.456 g of potassium iodide are added, followed by 0.367 g of 2-mercaptopyridine and 1 cm3 of methanol. A red suspension is obtained which is heated at a temperature in the region of 80 ° C. for 1 hour 30 minutes. After cooling the reaction mass to a temperature of 20 ° C, the insoluble material is filtered and washed with acetonitrile. The filtrate is evaporated under reduced pressure (5 kPa) at a temperature of 40 ° C. The evaporation residue is purified by chromatography under a nitrogen pressure of 100 kPa, on a column of silica gel (particle size 40-63 μ, diameter 3.5 cm, silica height 35 cm), eluting with a mixture of ethyl acetate-methanol (95/5 by volume) and containing fractions of 35 cm3. Fractions 19 to 40 are combined and then evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 0.77 g of (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-ylthio) ethyl] piperidine are obtained. Methyl-3-carboxylate, in the form of a viscous red oil. 120 2 2 245

Spectre infra rouge (CHjCy : 2952 ; 2S09 ; 1733 ; 1692 ; 1620 ; 1580 ; 1455 ; 1415 ;1243; 1125; 1029 et 853 cm'1Infra red spectrum (CH 2 Cl 2: 2952; 2SO9; 1733; 1692; 1620; 1580; 1455; 1415; 1243; 1125; 1029 and 853 cm -1;

Le (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(pyridin-2-ylthio) éthyl]pipéridine-3-carboxylate de méthyle est préparé par analogie avec la méthodedécrite dans l'exemple 21.Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-ylthio) ethyl] piperidine-3-carboxylate is prepared by analogy with the method described in Example 21.

Exemple 48Example 48

Dichlorhydrate de l’acide (3R,4R)-4-[3-hydroxy-3-(6-méthoxyquinolin-4-yl)propyIJ-l-[2-(2-thiényIthio)éthyl]pipéridine-3-acétique, diastéréoisomère A etacide (3R,4R)-4-[3-hydroxy-3-(6-méthoxyquinolin-4-yi)propyl]-l-[2-(2- thiényIthio)éthyl]pipéridine-3-acétique, diastéréoisomère B. 1,2 g d’acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2-thiénylthio)éthyl]pipéridine-3-acétique est chromatographié sur une colonne de35 cm de long et 6 cm de diamètre, conditionnée avec 700 g de silice Kromasil®-CN(granulométrie 10μ). L’élution est effectuée à l’aide d’un mélange de dichloro-méthane-éthanol-triétylamine (98/2/0,1 en volumes) Le débit est de 70 cnP/minute.La détection est effectuée en ultra violet à 265 nm, Après plusieurs injectionspréparatives, on recueille les fractions correspondant au diastéréoisomère A. Celles-cisont concentrées sous pression réduite (5 kPa) à une. température voisine de 40°C. Onobtient 0,34 g d’un produit que l’on salifie de la façon suivante : 0,3 g de ce produitest repris dans 30 cm3 d'éther, filtré pv;s dissous dans 25 cm3 d’acétone. La solutionobtenue est versée sur 5 cm3 d’éther chlorhydrique 5N. Après concentration dumélange sous pression réduite dans les mêmes conditions que ci-dessus, le résiduobtenu est repris par 20 cm3 d’eau, la solution lyophilisée. On obtient 0,190 g dedichlorhydrate de l’acide (3R,4R)-4-[3-hydroxy-3-(6-méthoxyquinoiin-4-yl)propyl]-l-[2-(2-thiénylthio;éthyl]pipéridine-3-acétique, diastéréoisomère A, sous forme d’unlyophilisât de couleur orangée. Au cours de la séparation préparative des deuxdiastéréoisomères, les fractions-mélange sont concentrées comme ci-dessus pour unretraitement. Les conditions de séparation sont les suivantes : colonne de 35 cm delong et 6 cm de diamètre, conditionnée avec 700 g de silice Kromasil®(granulométrie lOu). L’élution est effectuée à l’aide d’un mélange dedichlorométhane-acétonitrile-méhanol-triétylamine (60/40/4/0,1 en volumes) Le débitest de 80 cm3/minute. Après 3 injections préparatives on recueille les fractionscorrespondant au diastéréoisomère B. Celles-ci sont concentrées dans les mêmes 246 120 22 conditions que ci-dessus. On obtient 0,34 g d’acide (3R,4R).-4-[3-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2-thiénylthio) éthyl]pipéridine-3-acétique, diastéréoisomère B, sous forme d’une meringue de couleur jaune. (aD20 =+55,4 +/-1,1dans le dichlorométhane à 0,5 %). diastéréoisomère A : Spectre de R.M.N. (400 MHz, (CD3)2SO d6 avec ajout dequelques gouttes de CD3COOD d4 à une température de 373K, δ en ppm) : de 1,40 à1,90 et de 2,20 à 2,55 (mts : 10H) ; de 2,95 à 3,35 (mt : 8H) ; 3,99 (s : 3H) ; 5,40 (mt :1H) ; 7,07 (dd, J = 5,5 et 3,5 Hz : 1H) ; 7,27 (d large, J = 3,5 Hz : 1H) ; de 7,55 à 7,65(mt : 3H) ; 7,85 (d, J = 4,5 Hz : 1H) ; 8,17 (d, J = 9 Hz : 1H) ; 8,88 (d, J = 4,5 Hz :1H). diastéréoisomère B : Spectre de R.M.N. ^H (250 MHz, (CD3)2SO d6, δ en ppm) : de1,20 à 2,80 (mts : 16H) ; 2,88 (t large, J = 7 Hz : 2H) ; 3,92 (s : 3H) ; 5,27 (mt : 1H) ;7,04 (dd, J = 5,5 et 3,5 Hz : 1H) ; 7,17 (dd, J = 3,5 et 1,5 Hz : 1H) ; de 7,30 à 7,45(mt : 2H) ; 7,54 (d, J = 4,5 Hz : 1H) ; 7,60 (dd, J = 5,5 et 1,5 Hz : 1H) ; 7,94 (d,J = 9,5 Hz : 1H) ; 8,71 (d, J = 4,5 Hz : 1H).(3R, 4R) -4- [3-Hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-acetic acid dihydrochloride, diastereoisomer dihydrochloride (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-acetic acid, diastereoisomeric B. 1.2 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) acid) ethyl] piperidine-3-acetic acid is chromatographed on a column 35 cm long and 6 cm in diameter, conditioned with 700 g of Kromasil®-CN silica (particle size 10 μ). The elution is carried out using a mixture of dichloromethane-ethanol-trietylamine (98/2 / 0.1 by volume). The flow rate is 70 cnP / minute. The detection is carried out in ultra violet at 265 ° C. After several preparative injections, the fractions corresponding to the diastereoisomer A are collected. Those fractions are concentrated under reduced pressure (5 kPa) at 1 ° C. temperature close to 40 ° C. 0.34 g of a product which is salified as follows: 0.3 g of this product is taken up in 30 cm3 of ether, filtered and dissolved in 25 cm3 of acetone. The solution obtained is poured into 5 cm3 of 5N hydrochloric ether. After concentration of the mixture under reduced pressure under the same conditions as above, the residue obtained is taken up in 20 cm3 of water, the freeze-dried solution. 0.190 g of (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine acid dihydrochloride is obtained. 3-acetic acid, diastereoisomer A, in the form of an orange-colored lyophilisate During the preparative separation of the two diastereoisomers, the mixture-fractions are concentrated as above for a treatment.The separation conditions are as follows: 35 cm column Delong and 6 cm in diameter, conditioned with 700 g of Kromasil® silica (particle size 10u) elution is carried out using a mixture of dichloromethane-acetonitrile-methanol-triethylamine (60/40/4 / 0.1 in volume) The flow rate is 80 cm3 / minute After 3 preparative injections, the fractions corresponding to diastereoisomer B are collected .They are concentrated in the same conditions as above, to give 0.34 g of acid ( 3R, 4R) .- 4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -l- [2- (2-thienylthio) ethyl] piperidine-3-acetic acid, diastereoisomer B, in the form of a yellow meringue. (aD20 = + 55.4 +/- 1.1 in 0.5% dichloromethane). diastereoisomer A: Spectrum of R.M.N. (400 MHz, (CD3) 2SO d6 with the addition of some drops of CD3COOD d4 at a temperature of 373K, δ in ppm): from 1.40 to 1.90 and from 2.20 to 2.55 (mts: 10H); from 2.95 to 3.35 (mt: 8H); 3.99 (s: 3H); 5.40 (mt: 1H); 7.07 (dd, J = 5.5 and 3.5 Hz: 1H); 7.27 (broad d, J = 3.5 Hz: 1H); 7.55 to 7.65 (mt: 3H); 7.85 (d, J = 4.5 Hz: 1H); 8.17 (d, J = 9 Hz: 1H); 8.88 (d, J = 4.5 Hz: 1H). diastereoisomer B: Spectrum of R.M.N. H (250 MHz, (CD3) 2SO d6, δ in ppm): from 1.20 to 2.80 (mts: 16H); 2.88 (broad t, J = 7 Hz: 2H); 3.92 (s: 3H); 5.27 (mt: 1H), 7.04 (dd, J = 5.5 and 3.5 Hz: 1H); 7.17 (dd, J = 3.5 and 1.5 Hz: 1H); from 7.30 to 7.45 (mt: 2H); 7.54 (d, J = 4.5 Hz: 1H); 7.60 (dd, J = 5.5 and 1.5 Hz: 1H); 7.94 (d, J = 9.5 Hz: 1H); 8.71 (d, J = 4.5 Hz: 1H).

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoIin-4-yl)propyI]-l-[2-(2-thiényIthio)éthyl]pipéridine-3-acétique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3- acid acetic

Un mélange de 0,22 g de dichlorhydrate de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoIin-4-yl)propyl]-l-[2-(2-thiénylthio)éthyl]pipéridine-3-acétate deméthyle dans 5 cm3 de dioxanne, additionné de 0,683 cm3 de soude aqueuse 5N, estagité pendant 20 heures à une température voisine de 60°C. Après évaporation souspression réduite (5 kPa) à une température voisine de 40°C, le résidu obtenu estpurifié par chromatographie à pression atmosphérique sur une colonne de gel de silice(granulométrie 20-45μ ; diamètre 1 cm ; volume de silice 20 cm3) en éluant par unmélange de chloroforme-méthanol-ammoniaque (12/3/1 en volumes). Les fractions 1à 3 sont réunies, concentrées dans les conditions de ci-dessus. On obtient un produitque l’on sèche à l’étuve à poids constant sous pression réduite (10 Pa) à unetempérature voisine de 40°C. On obtient 0,179 g d’acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2-thiénylthio)éthyl]pipéridine-3-acétique, sous forme d’une meringue blanche qui est un mélange de deuxdiastéréoisomères.A mixture of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinin-4-yl) propyl] -1- [2- (2H) dihydrochloride is preferably -thienylthio) ethyl] piperidine-3-methyl acetate in 5 cm3 of dioxane, added with 0.683 cm3 of 5N aqueous sodium hydroxide, is stirred for 20 hours at a temperature in the region of 60 ° C. After evaporation under reduced pressure (5 kPa) at a temperature in the region of 40 ° C., the residue obtained is purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45 μ, diameter 1 cm, volume of silica 20 cm 3) in eluent with a mixture of chloroform-methanol-ammonia (12/3/1 by volume). Fractions 1 to 3 are combined, concentrated under the conditions of above. A product is obtained which is dried in an oven at constant weight under reduced pressure (10 Pa) at a temperature of 40 ° C. 0.179 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) acid is obtained. ethyl] piperidine-3-acetic acid, in the form of a white meringue which is a mixture of two diastereoisomers.

II

Spectre de R.M.N. ^H (300 MHz, (CD3)2SO d6, δ en ppm). On observe un mélangede deux diastéréoisomères : 247 12 0 2 2 de 1,15 à 2,80 (mis : 16H) ; 2,88 (t large, J = 7 Hz : 2H) ; 3,91 et 3,92 (2s : 3H entotalité) ; 5,26 (mf : 1H) ; 5,53 (mt : 1H) ; 7,04 (dd, J - 5,5 et 3,5 Hz : 1H) ; 7,36 (dd,J = 3,5 et 1 Hz : 1 H) ; de 7,30 à 7,45 (mt ; 2H) ; de 7,54 (mt : 1H) ; 7,60 (d large, J = 5,5 Hz : 1H) ; 7,94 (d, J = 9 Hz : 1H) ; 8,70 (d, J = 4,5 Hz : 1H).Spectrum of R.M.N. ^ H (300 MHz, (CD3) 2SO d6, δ in ppm). A mixture of two diastereoisomers is observed: 247 12 0 2 2 from 1.15 to 2.80 (mis: 16H); 2.88 (broad t, J = 7 Hz: 2H); 3.91 and 3.92 (2s: 3H entotality); 5.26 (mf: 1H); 5.53 (mt: 1H); 7.04 (dd, J - 5.5 and 3.5 Hz: 1H); 7.36 (dd, J = 3.5 and 1 Hz: 1H); from 7.30 to 7.45 (mt; 2H); 7.54 (mt: 1H); 7.60 (broad, J = 5.5 Hz: 1H); 7.94 (d, J = 9 Hz: 1H); 8.70 (d, J = 4.5 Hz: 1H).

Dichlorhydrate de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2-thiényIthio)éthyl]pipéridine-3-acétate de méthyle A une solution de 0,84 g de (3R,4R)-4-[3-oxo-3-(6-niéthoxyquinolin-4-yl)propyl]-l-[2-(2-thiénylthio)éthyl]pipéridine-3-acétate de méthyle dans 12 cm3 de méthanolmaintenue à une température voisine de 20°C, on ajoute sous agitation' 1 goutte desoude aqueuse 5N, puis 0,17 g de borohydrure de sodium par petites fractions. Lemélange est agité pendant 3 heures à une température voisine de 20°C. Après additionde 10 cm3 d’eau, on évapore le méthanol sous pression réduite (5 kPa) à unetempérature voisine de 40°C. Le résidu obtenu est extrait par 2 fois 20 cm3 dedichlorométhane, puis les extraits réunis sont lavés par 2 fois 30 cm3 d’eau, séchés sursulfate de magnésium, filtrés, concentrés sous pression réduite (5 kPa) à unetempérature voisine de 40°C. On obtient une huile que l’on purifie parchromatographie à pression atmosphérique sur une colonne de gel de silice(granulométrie 20-45μ ; diamètre 2,5 cm ; volume silice 150 cm3), en éluant par unmélange de dichlorométhane-méthanol (99/1 en volumes). Les fractions 56 à 115 sontréunies puis concentrées comme ci-dessus. On obtient une huile dont on fait lechlorhydrate de la façon suivante : i’hutl·.·, est solubilisée dans 20 cm3 d’étherdiéthyli'iue, puis veisée sur 2 cm3 d’éther chlorhydrique IN. Le précipité formé estessoré, séché à l’étuve sous pression réduite (10 Pa) à une température voisine de40°C. On obtient 0,3 g de dichlorhydrate de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2-thiénylthio)éthyl)pipéridine-3-acétate de méthyle, sous forme d’un solide blanc.(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-dihydrochloride Methyl acetate To a solution of (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio), 0.84 g) ethyl] piperidine-3-methyl acetate in 12 cm3 of methanol maintained at a temperature of 20 ° C, is added with stirring 1 drop of 5N aqueous dye, then 0.17 g of sodium borohydride in small portions. The mixture is stirred for 3 hours at a temperature of 20 ° C. After addition of 10 cm3 of water, the methanol is evaporated under reduced pressure (5 kPa) at a temperature of 40 ° C. The residue obtained is extracted with 2 times 20 cm3 of dichloromethane, then the combined extracts are washed with 2 times 30 cm3 of water, dried over magnesium sulfate, filtered, concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. An oil is obtained which is purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45μ, diameter 2.5 cm, silica volume 150 cm 3), eluting with a mixture of dichloromethane-methanol (99/1). in volumes). Fractions 56 to 115 are then combined and concentrated as above. An oil is obtained which is made hydrochloride as follows: 1'Hutl · · ·, is solubilized in 20 cm3 of éthherdiéthyliuei, then veillée on 2 cm3 of 1 N hydrochloric ether. The precipitate formed is stripped and dried in an oven under reduced pressure (10 Pa) at a temperature in the region of 40 ° C. 0.3 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2- (2-dihydrochloride) salt are obtained. thienylthio) ethyl) piperidine-3-methyl acetate as a white solid.

Spectre de R.M.N. ^H (400 MHz, (CD3)2SO d6 à une température de 383K, δ enppm). On observe un mélange de deux diastéréoisomères : de 1,40 à 2,00 et de 2,25 à 2,70 (mts : 10H en totalité) ; de 2,90 à 3,40 (mf : 4H) ; 3,27(mt : 4H) ; 3,61 et 3,63 (2s : 3H en totalité) ; 4,00 (s : 3H) ; 5,38 (mt : 1H) ; 7,10 (dd,J = 5 et 3,5 Hz : 1 H) ; 7,29 (d large, J = 3,5 Hz : 1H) ; de 7,55 à 7,60 (mt : 2H) ; 7,65(d, J = 5 Hz : 1H; ; 7,76 (mt : 1H) ; 8,16 (d, J = 9,5 Hz : 1H) ; 8,85 (d, J - 4,5 Hz : 1H). 120 22 248 (3R,4R)-4-[3-Oxo-3-(6-méthoxyquinolin-4-yl)propyI]-l-(2-(2-thiényIthio)éthyI]pipéridine-3-acétate de méthyle A une solution de 2,8 g de (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-acétate de méthyle dans 60 cm3 d’acétonitrile on ajoute à unetempérature voisine de 20°C, sous agitation, 1,5 g de 2-(2-chloroéthylthio)thiophène,puis 5,2 g de carbonate de potassium et 2,5 g d’iodure de potassium. Le mélange estchauffé pendant 20 heures à une température voisine du reflux, puis refroidi auxenvirons de 20°C. On ajoute 130 cm3 d’eau et 50 cm3 d’acétate d’éthyle au mélangeréactionnel. Après décantation du mélange, la phase organique est lavée par 150 cm3d’eau, séchée sur sulfate de magnésium, filtrée puis concentrée sous pression réduite(5 kPa) à une température voisine de 40°C. On obtient une huile que l’on purifie parchromatographie à pression atmosphérique sur une colonne de gel de silice(granulométrie 20-45μ ; diamètre 2,5 cm ; volume silicelOO cm3) en éluant par unmélange de dichlorométhane-méthanol (95/5 en volumes). On recueille d’abord unefraction de 30 cm3, puis des fractions d’environ 10 cm3. Les fractions 1 à 4 sontréunies, puis évaporées comme précédemment. On obtient 2,3 g d’une huile bruneque l’on soumet une seconde fois à une purification par chromatographie à pressionatmosphérique sur une colonne de gel de silice (granulométrie 20-45μ ; diamètre 2,5 cm ; volume silice 300 cm3), en éluant par un mélange de dichlorométhane-méthanol (99/1 en volumes) et en recueillant des fractions de 10 cm3 environ. Lesfractions 21 à 30 sont réunies puis concentrées dans les conditions de ci-dessus. Onobtient 0,84 g de (3 R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propylj-1-(2-(2-thiénylthio)éthyljpipéridine-3-acétate de méthyle, sous forme d’une huile jaune pâle.Spectrum of R.M.N. ^ H (400 MHz, (CD3) 2SO d6 at a temperature of 383K, δ enppm). A mixture of two diastereoisomers is observed: from 1.40 to 2.00 and from 2.25 to 2.70 (mts: 10H in total); from 2.90 to 3.40 (mf: 4H); 3.27 (mt: 4H); 3.61 and 3.63 (2s: 3H in total); 4.00 (s: 3H); 5.38 (mt: 1H); 7.10 (dd, J = 5 and 3.5 Hz: 1H); 7.29 (broad d, J = 3.5 Hz: 1H); from 7.55 to 7.60 (mt: 2H); 7.65 (d, J = 5 Hz: 1H; 7.76 (mt: 1H); 8.16 (d, J = 9.5 Hz: 1H); 8.85 (d, J - 4.5); Hz: 1H) 120 22 248 (3R, 4R) -4- [3-Oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (2- (2-thienylthio) ethyl] piperidine-3 Methyl acetate To a solution of 2.8 g of methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate in 60 cc d acetonitrile 1.5 g of 2- (2-chloroethylthio) thiophene and then 5.2 g of potassium carbonate and 2.5 g of potassium iodide are added at a temperature in the region of 20 ° C. with stirring. The mixture is heated for 20 hours at a temperature close to reflux and then cooled to about 20 ° C. 130 cm 3 of water and 50 cm 3 of ethyl acetate are added to the reaction mixture. After decantation of the mixture, the organic phase is washed with 150 cm3 of water, dried over magnesium sulphate, filtered and then concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. An oil is obtained which is purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45μ; diameter 2.5 cm; silicel00 cm3 volume) eluting with a mixture of dichloromethane-methanol (95/5 by volume). First, a fraction of 30 cm 3 is collected, followed by fractions of approximately 10 cm 3. The fractions 1 to 4 sontréunies, then evaporated as before. 2.3 g of a brown oil are obtained and subjected a second time to purification by atmospheric pressure chromatography on a column of silica gel (particle size 20-45 μ, diameter 2.5 cm, silica volume 300 cm 3), eluting with a mixture of dichloromethane-methanol (99/1 by volume) and collecting fractions of about 10 cm3. Fractions 21 to 30 are combined and then concentrated under the conditions of above. 0.84 g of methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (2- (2-thienylthio) ethyl] piperidine-3-acetate are obtained in the form of a pale yellow oil.

Spectre infra rouge (CH2C12) : 2937 ; 2806 ; 2765 ; 1731 ; 1693 ; 1620 ; 1505 ; 1243et 849 cm'1 (3R,4R)-4-[3-Oxo-3-(6-méthoxyquinoiin-4-yl)propyl]pipéridine-3-acétate deméthyleInfra red spectrum (CH2Cl2): 2937; 2806; 2765; 1731; 1693; 1620; 1505; 1243 and 849 cm -1 (3 R, 4 R) -4- [3-Oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-methyl acetate

Une solution de 10,8 g d’acide (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]-l-(tert-butyloxycarbonyl)pipéridine-3-acétique dans 460 cm3 de méthanol anhydreadditionnés de 4,3 cm3 d’acide sulfurique concentré (d=l,83) est chauffée à unetempérature voisine de 65 °C sous agitation pendant 2 heures. Après refroidissementaux environs de 20°C, le mélange réactionnel est évaporé sous pression réduite(5 kPa) à une température voisine de 40°C, puis le résidu obtenu est repris par 120 2 2 249 200 cm3 d’eau, rendu alcalin par addition d’hydrogénocarbonate de sodium jusqu'àl’obtention d’un pH voisin de 8-9. Le mélange est extrait par 4 fois 200 cm3 d’acétated’éthyle. La phase aqueuse est alcalinisée jusqu'à un pH voisin de 11 par addition dela quantité nécessaire dé carbonate de sodium. Le mélange est extrait par 2 fois200 cm3 d’acétate d’éthyle. Les extraits organiques sont réunis, séchés sur sulfate demagnésium, filtrés, évaporés sous pression réduite (5 kPa) à une température voisinede 40°C. On obtient 6,84 g de (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]pipéridiné-3-acétate de méthyle, sous forme d’une huile de couleur brune.A solution of 10.8 g of (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) piperidine-3-acetic acid in 460 cm3 of anhydrous methanol containing 4.3 cm3 of concentrated sulfuric acid (d = 1.83) is heated to a temperature of 65 ° C. with stirring for 2 hours. After cooling to about 20 ° C., the reaction mixture is evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C., and the residue obtained is taken up in 120.2 cm 2 of water, made alkaline by addition. sodium hydrogen carbonate until a pH of 8-9 is reached. The mixture is extracted with 4 times 200 cm3 of ethyl acetate. The aqueous phase is alkalinized to a pH of about 11 by adding the necessary amount of sodium carbonate. The mixture is extracted with 2 times 200 cm3 of ethyl acetate. The organic extracts are combined, dried over magnesium sulphate, filtered and evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 6.84 g of methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidin-3-acetate are obtained in the form of a brown oil. .

Spectre infra rouge (CC14) : 2935 ; 2812 ; 1738 ; 1692 ; 1620 ; 1504 ; 1242 ; 1032 et851 cm*’Infrared spectrum (CCl4): 2935; 2812; 1738; 1692; 1620; 1504; 1242; 1032 and 851 cm * '

Acide (3R,4R)-4-[3-oxo-3-(6-méthoxyqumolin-4-yI)propyI]-l-(Zerp- butyloxycarbonyl)pipéridine-3-acétique A une solution de 1,2 g de (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]-l-(tert-butyIoxycarbonyl)pipéridine-3-acétaldéhyde dans 60 cm3 d’acétone, on ajoute en1 heure environ, sous agitation et à une température voisine de 25°C, une solution de0,85 g de permanganate de potassium dans 25 cm3 d’eau et 120 cm3 d’acétone. Lemélange est agité pendant 3 heures à cette même température, puis refroidi à environ10°C. Une solution de 5 g de sulfite de sodium dans 200 cm3 d’eau est ajoutée aumélange réactionnel, puis le mélange obtenu est filtré sur célite. L’acétone du filtratest évaporée sors pression réduite (5 kPa) à une température voisine de 40°C, puis lerésidu d’évaporation est «épris par 200 cm3 d’eau, lavé par 200 cm3 d’étherdiéthylique. La phase aqueuse est décantée, acidifiée par de l’acide citrique à l’étatsolide à un pH voisin de 3-4, extraite par 200 cm3 d’éther diéthylique. La solutionéthérée décantée est séchée sur sulfate de magnésium, filtrée, évaporée dans lesconditions de ci-dessus. On obtient 0,74 g d’acide (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(/err-butyloxycarbonyl)pipéridine-3-acétique, sousforme d’un solide jaune.(3R, 4R) -4- [3-Oxo-3- (6-methoxy-iminolin-4-yl) propyl] -1- (2-piperyloxycarbonyl) piperidine-3-acetic acid To a solution of 1.2 g of ( 3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) piperidine-3-acetaldehyde in 60 cm3 of acetone is added in about 1 hour. with stirring and at a temperature in the region of 25 ° C., a solution of 0.85 g of potassium permanganate in 25 cm 3 of water and 120 cm 3 of acetone. The mixture is stirred for 3 hours at the same temperature and then cooled to about 10 ° C. A solution of 5 g of sodium sulphite in 200 cm3 of water is added to the reaction mixture, and the mixture obtained is filtered on celite. The acetone of the filtrate is evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C., then the evaporation residue is "scented with 200 cm 3 of water and washed with 200 cm 3 of diethyl ether. The aqueous phase is decanted, acidified with citric acid to the statesolid at a pH of about 3-4, extracted with 200 cm3 of diethyl ether. The decanted ether solution is dried over magnesium sulfate, filtered and evaporated in the above conditions. 0.74 g of (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (1-butyloxycarbonyl) piperidine-3-acetic acid are obtained, in the form of a yellow solid.

Spectre infra rouge (KBr) : 2932 ; 2588 ; 1730 ; 1690 ; 1620 ; 1431 ; 1246 ; 1165 et857 cm'' (3R,4R)-4-[3-Oxo-3-(6-méthoxyquinolin-4-yI)propyl]-l-(Ze/T- butyloxycarbonyi)pipérïdine-3-acétaIdéhyde 250 120 2 2 A une solution de 8,3 cm3 de chlorure d’oxalyle dans 65 cm3 de dichlorométhanerefroidie à une température voisine de -60°C, on ajoute lentement, sous agitation etsous atmosphère inerte, un mélange de 13,7 g de diméthylsulfoxyde dans 65 cm3 dedichlorométhane. Après 15 minutes d’agitation du mélange, on ajoute lentement 10 gde (3R,4R)-3-(2-hydroxyéthyl)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-(ieri-butyloxycarbonyl)pipéridine solubilisés dans 65 cm3 de dichloro-méthane. Après 30 minutes d’agitation du mélange, on ajoute finalement, goutte àgoutte, 61,7 cm3 de triéthylamine dissous dans 65 cm3 de dichlorométhane. Lemélange est encore agité pendant 3 heures aux environs de -60°C, puis versé sur400 cm3 d’eau glacée. Après décantation du mélange, la phase organique est lavée par400 cm3 d’une solution aqueuse d’acide citrique à 10 % (en masse), puis séchée sursulfate de magnésium, filtrée, évaporée sous pression réduite (5 kPa) à unetempérature voisine de 40°C. On obtient 9,95 g de (3R,4R)-4-[3-oxo-3-(6-méthoxy-quinolin-4-yl)propyl]-1 -(/er/-butyloxycarbonyl)pipéridine-3-acétaldéhyde, sous formed’une huile de couleur brune.Infra red spectrum (KBr): 2932; 2588; 1730; 1690; 1620; 1431; 1246; 1165 and 857 cm -1 (3R, 4R) -4- [3-Oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (N, N-butyloxycarbonyl) piperidin-3-acetaldehyde 250 120 2 2 To a solution of 8.3 cm3 of oxalyl chloride in 65 cm3 of dichloromethane-cooled at a temperature in the region of -60 ° C, a mixture of 13.7 g of dimethylsulfoxide in 65 cm3 is slowly added under stirring and under an inert atmosphere. dedichlorométhane. After stirring for 15 minutes, 10 g of (3R, 4R) -3- (2-hydroxyethyl) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-) yl) propyl] -1- (ieri-butyloxycarbonyl) piperidine solubilized in 65 cm3 of dichloromethane. After stirring for 30 minutes, 61.7 cm3 of triethylamine dissolved in 65 cm3 of dichloromethane are finally added dropwise. Lemélange is stirred for 3 hours at about -60 ° C and poured over 400 cm3 of ice water. After decantation of the mixture, the organic phase is washed with 400 cm 3 of a 10% aqueous citric acid solution (by weight), then dried over magnesium sulphate, filtered and evaporated under reduced pressure (5 kPa) at a temperature in the region of 40.degree. ° C. 9.95 g of (3R, 4R) -4- [3-oxo-3- (6-methoxy-quinolin-4-yl) propyl] -1 - (/ er-butyloxycarbonyl) piperidine-3-acetaldehyde are obtained. in the form of a brown oil.

Spectre infra rouge (CC14) : 2932 ; 2720 ; 1729 ; 1694 ; 1430 ; 1244 ; 1164 et 850 cm’1 (3R,4R)-3-(2-HydroxyéthyI)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4- yl)propyl]-l-(ter/-butyloxycarbonyl)pipéridine A une solution de 52,6 g de (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]-l-(ieri-butyloxycarbonyl)-3-vinylpipéridine dans 500 cm3 de toluène, on ajoute 33,4cm3 de complexe de triéthylamine borane sous agitation, à une température voisine de20°C, puis le mélange est chauffé pendant 18 heures à une température voisine de110°C. Après avoir concentré le mélange réactionnel sous pression réduite (5 kPa) àune température voisine de 45°C, le résidu obtenu est repris par 500 cm3 detétrahydrofùranne. La solution qui en résulte est additionnée en 20 minutes environ de63 cm3 d’eau, puis on ajoute en 1 heure environ et par petites fractions, 47,5 g deperborate de sodium. Le mélange est agité pendant 4 heures à une température voisinede 20°C, puis on ajoute 300 cm3 d’une solution saturée de chlorure d’ammonium. Lasolution organique est décantée, séchée sur sulfate de magnésium, concentrée dans lesmêmes conditions que ci-dessus. Le résidu obtenu est purifié par chromatographie surune colonne de gel de silice (granulométrie 20-45μ ; diamètre 9 cm ; volume silice2500 cm3) en éluant d’abord par un mélange de dichlorométhane-méthanol (97,5/2,5en volumes) et en recueillant des fractions d’1 litre. Les fractions 1 à 17 sont séparées,puis on élue par un mélange de dichlorométhane-méthanol (95/5 en volumes) en 12022 251 recueillant des fractions d’I litre. Les fractions 30 à 35 sont réunies et l’on éluefinalement par un mélange de dichlorométhane-méthanol (90/10 en volumes) enrecueillant des fractions d’I litre. Les fractions 36 à 41 sont réunies, tandis quel’ensemble des fractions 30 à 41 est évaporé sous pression réduite (5 kPa) à unetempérature voisine de 40°C. On obtient 20 g de (3R,4R)-3-(2-hydroxyéthyl)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoIin-4-yI)propylj-1 -(tert- butyloxycarbonyl)pipéridine, sous forme d’une huile.Infrared spectrum (CCl4): 2932; 2720; 1729; 1694; 1430; 1244; 1164 and 850 cm -1 (3R, 4R) -3- (2-hydroxyethyl) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- ( tert-Butyloxycarbonyl) piperidine To a solution of (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (ieri-butyloxycarbonyl), 52.6 g 3-vinylpiperidine in 500 cm3 of toluene is added 33.4 cm3 of triethylamine borane complex stirring at a temperature of 20 ° C, then the mixture is heated for 18 hours at a temperature of 110 ° C. After concentrating the reaction mixture under reduced pressure (5 kPa) at a temperature in the region of 45 ° C., the residue obtained is taken up in 500 cm 3 of tetrahydrofuran. The resulting solution is added in about 20 minutes of 63 cm3 of water, then 47.5 g of sodium perperate are added in about 1 hour and in small portions. The mixture is stirred for 4 hours at a temperature in the region of 20 ° C., then 300 cm 3 of a saturated solution of ammonium chloride are added. The organic solution is decanted, dried over magnesium sulfate, concentrated under the same conditions as above. The residue obtained is purified by chromatography on a column of silica gel (particle size 20-45 μ, diameter 9 cm, silica volume 2500 cm 3), eluting firstly with a mixture of dichloromethane-methanol (97.5 / 2.5 volumes) and by collecting fractions of 1 liter. Fractions 1 to 17 are separated and then eluted with a mixture of dichloromethane-methanol (95/5 by volume), collecting 1 liter fractions. Fractions 30 to 35 are combined and finally eluted with a mixture of dichloromethane-methanol (90/10 by volume) containing 1 liter fractions. Fractions 36 to 41 are combined, while all fractions 30 to 41 are evaporated under reduced pressure (5 kPa) at a temperature of 40 ° C. 20 g of (3R, 4R) -3- (2-hydroxyethyl) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (tert.p. butyloxycarbonyl) piperidine, in the form of an oil.

Spectre infrarouge (CH2C12) : 3612 ;2480 ;2937 ;1680 ;1432 ;1243 ;1163 et 859 cm*1 (3R,4R)-4-[3-Oxo-3-(6-méthoxyquinolin-4-yl)propyl]-l-(r^rt-butyloxycarbonyl)- 3- vinylpipéridine A une solution agitée de 126 g de (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]-3-vinylpipéridine dans 1700 cm3 de dichlorométhane, on ajoute en 20 minutesenviron, à une température voisiné de 20°C, 162 cm3 de triéthylamine, puis en 2heures 85 g de di-tertiobutyl dicarbonate solubilisés dans 300 cm3 dedichlorométhane. Le mélange est agité pendant 16 heures à une température voisinede 20°C, puis on y ajoute 400 cm3 d’eau. La phase organique est décantée, séchée sursulfate de magnésium, filtrée, évaporée sous pression réduite (5 kPa) à unetempérature voisine de 40°C. On obtient un résidu huileux que l’on reprend par1000 cm3 d’acétate d’éthyle et que l’on lave par .2 fois 200 cm’d’eau, 1 fois par250 cm3d.’une solution aqueuse saturée d’acide citrique, 2 fois par 200 cm3 d’eau. Lasolution organique est séchée sur sulfate de magnésium, filtrée, concentrée dans lesconditions de ci-dessus. On obtient 148 g de (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin- 4- yl)propyl]-l-(/err-butyloxycarbonyl)-3-vinylpipéridine, sous forme d’une huile decouleur brune.Infrared spectrum (CH 2 Cl 2): 3612, 2480, 2937, 1680, 1432, 1243, 1163 and 859 cm -1 (3R, 4R) -4- [3-Oxo-3- (6-methoxyquinolin-4-yl) propyl] 1- (trans-butyloxycarbonyl) -3-vinylpiperidine To a stirred solution of 126 g of (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -3 -vinylpiperidine in 1700 cm3 of dichloromethane is added in about 20 minutes, at a temperature of 20 ° C, 162 cm3 of triethylamine, then in 2 hours 85 g of di-tert-butyl dicarbonate solubilized in 300 cm3 of dichloromethane. The mixture is stirred for 16 hours at a temperature in the region of 20 ° C. and then 400 cm3 of water are added thereto. The organic phase is decanted, dried over magnesium sulphate, filtered, evaporated under reduced pressure (5 kPa) at a temperature of 40 ° C. An oily residue is obtained, which is taken up in 1000 cm 3 of ethyl acetate and which is washed twice with 200 cm 3 of water and once with 250 cm 3 of a saturated aqueous solution of citric acid. 2 times per 200 cm3 of water. The organic solution is dried over magnesium sulfate, filtered, concentrated in the conditions of above. 148 g of (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (1-butyloxycarbonyl) -3-vinylpiperidine are obtained in the form of a brownish oil.

Spectre infrarouge (CH2C12) : 2979 ;1683 ; 1431 ;1246 ;1164 et 853 cm'1IR spectrum (CH 2 Cl 2): 2979, 1683; 1431, 1246, 1164 and 853 cm -1

La (3R,4R)-4-[3-oxo-3-(6-méthoxyquinoIin-4-yl)propyl]-3-vinylpipéridine peut êtreobtenue par application de la méthode décrite dans la demande de brevetFR2 354 771.(3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -3-vinylpiperidine can be obtained by application of the method described in patent application FR 2 354 771.

Exemple 49Example 49

Acide (3R,4R)-l-[2-(3-fluorophénylthio)éthyl]-4-[3-hydroxy-3-(6-méthoxy-quinolin-4-yi)propylJpipéridine-3-acétique, diastéréoisomère A et acide (3R,4R)- 252 l-(2-(3-fluorophénylthio)éthyIJ-4-[3-hydroxy-3-(6-méthoxyquinolin-4-yI)propyI]pipéridine-3-acétique, diastéréoisomère B.(3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3-hydroxy-3- (6-methoxy-quinolin-4-yl) propyl] piperidine-3-acetic acid, diastereoisomer A and acid (3R, 4R) -25- [1- (2- (3-fluorophenylthio) ethyl] -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetic acid, diastereoisomer B.

On chromatographie 0,7 g d’acide (3R,4R)-l-[2-(3-fluorophénylthio)éthyl]-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-acétique sur unecolonne de 35 cm de long et 6 cm de diamètre, conditionnée avec 700 g de siliceKROMASIL® (granulométrie 10μ). L’élution est effectuée à l’aide d’un mélange dedichlorométhane-acétonitrile-méthanol-triéthylamine (56/40/4/0,5 en volumes). Ledébit est de 70 cm3/mn. La détection est effectuée en ultra violet à 265 nm. Plusieursinjections préparatives ont conduit à la séparation des 2 diastéréoisomères. Lesfractions correspondant au premier, le diastéréoisomère A, sont concentrées souspression réduite (5 kPa) à une température voisine de 40°C. La masse cristallineobtenue est séchée à l’étuve sous pression réduite (10 Pa) à une température voisinede 20°C. On obtient 0,185 g d’acide (3R,4R)-l-[2-(3-fluorophénylthio)éthyl]-4-[3-hydroxy-3 - (6 · méthoxy quino lin-4-y l)propy ljpipéridi ne-3 -acétique, diastéréoisomère A, sous forme d’un solide de couleur blanc cassé. (ocD20 = -55,9 +/-1,2 dans leméthanol à 0,5 %). Les fractions mélange sont concentrées dans les mêmes conditionsque ci-dessus pour retraitement. De nouvelles injections sont réalisées pour obtenir lesecond diastéréoisomère. Trois injections préparatives permettent d’obtenir lesfractions correspondant au diastéréoisomère B. Celles-ci sont concentrées souspression réduite (5 kPa) à une température voisine de 40°C. La masse cristallineobtenue est séchée à l’étuve sous pression réduite (10 Pa) à une température voisinede 20°C. On obtient 0,200 g d’acide(3R,4R)-l-[2-(3-fluorophénylthio)éthyl]-4-[3-hydroxy-3-(6-méthoxy-quinolin-4-yl)propyl]pipéridine-3-acétique, diastéréoisomère B, sous forme d’un solide de couleur blanc cassé. (aD20 = +41,0 +/-1,0 dans leméthanol à 0,5 %). diastéréoisomère A : Spectre de R.M.N.^H (400 MHz, (CD3)2SO d6, δ en ppm) : de 1,15 à 1,85 et de 1,95 à 2,20 (2 séries de mts : 11H en totalité) ; de 2,40 à 2,60 (mt :3H) ; 2,65 à 2,80 (mt : 2H) ; 3,08 (t, J = 7 Hz : 2H) ; 3,92 (s : 3H) ; 5,27 (mt : 1H) ; 5,52 (mf : 1H) ; 6,98 (t dédoublé, J = 8,5 et 2,5 Hz : 1H) ; de 7,10 à 7,20 (mt : 2H) ;de 7,25 à 7,45 (mt : 3H) ; 7,55 (d, J = 4,5 Hz : 1H) ; 7,94 (d, J = 9 Hz : 1H) ; 8,71 (d, J= 4,5 Hz : 1H). diastéréoisomère B : Spectre de R.M.NJH (400 MHz, (CD3)2SO d6, δ en ppm) : de1,30 à 1,90 et de 1,95 à 2,15 (2 séries de mts : 10H en totalité) ; de 2,40 à 2,60 (mt :3H) ; 2,75 (mt : 1H) ; de 2,95 à 3,15 (mf : 2H) ; 3,10 (t, J = 7 Hz : 2H) ; 3,93 (s : 3H) ; 253 120 2 2 5,28 (mt : 1H) ; 5,53 (d, J = 5 Hz : 1H) ; 7,00 (t dédoublé, J = 8,5 et 2,5 Hz : 1 H) ; de 7,10 à 7,20 (mt : 2H) ; 7,35 (mt : 1H) ; de 7,35 à 7,45 (mt : 2H) ; 7,55 (d, J = 4,5 Hz :1H) ; 7,95 (d, J = 9,5 Hz : 1H) ; 8,72 (d, J = 4,5 Hz : 1H) ; de 11,00 à 12,5 (mf trèsétalé : 1H).0.7 g of (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4- yl) propyl] piperidine-3-acetic acid on a column 35 cm long and 6 cm in diameter, conditioned with 700 g of silica KROMASIL® (particle size 10μ). The elution is carried out using a mixture of dichloromethane-acetonitrile-methanol-triethylamine (56/40/4 / 0.5 by volume). Ledebit is 70 cm3 / min. The detection is carried out in ultraviolet at 265 nm. Several preparative injections led to the separation of the two diastereoisomers. Fractions corresponding to the first, diastereoisomer A, are concentrated under reduced pressure (5 kPa) at a temperature of 40 ° C. The crystalline mass obtained is dried in an oven under reduced pressure (10 Pa) at a temperature in the region of 20 ° C. 0.185 g of (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3-hydroxy-3 - (6-methoxyquinolin-4-yl) propyl] piperidine are obtained. 3-Acetic acid, diastereoisomer A, in the form of an off-white solid. (ocD20 = -55.9 +/- 1.2 in 0.5% ethanol). The mixing fractions are concentrated under the same conditions as above for reprocessing. New injections are made to obtain the second diastereoisomer. Three preparative injections make it possible to obtain the fractions corresponding to diastereoisomer B. These are concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. The crystalline mass obtained is dried in an oven under reduced pressure (10 Pa) at a temperature in the region of 20 ° C. 0.200 g of (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3-hydroxy-3- (6-methoxy-quinolin-4-yl) propyl] piperidine- 3-acetic acid, diastereoisomer B, in the form of an off-white solid. (aD20 = +41.0 +/- 1.0 in 0.5% ethanol). diastereoisomer A: 1 H NMR spectrum (400 MHz, (CD3) 2SO d6, δ in ppm): from 1.15 to 1.85 and from 1.95 to 2.20 (2 series of mts: 11H in total) ; from 2.40 to 2.60 (mt: 3H); 2.65 to 2.80 (mt: 2H); 3.08 (t, J = 7 Hz: 2H); 3.92 (s: 3H); 5.27 (mt: 1H); 5.52 (mf: 1H); 6.98 (t split, J = 8.5 and 2.5 Hz: 1H); from 7.10 to 7.20 (mt: 2H), from 7.25 to 7.45 (mt: 3H); 7.55 (d, J = 4.5 Hz: 1H); 7.94 (d, J = 9 Hz: 1H); 8.71 (d, J = 4.5 Hz: 1H). diastereoisomer B: Spectrum of R.M.NJH (400 MHz, (CD3) 2SO d6, δ in ppm): from 1.30 to 1.90 and from 1.95 to 2.15 (2 series of mts: 10H in total); from 2.40 to 2.60 (mt: 3H); 2.75 (mt: 1H); 2.95 to 3.15 (mf: 2H); 3.10 (t, J = 7 Hz: 2H); 3.93 (s: 3H); 253 120 2 5.28 (mt: 1H); 5.53 (d, J = 5 Hz: 1H); 7.00 (t split, J = 8.5 and 2.5 Hz: 1H); from 7.10 to 7.20 (mt: 2H); 7.35 (mt: 1H); from 7.35 to 7.45 (mt: 2H); 7.55 (d, J = 4.5 Hz: 1H); 7.95 (d, J = 9.5 Hz: 1H); 8.72 (d, J = 4.5 Hz: 1H); from 11.00 to 12.5 (half-melted: 1H).

Acide (3R,4R)-l-(2-(3-fluorophényithio)éthyl]-4-[3-(R,S)-hydroxy-3-(6- méthoxyquinolin-4-yl)propyl] pipéridine-3-acétique(3R, 4R) -1- (2- (3-Fluorophenylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3- acid acetic

Une solution de 1,3 g de (3R,4R)-l-[2-(3-fluorophénylthio)éthyl]-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-acétate de méthyle dans20 cm3 de dioxanne, additionnée de 2 cm3 de soude aqueuse 5N, est chauffée sousagitation pendant 20 heures à une température voisine de 60°C. Le mélangeréactionnel est évaporé sous pression réduite (5 kPa) à une température voisine de40°C, puis le résidu obtenu est repris par 30 cm3 d’eau et 5 cm3 de inéthanol, acidifiépar de l’acide citrique. Les solvants sont évaporés dans les mêmes conditions queprécédemment, puis le résidu obtenu est repris par 70 cm3 d’un mélange dedichlorométhane-méthanol (80/20 en volumes). Les cristaux d’acide citrique sontfiltrés ; le filtrat est évaporé comme ci-dessus, et le résidu d’évaporation est repris par30 cm’d’éther diéthylique, filtré, séché à l’air. On obtient 1,1g d’acide (3R,4R)-l-[2-(3-fluorophénylthio)éthyl]-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4- yI)propyl]pipéridine-3-acétique, sous forme d’un solide de couleur crème.A solution of (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl), 1.3 g ) propyl] piperidine-3-methyl acetate in 20 cm3 of dioxane, supplemented with 2 cm3 of 5N aqueous sodium hydroxide, is heated under stirring for 20 hours at a temperature of 60 ° C. The reaction mixture is evaporated under reduced pressure (5 kPa) at a temperature of 40 ° C, then the residue obtained is taken up in 30 cm3 of water and 5 cm3 of ethanol, acidified with citric acid. The solvents are evaporated under the same conditions as above, then the residue obtained is taken up in 70 cm3 of a mixture of dichloromethane-methanol (80/20 by volume). The citric acid crystals are filtered; the filtrate is evaporated as above, and the evaporation residue is taken up in 30 cm 3 of diethyl ether, filtered and dried in air. 1.1 g of (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) acid are obtained. ) propyl] piperidine-3-acetic acid as a cream-colored solid.

Spectre de R.M.N. (300 MHz, (CD3)2SO dé, δ en ppm). On observe un mélangede deux diastéréoisomères : de 1,15 à 1,90 - de 2,00 à 2,25 et de 2,35 à 2,90 (mts : 16H en totalité) ; 3,13 (t large,J = 7 Hz : 2H) ; 3,92 (s : 3H) ; 5,27 (mt : 1H) ; 5,54 (mt : 1H) ; 7,00 (t dédoublé, J = 8,5 Hz : 1H) ; de 7,10 à 7,25 (mt : 2H) ; de 7,30 à 7,50 (mt : 3H) ; 7,55 (mt : 1H) ;7,94 (d, J = 9 Hz : 1H) ; 8,71 (d, J - 4,5 Hz : 1H) ; de 11,50 à 13,50 (mf très étalé :1H).Spectrum of R.M.N. (300 MHz, (CD3) 2SO dec, δ in ppm). There is a mixture of two diastereoisomers: from 1.15 to 1.90 - from 2.00 to 2.25 and from 2.35 to 2.90 (mts: 16H in all); 3.13 (broad t, J = 7 Hz: 2H); 3.92 (s: 3H); 5.27 (mt: 1H); 5.54 (mt: 1H); 7.00 (t split, J = 8.5 Hz: 1H); from 7.10 to 7.25 (mt: 2H); from 7.30 to 7.50 (mt: 3H); 7.55 (mt: 1H); 7.94 (d, J = 9 Hz: 1H); 8.71 (d, J - 4.5 Hz: 1H); from 11.50 to 13.50 (mf very spread: 1H).

Exemple 49AExample 49A

Dichlorhydrate de (3R,4R)-l-[2-(3-fluorophénylthio)éthyI]-4-{3-(R;S)-hydroxy-3-(6-méthoxyquinoIin-4-yI)propyl]pipéridine-3-acétate de méthyle A une solution de 3,2 g de (3R,4R)-l-[2-(3-fluorophényIthio)éthyl]-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-acétate de méthyle dans 50 cm3 de 120 2 2 254 méthanol, additionnée de 2 gouttes de soude aqueuse 5N et maintenue à unetempérature voisine de 20°C, on ajoute sous agitation et par petites fractions 0,28 g deborohydrure de sodium. Le mélange est agité pendant 4 heures à une températurevoisine de 20°C. Après addition de 30 cm3 d’eau, le mélange est extrait par 2 fois30 cm3 de dichlorométhane. Les phases organiques réunies sont lavées par 60 cm3d’eau, séchées sur sulfate de magnésium, filtrées, évaporées sous pression réduite(5 kPa) à une température voisine de 40°C. L’huile résiduelle est purifiée parchromatographie à pression atmosphérique sur une colonne de gel de silice(granulométrie 20-45μ ; diamètre 4 cm ; volume silice 520 cm3), en éluant par unmélange de dichlorométhane-méthanol (99/1) et en recueillant des fractions d’environ60 cm3. Les fractions 40 à 72 sont réunies puis évaporées comme dans les conditionsprécédentes. On obtient 1,7 g d’une huile dont on fait le chlorhydrate de la façonsuivante : une solution de 0,30 g d’huile dans 5 cm3 d’éther diéthylique est versée sur5 cm3 d’éther chlorhydrique 5N. Le gel obtenu est dilué par 10 cm3 d’éther, agitépendant 15 minutes à une température voisine de 20°C, puis évaporé sous pressionréduite (5 kPa) à une température voisine de 30°C. Le résidu obtenu est solubilisédans 30 cm3 d’eau, puis lyophilisé. On obtient 0,26 g de dichlorhydrate de (3R,4R)-1-[2-(3-fiuorophénylthio)éthyl]-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-acétate de méthyle, sous forme d’un lyophilisât de couleur crème.(3R, 4R) -1- [2- (3-Fluorophenylthio) ethyl] -4- {3- (R; S) -hydroxy-3- (6-methoxyquinyl-4-yl) propyl] piperidine-3-dihydrochloride Methyl acetate To a solution of 3.2 g of (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-methyl acetate in 50 cm3 of methanol, added with 2 drops of 5N aqueous sodium hydroxide and maintained at a temperature in the region of 20 ° C., 0.28 g of boron hydride are added with stirring and in small portions. sodium. The mixture is stirred for 4 hours at a temperature of 20 ° C. After addition of 30 cm3 of water, the mixture is extracted with twice 30 cm3 of dichloromethane. The combined organic phases are washed with 60 cm3 of water, dried over magnesium sulphate, filtered and evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. The residual oil is purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45 μ, diameter 4 cm, silica volume 520 cm 3), eluting with a mixture of dichloromethane-methanol (99/1) and collecting fractions of about 60 cm3. Fractions 40 to 72 are combined and then evaporated as in the preceding conditions. 1.7 g of an oil of which the hydrochloride is made as follows: a solution of 0.30 g of oil in 5 cm3 of diethyl ether is poured over 5 cm3 of 5N hydrochloric ether. The gel obtained is diluted with 10 cm3 of ether, stirred for 15 minutes at a temperature in the region of 20 ° C, and then evaporated under reduced pressure (5 kPa) at a temperature in the region of 30 ° C. The residue obtained is solubilized in 30 cm3 of water and then freeze-dried. 0.26 g of (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-) dihydrochloride are obtained. yl) propyl] piperidine-3-methyl acetate, in the form of a cream-colored freeze-dried product.

Spectre de R.M.N. (400 MHz, (CD3)2SO d6 avec ajout de quelques gouttes deCD3COOD d4 à une température de 373K, S en ppm). On observe un mélange dedeux diastéréoisomères : de 1,45 à 2,00 et de 2,25 à 2,60 (mts : 10H en totalité) ; de 3,05 à 3,45 (mts : 8H) ;3,60 et 3,63 (2s : 3H en totalité) ; 3,97 et 3,98 (2s : 3H en totalité) ; 5,39 (mt : 1H) ;7,03 (mt : 1H) ; 7,23 (mt : 2H) ; 7,37 (mt : 1H) ; de 7,50 à 7,65 (mt : 2H) ; 7,80 (mt :1H) ; 8,12 (d, J = 9,5 Hz : 1H) ; 8,84 (d, J = 5 Hz : 1H). (3R,4R)-l-[2-(3-FluorophényIthio)éthyl]-4-[3-oxo-3-(6-méthoxyquinolin-4-yI)propyl]pipéridine-3-acétate de méthyle A une solution de 4 g de l-[(2-chloroéthyl)thio]-3-fluorobenzène dans 50 cm3d’acétonitrile, on ajoute goutte à goutta, sous agitation et à une température voisine de20°C, 2,26 g de (3R,4R)-4-[3-oxor3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-acétate de méthyle préalablement solubilisés dans 50 cm3 d’acétonitrile, puis 6,91 gde carbonate de potassium et 2 g cPiodure de potassium. Le mélange est chauffé 120 2 2 255 pendant 18 heures à une température voisine de 70°C. Après une additionsupplémentaire de 0,3 g d’iodure de potassium et un chauffage complémentaire à unetempérature voisine de 70°C pendant 4 heures, la masse réactionnelle est refroidie auxenvirons de 20°C, additionnée de 200 cm3 d’eau, extraite par 2 fois 150 cm3 d’acétated’éthyle. Les extraits réunis sont lavés par 300 cm3 d’eau, séchés sur sulfate demagnésium, filtrés, évaporés sous pression réduite (5 kPa) à une température voisinede 40°C. Le résidu obtenu est purifié par chromatographie à pression atmosphériquesur une colonne de gel de silice (granulométrie 20-45μ ; diamètre 5,2 cm ; volumesilice 950 cm3) en éluant par un mélange de dichlorométhane-méthanol (99/1 envolumes), et en recueillant des fractions d’environ 60 cm3. Les fractions 24 à 36 sontréunies, concentrées dans les conditions de ci-dessus. On obtient 3,3 g de (3R,4R)-1-[2-(3-fluorophénylthio)éthyl]-4~[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-acétate de méthyle, sous forme d’une huile de couleur jaune.Spectrum of R.M.N. (400 MHz, (CD3) 2SO d6 with addition of a few drops ofCD3COOD d4 at a temperature of 373K, S in ppm). A mixture of two diastereoisomers is observed: from 1.45 to 2.00 and from 2.25 to 2.60 (mts: 10H in total); 3.05 to 3.45 (mts: 8H), 3.60 and 3.63 (2s: 3H in all); 3.97 and 3.98 (2s: 3H in total); 5.39 (mt: 1H), 7.03 (mt: 1H); 7.23 (mt: 2H); 7.37 (mt: 1H); from 7.50 to 7.65 (mt: 2H); 7.80 (mt: 1H); 8.12 (d, J = 9.5 Hz: 1H); 8.84 (d, J = 5 Hz: 1H). (3R, 4R) -1- [2- (3-Fluorophenylthio) ethyl] -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-methyl acetate to a solution of 4 g of 1 - [(2-chloroethyl) thio] -3-fluorobenzene in 50 cm3 of acetonitrile is added dropwise, with stirring and at a temperature of 20 ° C, 2.26 g of (3R, 4R) Methyl 4- [3-oxor3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate, previously solubilized in 50 cm3 of acetonitrile, followed by 6.91 g of potassium carbonate and 2 g of potassium iodide. The mixture is heated for 18 hours at a temperature in the region of 70 ° C. After an additional addition of 0.3 g of potassium iodide and additional heating at a temperature in the region of 70 ° C. for 4 hours, the reaction mass is cooled to about 20 ° C., 200 cm.sup.3 of water, extracted with 2 150 cc of ethyl acetate. The combined extracts are washed with 300 cm3 of water, dried over magnesium sulphate, filtered and evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. The residue obtained is purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45μ, diameter 5.2 cm, volumesilice 950 cm 3), eluting with a mixture of dichloromethane-methanol (99/1 volumes), and collecting fractions of about 60 cm3. The fractions 24 to 36 sontréunies, concentrated under the conditions of above. 3.3 g of (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3 are obtained. methyl acetate as a yellow oil.

Spectre infra rouge (CH2C12) : 2936 ; 2806 ; 1731 ; 1692 ; 1620 ; 1505 ; 1474 ; 1243 ;881 et 853 cm'1Infra red spectrum (CH 2 Cl 2): 2936; 2806; 1731; 1692; 1620; 1505; 1474; 1243; 881 and 853 cm -1

Le (3R,4R)-4-[3 -oxo-3-(6-méthoxyquinoIin-4-yl)propyl]pipéridine-3-acétate de méthyle a été obtenu dans l’exemple 48.Methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinyl-4-yl) propyl] piperidine-3-acetate was obtained in Example 48.

Exemple 50Example 50

Acide (BP^RL^-p-fR.Sj-hydroxy-S-fô-i icihoxyqui«olin-4-yl)propyl]-ï-[3-(3,5-difiuorophényI)prop-2-ynyi]pipcr5dine-3-carboxyliqueAcid (B) β-L-p-β-α-hydroxy-5-yl-yloxy-4-yl) propyl] -3- (3,5-difluorophenyl) prop-2-yl] yl] piperidine -3-carboxylic acid

Un mélange de 0,89 g de (3R,4R)~4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyI]-l-[3-(3,5-difluorophényl)prop-2-ynyl3pipéridine-3-carboxylate de méthyledans 9 cm3 de dioxanne additionnés de 1,41 cm3 de soude aqueuse 5N est agitépendant 18 heures à une température voisine de 60°C. Après refroidissement auxenvirons de 20°C, le mélange réactionnel est évaporé sous pression réduite (5 kPa) àune température voisine de 40°C. Le résidu obtenu est purifié par chromatographie,sous une pression d’azote de 50 kPa, sur une colonne de gel de silice (granulométrie20-45μ ; diamètre 3,3 cm ; masse 56 g) en éluant d’abord par un mélange dedichlorométhane-méthanol (95/5 en volumes). On recueille d’abord une fraction de100 cm3, puis des fractions de 16 cm3. Les fractions 1 à 36 sont séparées. On élueensuite par un mélange de dichlorométhane-méthanol (75/25 en volumes). Oneffectue une première fraction de 200 cm3, une seconde de 150 cm3, puis unetroisième de 100 cm3. Ces deux dernières sont réunies, concentrées comme ci-dessus. 120 2 2 256A mixture of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (3,5-di-) Methyl-difluorophenyl) prop-2-ynylpiperidine-3-carboxylate in 9 cm3 of dioxane supplemented with 1.41 cm3 of 5N aqueous sodium hydroxide is stirred for 18 hours at a temperature in the region of 60 ° C. After cooling to about 20 ° C, the reaction mixture is evaporated under reduced pressure (5 kPa) at a temperature of 40 ° C. The residue obtained is purified by chromatography, under a nitrogen pressure of 50 kPa, on a column of silica gel (particle size 20-45μ, diameter 3.3 cm, mass 56 g), eluting firstly with a dichloromethane / methylene chloride mixture. methanol (95/5 by volume). First a fraction of 100 cm3 is collected, then fractions of 16 cm3. Fractions 1 to 36 are separated. Then eluted with a mixture of dichloromethane-methanol (75/25 by volume). One performs a first fraction of 200 cm3, a second of 150 cm3, then a third of 100 cm3. These last two are united, concentrated as above. 120 2 256

Le résidu obtenu est repris dans le dichlorométhane, filtré. Le filtrat est évaporécomme précédemment, puis le nouveau résidu obtenu est trituré dans 25 cm3 d’unmélange d’éther diisopropylique-pentane (50/50 en volumes). Le produit quicristallise est filtré, lavé par 2 fois 10 cm3 du même mélange, puis 3 fois 10 cm3 de 5 pentane. On obtient 0,53 g d’acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(3,5-difluorophényl)prop-2-ynyl]pipéridine-3-carboxylique, sous forme d’un solide de couleur crème fondant à 106°C.The residue obtained is taken up in dichloromethane, filtered. The filtrate is evaporated as before, and then the new residue obtained is triturated in 25 cm 3 of a mixture of diisopropyl ether-pentane (50/50 by volume). The quicristallized product is filtered, washed with twice 10 cm 3 of the same mixture, then 3 times 10 cm 3 of pentane. 0.53 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3), 5-difluorophenyl) prop-2-ynyl] piperidine-3-carboxylic acid as a cream-colored solid melting at 106 ° C.

Spectre de R.M.N. (300 MHz, (CD3)2SO d6, δ en ppm). On observe un mélangede deux diastéréoisomères : 10 de 1,40 à 1,95 (mt : 7H) ; de 2,30 à 3,00 (mt : 5H) ; 3,57 et 3,59 (2s : 2H en totalité) ;3,90 et 3,93 (2s : 3H en totalité) ; 5,25 (mt : 1H) ; 5,55 (mf : 1H) ; 7,22 (mt : 2H) ; de7,25 à 7,45 (mt : 3H) ; 7,56 (mt : 1H) ; 7,94 (d, J = 9 Hz : 1H) ; 8,70 (d, J = 4,5 Hz :1H) ; de 12,10 à 12,80 (mf étalé : 1H). (3R,4R)-4-[3-(R,S)-Hydroxy-3-(6-méthoxyquinoIin-4-yI)propyl]-l-[3-(3,5- 15 difluorophényl)prop-2-ynyl]pipéridine-3-carboxylate de méthyle A un mélange de 0,95 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-(prop-2-ynyl)pipéridine-3-carboxylate de méthyle dans 9,5 cm3 detriéthylamine, agité à une température voisine de 20°C sous atmosphère inerte, onajoute 0,138 g de tétrakis triphénylphosphine palladium, 0,046 g d’iodure cuivreux et 20 0,42 cm3 de l-bromo-3,5-difluorobenzène. Le mélange est chauffé à une température voisine de 80°C pendant 3 heures. Après refroidissement à environ 20°C, le mélangeréactionnel est repris par 30 cm3 d’acétate d’éthyle et 30 cm3 d’eau, agité pendant5 minutes. La phase organique est décantée tandis que la couche aqueuse est extraitepar 2 fois 30 cm3 d’acétate d’éthyle. Les extraits organiques sont réunis, lavés par 25 3 fois 30 cm3 d’eau, séchés sur sulfate de sodium, filtrés, concentrés sous pression réduite (5 kPa) à une température voisine de 40°C. Le résidu obtenu est purifié parchromatographie sous une pression d’azote de 50 kPa, sur une colonne de gel de silice(granulométrie 20-45μ ; diamètre2,3 cm ; 40 g) en éluant par de l’acétate d’éthyle pur.On recueille d’abord 2 fractions de 100 cm3, puis on effectue des fractions de 20 cm3. 30 Les fractions 8 à 40 sont réunies, évaporées dans les conditions de ci-dessus. Onobtient 0,967 g de (3R,4R)-4-{3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-ÿi)propyl]-l-[3-(3,5-difluorophényl)prop-2-ynyl]pipéridine-3-carboxylate de méthyle, sous formed’une meringue de couleur orangée. x 120 22 257Spectrum of R.M.N. (300 MHz, (CD3) 2SO d6, δ in ppm). A mixture of two diastereoisomers is observed: from 1.40 to 1.95 (mt: 7H); from 2.30 to 3.00 (mt: 5H); 3.57 and 3.59 (2s: 2H in total), 3.90 and 3.93 (2s: 3H in total); 5.25 (mt: 1H); 5.55 (mf: 1H); 7.22 (mt: 2H); from 7.25 to 7.45 (mt: 3H); 7.56 (mt: 1H); 7.94 (d, J = 9 Hz: 1H); 8.70 (d, J = 4.5 Hz: 1H); from 12.10 to 12.80 (mf spread: 1H). (3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenyl) prop-2-one) Methylpiperidine-3-carboxylate To a mixture of 0.95 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] Methyl 1- (prop-2-ynyl) piperidine-3-carboxylate in 9.5 cm3 of triethylamine, stirred at a temperature in the region of 20 ° C. under an inert atmosphere, 0.138 g of tetrakis triphenylphosphine palladium and 0.046 g of iodide are added. cuprous and 0.42 cc of 1-bromo-3,5-difluorobenzene. The mixture is heated at a temperature of 80 ° C for 3 hours. After cooling to about 20 ° C, the reaction mixture is taken up in 30 cm3 of ethyl acetate and 30 cm3 of water, stirred for 5 minutes. The organic phase is decanted while the aqueous layer is extracted with 2 times 30 cm3 of ethyl acetate. The organic extracts are combined, washed with 3 times 30 cm3 of water, dried over sodium sulphate, filtered and concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. The residue obtained is purified by chromatography under a nitrogen pressure of 50 kPa, on a column of silica gel (particle size 20-45 μ, diameter 2.3 cm, 40 g), eluting with pure ethyl acetate. first collect 2 fractions of 100 cm3, then fractions of 20 cm3 are carried out. Fractions 8 to 40 are combined and evaporated under the conditions of the above. 0.967 g of (3R, 4R) -4- {3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenyl) propane are obtained. Methyl 2-ynyl] piperidine-3-carboxylate, as an orange-colored meringue. x 120 22 257

Spectre infra-rouge (KBr) : 3424 ; 2948 ; 1734 ; 1618 ; 1586 ; 1432 ; 1242 ; 1122 ;1028 ; 990 ; 856 et 373 cm'1Infra-red spectrum (KBr): 3424; 2948; 1734; 1618; 1586; 1432; 1242; 1122; 1028; 990; 856 and 373 cm'1

Le (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-(prop-2-ynyl)pipéridine-3-carboxylate de méthyle peut être préparé comme décrit dansl’exemple 32.Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-carboxylate can be prepared as described in Example 32.

Exemple 51Example 51

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l- [3-(2,5-difIuorophényl)prop-2-ynyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,5-difluorophenyl) prop-2- acid ynyl] piperidine-3-carboxylic acid

Un mélange de 0,874 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,5-difluorophényl)prop-2-ynyl]pipéridine-3-carboxylate de méthyledans 8,8 cm3 de dioxanne additionnés de 1,37 cm3 de soude aqueuse 5N est agitépendant 17 heures à une température voisine de 60°C. Après refroidissement àenviron 20°C, le mélange réactionnel est évaporé sous pression réduite (5 kPa) à unetempérature voisine de 40°C. On obtient une huile que l’on purifie parchromatographie sous une pression de 50 kPa d’azote, sur une colonne de gel de silice(granulométrie 20-45μ ; diamètre 3 cm ; 25 g), en éluant par un mélange dedichlorométhane-méthanol (85/15 en volumes), en recueillant d’abord une fraction de100 cm3, puis des fractions de 50 cm3. Les fractions 3 et 4 sont réunies, concentréescomme ci-dessus. J Λ résidu d’évaporation est repris par du dichloroniéthane, filtré. Lefiltrat est concentré comme dans les conditions précédentes, puis le produit obtenu estrepris sous agitation par 40 cm3 d’un mélange de pentane-éther diisoprppylique(50/50 en volumes) pendant 16 heures à une température voisine de 20°C. Lescristaux obtenus sont essorés, lavés par 2 fois 10 cm3 du même mélange que ci-dessus, puis 3 fois 20 cm3 depentane. On obtient 0,392 g d’acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,5-difluorophényl)prop-2-ynyl]pipéridine-3-carboxylique, sous forme d’un solide jaune pâle fondant à 109°C,mélange de deux diastéréoisomères.A mixture of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,5-difluorophenyl), 0.874 g. ) Methyl prop-2-ynyl] piperidine-3-carboxylate in 8.8 cm3 of dioxane supplemented with 1.37 cm3 of 5N aqueous sodium hydroxide is stirred for 17 hours at a temperature in the region of 60 ° C. After cooling to about 20 ° C., the reaction mixture is evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. An oil is obtained which is purified by chromatography under a pressure of 50 kPa of nitrogen, on a column of silica gel (particle size 20-45 μ, diameter 3 cm, 25 g), eluting with a dichloromethane-methanol mixture ( 85/15 by volume), first collecting a fraction of 100 cm3, then fractions of 50 cm3. Fractions 3 and 4 are combined, concentrated as above. J Λ evaporation residue is taken up with dichloroethane, filtered. Lefiltrat is concentrated as in the previous conditions, then the product obtained is stirred under stirring with 40 cm3 of a mixture of pentane-diisoprypylic ether (50/50 by volume) for 16 hours at a temperature of 20 ° C. The crystals obtained are drained, washed with twice 10 cm 3 of the same mixture as above, then 3 times 20 cm 3 of depentane. 0.392 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,5- difluorophenyl) prop-2-ynyl] piperidine-3-carboxylic acid, in the form of a pale yellow solid melting at 109 ° C., a mixture of two diastereoisomers.

Spectre de R.M.N. (300 MHz, (CD3)2SO d6, δ en ppm). On observe un mélangede deux diastéréoisomères : de 1,40 à 2,00 (mts : 7H) ; de 2,30 à 3,00 (mt : 5H) ; 3,64 et 3,65 (2s : 2H en totalité) ;3,90 et 3,92 (2s : 3H en totalité) ; 5,26 (mf : 1H) ; 5,56 (mf : 1H) ; de 7,25 à 7,50 (mt : 258 120 2 2 5H) ; 7,56 (mt : 1H) ; 7,94 (d, J = 9 Hz : 1H) ; 8,71 (d, J = 4,5 Hz : 1H) ; de 12,40 à 12,70 (mf: 1H). (3R,4R)-4-[3-(R,S)-Hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,5-difluorophényl)prop-2-ynyl]pipéridine-3-carboxyIate de méthyle 5 Un mélange de 1,1 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-(prop-2-ynyl)pipéridine-3-carboxylate de méthyle, 11 cm3 de triéthylamine,0,16 cm3 de tétrakis triphénylphosphine palladium, 0,053 g d’iodure cuivreux et de0,47 cm3 de l-bromo-2,5-difluorobenzène est agité pendant 3 heures 15 minutes sousatmosphère "inerte à une température voisine de 80°C. Après refroidissement à environ 10 20°C, le mélange réactionnel est additionné de 30 cm3 d’acétate d’éthyle et 30 cm3 d’eau, sous agitation. La phase organique est séparée tandis que la phase aqueuse estextraite par 2 fois 30 cm3 d’acétate d’éthyle. Les extraits organiques sont réunis, lavéspar 3 fois 25 cm3 d’eau, séchés sur sulfate de sodium, concentrés sous pression réduite(5 kPa) à une température voisine de 40°C. On obtient un produit que l’on purifie par 15 chromatographie sous une pression de 50 kPa d’azote, sur une colonne de gel de silice(granulométrie 20-45μ ; diamètre 3,3 cm ; 50 g), en éluant par de l’acétate d’éthyle eten recueillant d’abord une fraction de 300 cm3, puis des fractions de 32 cm3. Lesfractions 7 à 22 sont réunies, puis concentrées dans les conditions de ci-dessus. Onobtient 0,91 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l- 20· [3-(2,5-difluorophényl)prop-2-ynyl]pipéridine-3-carboxylate de méthyle, sous formed’une meringue de couleur blanc cassé.Spectrum of R.M.N. (300 MHz, (CD3) 2SO d6, δ in ppm). A mixture of two diastereoisomers is observed: from 1.40 to 2.00 (mts: 7H); from 2.30 to 3.00 (mt: 5H); 3.64 and 3.65 (2s: 2H in total), 3.90 and 3.92 (2s: 3H in total); 5.26 (mf: 1H); 5.56 (mf: 1H); from 7.25 to 7.50 (mt: 258 120 2 2 5H); 7.56 (mt: 1H); 7.94 (d, J = 9 Hz: 1H); 8.71 (d, J = 4.5 Hz: 1H); from 12.40 to 12.70 (mf: 1H). (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -l- [3- (2,5-difluorophenyl) prop-2-ynyl ] Piperidine-3-carboxy methylate A mixture of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl], 1.1 g Methyl 1- (prop-2-ynyl) piperidine-3-carboxylate, triethylamine (11 cc), tetrakis triphenylphosphine palladium (0.16 cc), cuprous iodide (0.053 g), and bromo-2,5-bromo (0.47 cc). Difluorobenzene is stirred for 3 hours 15 minutes under-atmosphere "inert at a temperature of 80 ° C. After cooling to about 20 ° C, the reaction mixture is supplemented with 30 cm3 of ethyl acetate and 30 cm3 of water. The organic phase is separated while the aqueous phase is extracted with twice 30 cm 3 of ethyl acetate.The organic extracts are combined, washed with 3 times 25 cm 3 of water, dried over sodium sulfate, concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. a product which is purified by chromatography under a pressure of 50 kPa nitrogen, on a silica gel column (particle size 20-45μ; diameter 3.3 cm; 50 g), eluting with ethyl acetate and first collecting a fraction of 300 cm3, then fractions of 32 cm3. Fractions 7 to 22 are combined and then concentrated under the conditions of the above. 0.91 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,5 g) are obtained. Methyl-difluorophenyl) prop-2-ynyl] piperidine-3-carboxylate, as an off-white meringue.

Spectre infra rouge (CC14) : 3614 ; 2950 ; 1738 ; 1622 ; 1497 ; 1249 ; 1163 ; 1033 et873 cm'1Infra red spectrum (CCl4): 3614; 2950; 1738; 1622; 1497; 1249; 1163; 1033 and 873 cm -1

Le (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-(prop-2-ynyl) 25 pipéridine-3-carboxylate de méthyle a été préparé dans l’exemple 43.(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-carboxylate; methyl was prepared in Example 43.

Exemple 52Example 52

Acide (3R,4R)-l-[2-(cyclohexylthio)éthyl]-4-[3-hydroxy-3-(6-méthoxvquinolin-4- yl)propylJpipéridine-3-acétique, diastéréoisomère A et acide (3R,4R)-l-[2- (cyclohexylthio)éthyl]-4-[3-hydroxy-3-(6-méthoxyquinolin-4- 30 yl)propyl]pipéridine-3-acétique, diastéréoisomère B. 1 20 2 2 259 1,3 g d’acide (3R,4R)-l-[2-(cyclohexylthio)éthyl]-4-[3-(R,S)-hydroxy-3-(6-méthoxy-quinolin-4-yl)propyl3pipéridine-3-acétique est chromatographie sur une colonne de35 cm de long et 6 cm de diamètre, conditionnée avec 700 g de silice KROMASIL®(granulométrie 10μ). L’élution est effectuée à l’aide d’un mélange dedichlorométhane-acétonitrile-méthanol-triéthylamine (56/40/4/0,5 en volumes). Ledébit est de 70 cm’/mn. La détection est effectuée en ultra violet à 265 nm. Deuxinjections préparatives ont conduit à la séparation des 2 diastéréoisomères. Lesfractions correspondant au premier, le dastéréoisomère A, sont concentrées souspression réduite (5 kPa) à une température voisine de 40°C. Le résidu d’évaporationobtenu est séché à l’étuve, sous pression réduite (10 Pa) à une température voisine de20°C. On obtient 0,310 g d’acide (3R,4R)-l-[2-(cyclohexylthïo)éthyl]-4-(3-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-acétique, diastéréoisomère A, sousforme d’une meringue de couleur beige. (ctD20 = -43,6+/-1,0 dans le dichlorométhane à0,5 %). Les fractions correspondant au second, le diastéréoisomère B, sontconcentrées sous pression réduite (5 kPa) à une température voisine de 40°C. Lerésidu d’évaporation obtenu est séché à l’étuve, sous pression réduite (10 Pa) à unetempérature voisine de 20°C. On obtient 0,260 g d’acide (3R,4R)-l-[2-(cyclohexylthio)éthyl]-4-[3-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-acétique, diastéréoisomère B, sous forme d’une meringue de couleur beige. (aD20 =+55,4 +/-1,1 dans le dichlorométhane à 0,5%) diastéréoisomère A : Spectre de R.M.hJh (300 MHz, (CD3)2SO d6, δ en ppm) : de 1,10 λ 2,20 et de 2,30 à 2,80 (2 séries de mis : 29H en totalité) ; 3,93 (s : 3H) ; 5,28(dd large, J - 7,5 et 3 Hz : 1H) ; de 5,30 à 5,70 (mf étalé : 1H) ; de 7,35 à 7,45 (mt :2H) ; 7,56 (d, J = 4,5 Hz : 1H) ; 7,94 (d, J = 9,5 Hz : 1H) ; 8,72 (d, J = 4,5 Hz : 1H). diastéréoisomère B : Spectre de R.M.N.^H (300 MHz, (CD3)2SO d6, δ en ppm) : de 1,10 à 2,10 et de 2,30 à 2,80 (2 séries de mts : 29H en totalité) ; 3,92 (s : 3H) ; 5,27(dd large, J = 7,5 et 3 Hz : 1H) ; de 5,30 à 5,75 (mf étalé : 1H) ; de 7,35 à 7,45 (mt :2H) ; 7,54 (d, J = 4,5 Hz : 1H) ; 7,94 (d, J = 9,5 Hz : 1H) ; 8,71 (d, J = 4,5 Hz : 1H).(3R, 4R) -1- [2- (Cyclohexylthio) ethyl] -4- [3-hydroxy-3- (6-methoxvquinolin-4-yl) propyl] piperidine-3-acetic acid, diastereoisomer A and acid (3R, 4R) 1- [2- (cyclohexylthio) ethyl] -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetic acid, diastereoisomeric B 1 20 2 259 1, 3 g of (3R, 4R) -1- [2- (cyclohexylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxy-quinolin-4-yl) propyl] piperidine- 3-acetic acid is chromatographed on a column 35 cm long and 6 cm in diameter, conditioned with 700 g of silica KROMASIL® (particle size 10μ). The elution is carried out using a mixture of dichloromethane-acetonitrile-methanol-triethylamine (56/40/4 / 0.5 by volume). Ledebit is 70 cm / min. The detection is carried out in ultraviolet at 265 nm. Two preparatory injections led to the separation of the two diastereoisomers. The fractions corresponding to the first, the dasteroisomer A, are concentrated under reduced pressure (5 kPa) at a temperature of 40 ° C. The evaporation residue obtained is dried in an oven under reduced pressure (10 Pa) at a temperature in the region of 20 ° C. 0.310 g of (3R, 4R) -1- [2- (cyclohexylthio) ethyl] -4- (3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetic acid is obtained, diastereoisomer A, in the form of a beige meringue (ctD20 = -43.6 +/- 1.0 in 0.5% dichloromethane), the fractions corresponding to the second one, the diastereoisomer B, are concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. The evaporation residue obtained is dried in an oven under reduced pressure (10 Pa) at a temperature in the region of 20 ° C. 0.260 g of (3R, 4R) acid are obtained. 1- [2- (Cyclohexylthio) ethyl] -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetic acid, diastereoisomer B, as a beige meringue (aD20 = + 55.4 +/- 1.1 in 0.5% dichloromethane) diastereoisomer A: Spectrum of RMhJh (300 MHz, (CD3) 2SO d6, δ in ppm): 1.10 λ 2.20 and 2.30 to 2.80 (2 sets of mis: 29H in total), 3.93 (s: 3H), 5.28 (wide dd, J-7.5 and 3 Hz: 1H), 5.30 to 5.70 (mw spread: 1H), 7.35 to 7.45 (mt: 2H); 7.56 (d, J = 4.5 Hz: 1H); 7.94 (d, J = 9.5 Hz: 1H); 8.72 (d, J = 4.5 Hz: 1H). diastereoisomer B: 1 H NMR spectrum (300 MHz, (CD3) 2SO d6, δ in ppm): from 1.10 to 2.10 and from 2.30 to 2.80 (2 sets of mts: 29H in total) ; 3.92 (s: 3H); 5.27 (broad dd, J = 7.5 and 3 Hz: 1H); from 5.30 to 5.75 (mf spread: 1H); from 7.35 to 7.45 (mt: 2H); 7.54 (d, J = 4.5 Hz: 1H); 7.94 (d, J = 9.5 Hz: 1H); 8.71 (d, J = 4.5 Hz: 1H).

Acide (3R,4R)-l-[2-(cyclohexylthio)éthyl]-4-[3-(R,S)-hydroxy-3-(6- méthoxyquinolin-4-yl)propyl]pipéridine-3-acétique A une solution de 1,9 g de (3R,4R)-l-[2-(cyclohexylthio)éthyl]-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-acétate de méthyle dans 35 cm3 dedioxanne, on ajoute sous agitation à une température voisine de 20°C, 2,96 cm3 de 260 1 20 2 2 soude aqueuse 5N. La solution est chauffée pendant 16 heures à une températurevoisine de 60°C. Le mélange réactionnel est évaporé sous pression réduite (5 kPa) àune température voisine de 50°C, puis le résidu obtenu est repris par 50 cm3d’acétone, évaporé à nouveau comme ci-dessus. Après avoir repris le résidu obtenupar 50 cm3 d’éther diéthylique et concentré comme dans les conditions précédentes, lesolide jaune obtenu est additionné de 20 cm3 d’eau, acidifié par la quantité suffisanted’acide citrique pour obtenir un pH voisin de 4-5. Le mélange est extrait par 50 cm3de dichlorométhane. L’extrait organique est concentré sous pression réduite (5 kPa) àune température voisine de 50°C. Le résidu d’évaporation est repris par 2 fois100 cm3 d’un mélange de dichlorométhane-méthanol (90/10 en volumes), l’insolubleétant filtré après chaque reprise. Les filtrats réunis sont concentrés comme ci-dessus,puis le résidu obtenu est repris par 50 cm3 d’éther diéthylique, évaporé comme dansles conditions précédentes. Les cristaux obtenus sont repris dans 50 cm3 d’étherdiéthylique, filtrés, lavés par 2 fois 50 cm3 d’éther. Le produit est enfin séché souspression réduite, d’abord sous 5 kPa, puis à l’étuve sous 10 Pa, à une températurevoisine de 60°C. On obtient 1.9 g d’acide(3R,4R)-l-[2-(cyclohexylthio)éthyi]-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-acétique, sous formed’un solide de couleur jaune.(3R, 4R) -1- [2- (Cyclohexylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetic acid A a solution of (3R, 4R) -1- [2- (cyclohexylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl), 1.9 g. ] Piperidine-3-methyl acetate in 35 cm3 of dioxane, is added with stirring at a temperature of 20 ° C, 2.96 cm3 260 1 2 2 2 NaN aqueous soda. The solution is heated for 16 hours at a temperature of about 60 ° C. The reaction mixture is evaporated under reduced pressure (5 kPa) at a temperature in the region of 50 ° C., and the residue obtained is then taken up in 50 cm 3 of acetone, evaporated again as above. After taking up the residue obtained with 50 cm3 of diethyl ether and concentrated as in the preceding conditions, the yellow amide obtained is supplemented with 20 cm3 of water, acidified by the sufficient amount of citric acid to obtain a pH of about 4-5. The mixture is extracted with 50 cm3 of dichloromethane. The organic extract is concentrated under reduced pressure (5 kPa) at a temperature of 50 ° C. The evaporation residue is taken up in twice 100 cm3 of a mixture of dichloromethane-methanol (90/10 by volume), the insoluble being filtered after each recovery. The combined filtrates are concentrated as above, then the residue obtained is taken up in 50 cm3 of diethyl ether, evaporated as in the preceding conditions. The crystals obtained are taken up in 50 cm3 of diethyl ether, filtered and washed with twice 50 cm3 of ether. The product is finally dried under reduced pressure, firstly under 5 kPa, then in an oven under 10 Pa, at a temperature of 60 ° C. 1.9 g of (3R, 4R) -1- [2- (cyclohexylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] are obtained. piperidine-3-acetic acid, as a yellow solid.

Spectre de R.M.N. (300 MHz, (CD3)2SO d6, δ en ppm). On observe un mélangede deux diastéréoisomères : de 1,00 à 2,95 (mts : 29H) ; 3,92 (s : 3H) ; 5,27 (mt : 1H) ; 5,54 (mf : 1H) ; de 7,30 à 7,45 (mt : 2H) ; 7,55 (mt : 1H) ; 7,95 (d, J = 9,5 Hz : 1H) ; 8,72 (d, J = 4,5 Hz : 1H) ;de 10,80 à 11,90 (mf très étalé : 1H).Spectrum of R.M.N. (300 MHz, (CD3) 2SO d6, δ in ppm). A mixture of two diastereoisomers is observed: from 1.00 to 2.95 (mts: 29H); 3.92 (s: 3H); 5.27 (mt: 1H); 5.54 (mf: 1H); from 7.30 to 7.45 (mt: 2H); 7.55 (mt: 1H); 7.95 (d, J = 9.5 Hz: 1H); 8.72 (d, J = 4.5 Hz: 1H), from 10.80 to 11.90 (mf very spread: 1H).

Exemple 52AExample 52A

Dichlorhydrate du (3R,4R)-l-[2-(cyclohexyIthio)éthyl]-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-acétate de méthyle A une solution de 3,5 g de (3R,4R)-l-[2-(cyclohexylthio)éthyl]-4-[3-oxo-3-(6- méthoxyquinolin-4-yl)propyl]pipéridine-3-acétate de méthyle dans 50 cm3 de méthanol additionnés d’1 goutte de soude 5N, refroidie à une température voisine de» 15°C, on ajoute par petites fractions, en 1 heure environ, sous agitation et sousatmosphère inerte, 0,42 g de borohydrure de sodium. Le mélange est agité pendant2 heures à cette température, puis Refroidi aux environs de 10°C. On ajoute alorsgoutte à goutte 10 cm3 d’eau. Le mélange est concentré sous pression réduite (5 kPa) 120 2 2 261 à une température voisine de 45°C. Après addition de 100 cm3 d’eau au résidu obtenu,on extrait le mélange par 2 fois 100 cm3 d’acétate d’éthyle. Les extraits réunis sontséchés sur sulfate de sodium, filtrés, concentrés comme ci-dessus. On obtient unehuile que l’on purifie par chromatographie sous une pression de 50 kPa d’azote, surune colonne de gel de silice (granulométrie 20-45μ ; diamètre 3 cm ; hauteur 35 cm),en éluant par de l’acétate d’éthyle, et en recueillant des fractions de 30 cm3. Lesfractions 19 à 42 sont réunies, concentrées comme dans les conditions précédentes.On obtient 2,44 g d’un produit dont on fait le chlorhydrate de la façon suivante : Onsolubilise 0,5 g de produit dans 10 cm3 d’éther diéthylique, puis on verse la solutiondans 5 cm3 d’éther chlorhydrique IN. On ajoute 10 cm3 d’éther, puis on laisse agiterle mélange pendant 1 heure à une température voisine de 20°C. Le mélange est filtré,le gâteau lavé par 2 fois 10 cm3 d’éther diéthylique, séché sous pression réduite(5 kPa) à une température voisine de 20°C, puis à l’étuve sous pression réduite(10 Pa) à une température voisine de 60°C. On obtient 0,46 g de dichlorhydrate du(3R,4K)-l-[2-(cycIohexylthio)éthyl]-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-acétate de méthyle, sous forme d’un solide de couleur rose pâle,fondant à 80°C en se ramollissant.(3R, 4R) -1- [2- (Cyclohexylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate dihydrochloride To a solution of 3.5 g of (3R, 4R) -1- [2- (cyclohexylthio) ethyl] -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine 3-methyl acetate in 50 cm3 of methanol added with 1 drop of 5N sodium hydroxide, cooled to a temperature in the region of -15 ° C., 0.42 is added in small portions over approximately 1 hour, with stirring and inert atmosphere. g sodium borohydride. The mixture is stirred for 2 hours at this temperature and then cooled to about 10 ° C. 10 cm3 of water are then added drop by drop. The mixture is concentrated under reduced pressure (5 kPa) at a temperature in the region of 45 ° C. After addition of 100 cm3 of water to the residue obtained, the mixture is extracted with twice 100 cm3 of ethyl acetate. The combined extracts are dried over sodium sulphate, filtered and concentrated as above. An oil is obtained which is purified by chromatography under a pressure of 50 kPa of nitrogen, on a column of silica gel (granulometry 20-45μ, diameter 3 cm, height 35 cm), eluting with sodium acetate. ethyl, and collecting fractions of 30 cm3. Fractions 19 to 42 are combined, concentrated as in the preceding conditions. 2.44 g of a product of which the hydrochloride is obtained are obtained in the following manner: 0.5 g of product is dissolved in 10 cm of diethyl ether, and then the solution is poured into 5 cm3 of 1N hydrochloric ether. 10 cm3 of ether are added, and then the mixture is stirred for 1 hour at a temperature in the region of 20 ° C. The mixture is filtered, the cake washed with twice 10 cm3 of diethyl ether, dried under reduced pressure (5 kPa) at a temperature in the region of 20 ° C. and then in an oven under reduced pressure (10 Pa) at a temperature of close to 60 ° C. 0.46 g of (3R, 4K) -1- [2- (cyclohexylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl)) dihydrochloride is obtained propyl] piperidine-3-methyl acetate, in the form of a pale pink solid, melting at 80 ° C while softening.

Spectre de R.M.N. (400 MHz, (CD3)2SO d6 à une température de 383K, δ enppm). On observe un mélange de deux diastéréoisomères : de 1,20 à 2,05 et de 2,30 à 2,65 (mis : 20H en totalité) ; 2.82 (mt : III) ; de 2,85 à 3,50(rnf étalé : 411) ; 2,96 (mt : 2H) ; 3,19 (mt : 2H) ; 3,02 et 3,63 (2s : 3H en totalité) ;4,00 (s : 3H) ; 5,37 (mt : Pi) ; de 7,50 à 7,65 (mt : 211.) ; 7,73 (mf : 1 H) ; 8,15 (dlarge, J = 9 Hz : 1H) ; 8,83 (d, J - 4,5 Hz : 1H). (3R,4R)-l-(2-(Cyclohexylthio)éthylJ-4-[3-oxo-3-(6-méthoxyquinoIin-4-yî)propyl]pipéridine-3-acétate de méthyle A une solution de 3,9 g de (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-acétate de méthyle dans 50 cm3 d’acétonitrile, on ajoute sous agitation àune température voisine de 20°C, et sous atmosphère inerte, 2,06 g de 2-chloroéthylcyclohexyl sulfure, 50 cm3 d’acétonitrile, puis 1,78 g d’iodure depotassium et 7,25 g de carbonate de potassium. Le mélange est chauffé pendant18 heures à une température voisine de 80°C. Après refroidissement à environ 20°C,le mélange est additionné de 100 cm3 d’eau et 100 cm3 d’acétate d’éthyle. La phaseorganique est décantée tandis que la phase aqueuse est extraite par 200 cm3 d’acétate 120 2 2 262 d’éthyle. Les extraits organiques sont réunis, séchés sur sulfate de sodium, filtrés,concentrés sous pression réduite (5 kPa) à une température voisine de 45°C. Onobtient une huile que l’on purifie par chromatographie sous une pression de 50 kPad’azote, sur une colonne de gel de silice (granulométrie 20-45μ ; diamètre 3,5 cm ;hauteur 46 cm) en éluant par un mélange de dichlorométhane-méthanol (95/5 envolumes) et en recueillant des fractions de 50 cm3. Les fractions 18 à 37 sont réunies,concentrées comme ci-dessus. On obtient un produit que l’on purifie une seconde foispar chromatographie sous une pression de 50 kPa d’azote, sur une colonne de gel desilice (granulométrie 20-45μ ; diamètre 4 cm ; hauteur 40 cm) en éluant par unmélange d’acétate d’èthyle-cyclohexane (7/3 en volumes) et en recueillant desfractions de 100 cm3. Les fractions 24 à 54 sont réunies puis concentrées dans lesmêmes conditions que précédemment. On obtient 3,7 g de (3R,4R)-l-[2-(cyclohexylthio)éthyl]-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-acétate de méthyle, sous forme d’une huile de couleur brune.Spectrum of R.M.N. (400 MHz, (CD3) 2SO d6 at a temperature of 383K, δ enppm). There is a mixture of two diastereoisomers: 1.20 to 2.05 and 2.30 to 2.65 (set: 20H in total); 2.82 (mt: III); from 2.85 to 3.50 (spread rnf: 411); 2.96 (mt: 2H); 3.19 (mt: 2H); 3.02 and 3.63 (2s: 3H in total), 4.00 (s: 3H); 5.37 (mt: Pi); from 7.50 to 7.65 (mt: 211.); 7.73 (mf: 1H); 8.15 (broad, J = 9 Hz: 1H); 8.83 (d, J - 4.5 Hz: 1H). (3R, 4R) -1- (2- (Cyclohexylthio) ethyl] -4- [3-oxo-3- (6-methoxyquinyl-4-yl) propyl] piperidine-3-methyl acetate to a solution of 3.9 of methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate in 50 cm3 of acetonitrile is added with stirring to a temperature of 20 ° C., and under an inert atmosphere, 2.06 g of 2-chloroethylcyclohexyl sulphide, 50 cm3 of acetonitrile, then 1.78 g of potassium iodide and 7.25 g of potassium carbonate, the mixture is heated for 18 hours. at a temperature in the region of 80 ° C. After cooling to approximately 20 ° C., the mixture is treated with 100 cm 3 of water and 100 cm 3 of ethyl acetate, the organic phase is decanted while the aqueous phase is extracted with 200 ml of water. The ethyl extracts are combined, dried over sodium sulphate, filtered and concentrated under reduced pressure (5 kPa) at a temperature in the region of 45 ° C. An oil is obtained. that is purified by chromatography under a pressure of 50 kPad'azote, on a column of silica gel (particle size 20-45μ; diameter 3.5 cm, height 46 cm) eluting with a mixture of dichloromethane-methanol (95/5 volumes) and collecting 50 cm3 fractions. Fractions 18 to 37 are combined, concentrated as above. A product is obtained which is purified a second time by chromatography under a pressure of 50 kPa of nitrogen, on a desilice gel column (particle size 20-45μ, diameter 4 cm, height 40 cm), eluting with an acetate mixture. of ethyl-cyclohexane (7/3 by volume) and collecting fractions of 100 cm3. Fractions 24 to 54 are combined and then concentrated under the same conditions as above. 3.7 g of (3R, 4R) -1- [2- (cyclohexylthio) ethyl] -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate are obtained. methyl, in the form of a brown oil.

Spectre infra rouge (CH2C12) : 2933 ; 2855 ; 1732 ; 1693 ; 1620 ; 105 ; 1244 ; 1029 et853 cm'1Infra red spectrum (CH2Cl2): 2933; 2855; 1732; 1693; 1620; 105; 1244; 1029 and 853 cm -1

Le (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-acétate deméthyle a été obtenu dans l’exemple 48.(3R, 4R) -4- [3-Oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-methyl acetate was obtained in Example 48.

Exemple 53Example 53

Acide (3R,4R)-4-[3-hydroxy-3-(6-méthoxyquinolin-4-yI)propyl]-l-[3-(thién-2-yl)prop-2-ynyI)pipéridine-3-acétique, diastéréoisomère A et acide (3R,4R)-4-[3-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thién-2-yl)prop-2- ynyl]pipéridine-3-acétique, diastéréoisomère B. 1,2 g d’acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyI]-l -[3-(thién-2-yl)prop-2-ynyl]pipéridine-3-acétique est chromatographié sur une colonne de35 cm de long et 6 cm de diamètre, conditionnée avec 700 g de silice KROMASIL®(granulométrie 10μ). L’élution est effectuée à l’aide d’un mélange dedichlorométhane-acétonitrile-méthanol-triéthylamine (70/15/15/0,05 en volumes). Ledébit est de 90 cm3/mn. La détection est effectuée en ultra violet à 265 nm. Deuxinjections préparatives ont conduit à la séparation des 2 diastéréo^somères. Lesfractions correspondant au premier, le diastéréoisomère A, sont concentrées souspression réduite (5 kPa) à une température voisine de 40°C. La masse cristallineobtenue est séchée à l’étuve sous pression réduite (10 Pa) à une température voisine 120 2 2 263 de 20°C. On obtient 0,408 g d’acide (3R,4R)-4-[3-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(thién-2-yl)prop-2-ynyl]pipéridine-3-acétique, diastéréoisomère A,sous forme d’un solide de couleur jaune. (aD20 = -62,9+/-1,3 dans le méthanol à0,5 %). Les fractions correspondant au second, . le diastéréoisomère B, sont 5 concentrées sous pression réduite (5 kPa) à une température voisine de 40°C. Lamasse cristalline obtenue est séchée à l’étuve sous pression réduite (10 Pa) à unetempérature voisine de 20°C. On obtient 0376 g d’acide (3R,4R)-4-[3-hydroxy-3-(6-méthoxyquinolin-4-yl)propylj-l-[3-(thién-2-yl)prop-2-ynyl]pipéridine-3-acétique,diastéréoisomère B, sous forme d’un solide de couleur jaune. (aD20 = +46,9 +/-1,1 10 dans le méthanol à 0,5%) diastéréoisomère A : Spectre de R.M.N.^H (300 MHz, (CD3)2SO d6 avec ajout dequelques gouttes de CD3COOD d4, δ en ppm) : de 1,20 à 2,00 et de 2,05 à 2,50 (2séries de mts : 12H en totalité) ; de 2,60 à 2,85 (mt : 2H) ; 3,55 (AB limite, J - 17Hz : 2H) ; 3,90 (s : 3H) ; 5,27 (dd, J = 8 et 3 Hz : 1H) ; 7,04 (mt : 1H) ; 7,26 (d large, 15 J= 4Hz: 1H) ; de 7,30 à 7,45 (mt : 2H) ; 7,52 (d, J = 5,5 Hz : 1H) ; 7,56 (d, J = 4,5Hz : 1H) ; 7,93 (d, J = 10 Hz : 1H) ; 8,70 (d, J = 4,5 Hz : 1H). diastéréoisomère B : Spectre de R.M.NJH (300 MHz, (CD3)2SO d6 avec ajout dequelques gouttes de CD3COOD d4, δ en ppm) : de 1,20 à 1,90 et de 2,00 à 2,45 (2séries de mts : 12H en totalité) ; de 2,60 à 2,85 (mt : 2H) ; 3,50 (AB, J — 17 Hz : 2H) ; 20 3,91 (s : 3H) ; 5,27 (dd, J - 8 et 3,5 Hz : 1H) ; 7,05 (dd, J - 5,5 et 4 Hz : 1H) ; 7,26 (d large, J - 4 Hz : 1H) ; de 7,35 à 7,45 (mî : 2H) ; de 7,50 à 7,60 (mt : 2H) ; 7,95 (d, J- 10 Hz : JH) ; 8,71 (d, J = 4,5 Hz : 1H).(3R, 4R) -4- [3-Hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ylyl) piperidine-3- acid acetic acid, diastereoisomer A and (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl) ] piperidine-3-acetic acid, diastereoisomer B. 1.2 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] - 1 - [3- (thien-2-yl) prop-2-ynyl] piperidine-3-acetic acid is chromatographed on a column 35 cm long and 6 cm in diameter, conditioned with 700 g of silica KROMASIL® (particle size 10 μ) . The elution is carried out using a mixture of dichloromethane-acetonitrile-methanol-triethylamine (70/15/15 / 0.05 by volume). Ledebit is 90 cm3 / min. The detection is carried out in ultraviolet at 265 nm. Two preparatory injections led to the separation of the two diastereomers. Fractions corresponding to the first, diastereoisomer A, are concentrated under reduced pressure (5 kPa) at a temperature of 40 ° C. The crystalline mass obtained is dried in an oven under reduced pressure (10 Pa) at a temperature in the region of 20.degree. 0.408 g of (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-) acid is obtained. ynyl] piperidine-3-acetic acid, diastereoisomer A, as a yellow solid. (aD20 = -62.9 +/- 1.3 in 0.5% methanol). Fractions corresponding to the second,. the diastereoisomer B, are concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. Crystalline lime obtained is dried in an oven under reduced pressure (10 Pa) at a temperature of 20 ° C. 0376 g of (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl) acid are obtained. ] piperidine-3-acetic acid, diastereoisomer B, as a yellow solid. (aD20 = +46.9 +/- 1.1 in 0.5% methanol) diastereoisomer A: 1 H NMR spectrum (300 MHz, (CD3) 2SO d6 with addition of some drops of CD3COOD d4, δ in ppm): from 1.20 to 2.00 and from 2.05 to 2.50 (2 sets of mts: 12H in total); from 2.60 to 2.85 (mt: 2H); 3.55 (AB limit, J - 17Hz: 2H); 3.90 (s: 3H); 5.27 (dd, J = 8 and 3 Hz: 1H); 7.04 (mt: 1H); 7.26 (broad d, J = 4Hz: 1H); from 7.30 to 7.45 (mt: 2H); 7.52 (d, J = 5.5 Hz: 1H); 7.56 (d, J = 4.5Hz: 1H); 7.93 (d, J = 10 Hz: 1H); 8.70 (d, J = 4.5 Hz: 1H). diastereoisomer B: 1 H NMR spectrum (300 MHz, (CD3) 2SO d6 with some drops of CD3COOD d4, δ in ppm): 1.20 to 1.90 and 2.00 to 2.45 (2 series of mts : 12H in total); from 2.60 to 2.85 (mt: 2H); 3.50 (AB, J - 17 Hz: 2H); 3.91 (s: 3H); 5.27 (dd, J - 8 and 3.5 Hz: 1H); 7.05 (dd, J - 5.5 and 4 Hz: 1H); 7.26 (broad d, J - 4 Hz: 1H); 7.35 to 7.45 (m: 2H); from 7.50 to 7.60 (mt: 2H); 7.95 (d, J-10 Hz: JH); 8.71 (d, J = 4.5 Hz: 1H).

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyI]-l-[3-(thién-2-yI)prop-2-ynyl]pipéridine-3~acétique 25 Une solution de 3 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thién-2-yl)prop-2-ynyî]pipéridine-3-acétate de méthyle dans 50 cm3 dedioxanne, additionnée de 5 cm3 de soude aqueuse 5N, est chauffée pendant 17 heuresà une température voisine de 60°C, sous agitation et sous atmosphère inerte. Aprèsrefroidissement à environ 20°C, le mélange est concentré sous pression réduite 30 (5 kPa) à une température voisine de 40°C, puis le résidu est repris par 100 cm3 de dichlorométhane et 5 cm3 d’eau. Le mélange est acidifié par la quantité suffisanted’acide citrique pour obtenir un pH voisin de 4-5, puis séché sur sulfate demagnésium, filtre, concentré comme ci-dessus. L’eau résiduelle est entraînée par 120 2 2 264 azéotropie dans le chloroforme. Après concentration comme précédemment, le résiduobtenu est purifié par chromatographie à pression atmosphérique sur une colonne degel de silice (granulométrie 20-45μ ; diamètre 3,5 cm ; volume de silice 200 cm3), enéluant par un mélange de chloroforme-méthanol-ammoniaque à 28% (12/3/0,5 envolumes) et en recueillant des fractions d’environ 60 cm3. Les fractions contenant leproduit attendu sont réunies, puis concentrées sous pression réduite (5 kPa) à unetempérature voisine de 40°C. Le résidu obtenu est repris par 40 cm3 d’étherdiéthylique, essoré, lavé par 2 fois 5 cm3 d’éther, séché sous pression réduite (5 kPa) àune température voisine de 20°C, puis à l’étuve sous pression réduite (10 Pa) à unetempérature voisine de 40°C. On obtient 1,9 g d’acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thién-2-yl)prop-2-ynyl]pipéridine-3-acétique,sous forme d’un solide blanc.(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2- acid) 3 g (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3-yl] piperidine-acetic acid Methyl 3- (thien-2-yl) prop-2-ynyl] piperidine-3-acetate in 50 cm3 of dioxane, added with 5 cm3 of 5N aqueous sodium hydroxide, is heated for 17 hours at a temperature in the region of 60.degree. agitation and under an inert atmosphere. After cooling to about 20 ° C, the mixture is concentrated under reduced pressure (5 kPa) at a temperature of 40 ° C, and the residue is taken up in 100 cm3 of dichloromethane and 5 cm3 of water. The mixture is acidified by the sufficient amount of citric acid to obtain a pH of about 4-5, and then dried over magnesium sulfate, filter, concentrated as above. The residual water is entrained by azeotropy in chloroform. After concentration as above, the residue obtained is purified by chromatography at atmospheric pressure on a silica-thaw column (particle size 20-45μ, diameter 3.5 cm, volume of silica 200 cm 3), eluting with a mixture of chloroform-methanol-aqueous ammonia. 28% (12/3 / 0.5 volume) and collecting fractions of about 60 cm3. The fractions containing the expected product are combined and then concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. The residue obtained is taken up in 40 cm3 of diethyl ether, drained, washed with twice 5 cm3 of ether, dried under reduced pressure (5 kPa) at a temperature in the region of 20 ° C. and then in an oven under reduced pressure (10 ° C.). Pa) at a temperature of about 40 ° C. 1.9 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien) 2-yl) prop-2-ynyl] piperidine-3-acetic acid as a white solid.

Spectre de R.M.N. (300 MHz, (CD3)2SO d6, δ en ppm). On observe un mélangede deux diastéréoisomères : de 1,20 à 2,45 (mts : 12H) ; de 2,60 à 2,85 (mt : 2H) ; 3,48 (mt : 2H) ; 3,92 (s : 3H) ; 5,28 (mt : 1H) ; 7,06 (dd, J = 5,5 et 3,5 Hz : 1H) ; 7,27 (dd, J = 3,5 et 1 Hz : 1H) ; de7,30 à 7,45 (mt : 2H) ; de 7,50 à 7,60 (mt : 2H) ; 7,94 (d, J = 9 Hz : 1H) ; 8,70 (d, J = 4,5 Hz : 1H).Spectrum of R.M.N. (300 MHz, (CD3) 2SO d6, δ in ppm). There is a mixture of two diastereoisomers: from 1.20 to 2.45 (mts: 12H); from 2.60 to 2.85 (mt: 2H); 3.48 (mt: 2H); 3.92 (s: 3H); 5.28 (mt: 1H); 7.06 (dd, J = 5.5 and 3.5 Hz: 1H); 7.27 (dd, J = 3.5 and 1 Hz: 1H); from 7.30 to 7.45 (mt: 2H); from 7.50 to 7.60 (mt: 2H); 7.94 (d, J = 9 Hz: 1H); 8.70 (d, J = 4.5 Hz: 1H).

Exemple 53A (3R,4R)-4-[3-(R5S)-Hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thién-2-yl)prop-2-ynyl]pipéridine-3-acétate de méthyle A une solution de 4,0 g de (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thién-2-yl)prop-2-ynyl]pipéridine-3-acétate de méthyle dans 65 cm3 de méthanol,additionnée d’une goutte de soude aqueuse 5N, on ajoute en 40 minutes environ, àune température inférieure à 30°C, sous agitation et sous atmosphère inerte, 0,317 gde borohydrure de sodium. Après 3 heures d’agitation à une température voisine de20°C, le mélange est additionné de 100 cm3 d’eau, puis extrait par 4 fois 50 cm3 dedichlorométhane. Les extraits sont lavés par 3 fois 50 cm3 d’eau, séchés sur sulfate demagnésium, filtrés, concentrés sous pression réduite (5 kPa) à une température voisine de 40°C. On obtient une huile que l’on purifie par chromatographie à pression « atmosphérique, sur une colonne de gel de silice (granulométrie 20-45μ ; diamètre3,2xcm ; volume de silice 300 cm3), en éluant par l’acétate d’éthyle et en recueillantdes fractions d’environ 100 cm3. On réunit les fractions correspondant au produit 120 2 2 265 attendu. Celles-ci sont concentrées comme ci-dessus. On obtient 3,5 g de (3R,4R)-4-[3-(R,S)-hydroxy-3 -(6-méthoxyquinolin-4-yl)propyl]-1 -[3 -(thién-2-y!)prop-2-ynyl]pipéridine-3-acétate de méthyle, sous forme d’une huile de couleur jaune.Example 53A (3R, 4R) -4- [3- (R5S) -Hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl) ] Piperidine-3-methyl acetate To a solution of (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (3- thien-2-yl) prop-2-ynyl] piperidine-3-methyl acetate in 65 cm3 of methanol, added with a drop of 5N aqueous sodium hydroxide, is added in about 40 minutes to a temperature below 30 ° C, under stirring and under an inert atmosphere, 0.317 g of sodium borohydride. After stirring for 3 hours at a temperature in the region of 20 ° C., 100 cm3 of water are added to the mixture and then extracted with 4 times 50 cm3 of dichloromethane. The extracts are washed with water (3 × 50 cc), dried over magnesium sulphate, filtered and concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. An oil is obtained which is purified by atmospheric pressure chromatography, on a column of silica gel (particle size 20-45μ, diameter 3.2xcm, volume of silica 300 cm 3), eluting with ethyl acetate and collecting fractions of about 100 cm3. The fractions corresponding to the expected product 120 2 2 265 are pooled. These are concentrated as above. 3.5 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3 - (6-methoxyquinolin-4-yl) propyl] -1 - [3 - (thien-2-one) are obtained. y!) prop-2-ynyl] piperidine-3-methyl acetate as a yellow oil.

Spectre infrarouge (CCIJ : 2939; 1739;1622;1509;1434; 1241 ;850 et 696 cm'1Infrared spectrum (CCIJ: 2939; 1739; 1622; 1509; 1434; 1241; 850 and 696 cm -1)

On a préparé le chlorhydrate de la façon suivante : Une solution de 0,5 g de (3R,4R)- 4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thién-2-yI)prop-2-ynyl]pipéridine-3-acétate de méthyle dans 20 cm3 de dichlorométhane est ajoutée sousagitation à 30 cm3 d’éther diéthylique additionnés de 4 cm3 d’éther chlorhydrique IN.Au bout de 2 heures, le solide blanc formé est filtré, lavé par 2 fois 5 cm3d’étherdiéthylique, séché sous pression partielle (5 kPa), puis à poids constant, à l’étuve,sous pression réduite (10 Pa) à une température voisine de 40°C. On obtient 0,35 g dedichlorhydrate de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[3-(thién-2-yl)prop-2-ynyl]pipéridine-3-acétate de méthyle, sous forme d’un solideblanc.The hydrochloride was prepared as follows: A solution of 0.5 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] Methyl 1- [3- (thien-2-yl) prop-2-ynyl] piperidine-3-acetate in 20 cm3 of dichloromethane is added under stirring to 30 cm3 of diethyl ether supplemented with 4 cm3 of 1N hydrochloric ether. After 2 hours, the white solid formed is filtered, washed with 2 times 5 cm3 of diethyl ether, dried under partial pressure (5 kPa), then at constant weight, in an oven, under reduced pressure (10 Pa) at room temperature. a temperature close to 40 ° C. 0.35 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2) dihydrochloride are obtained. Methyl-propyl-2-ynyl] piperidine-3-acetate in the form of a solid white.

Spectre infra rouge (KBr) : 3278 ; 2932 ; 2524 ; 1730 ; 1619 ; 1601 ; 1427 ; 1248 ;1021 ; 849 et 714 cm'1 (3R,4R)-4-[3-Oxo-3-(6-méthoxyquinoIin-4-yl)propyl]-l-l3-(thién-2-yl)prop-2-ynyI]pipéridine-3-acétate de méthyle A une solution de 4,3 g de (3R,4R)-4-[3-oxo-3-(6-métlioxyquinoliri-4-yl)propyl]-l-(prop-2-ynyl]pipéridine-3-aeétate de méthyle dans 100 cm3 d’acétonitrile , on ajoutesous agitation à une température voisine de 20°C et sous atmosphère inerte, 0,263 gde triphénylphosphine, puis 0,85 g de tétrakis triphénylphosphine palladium, 0,4 gd’iodure cuivreux, 1,75 cm3 de 2-iodothiophène. On agite pendant 10 minutes lemélange, puis on ajoute 2,95 cm3 de triéthylamine. Après 48 heures d’agitation à unetempérature voisine de 20°C, le mélange est filtré sur célite, l’insoluble lavé par 2 fois50 cm3 d’acétonitrile. Le filtrat est concentré sous pression réduite (5 kPa) à unetempérature voisine de 40°C. Le résidu d’évaporation est purifié par chromatographieà pression atmosphérique sur une colonne de gel de silice (granulométrie 20-45μ ;diamètre 4,5 cm ; volume de silice 500 cm3), en éluant par de l’acétate d’éthyle pur eten recueillant des fractions d’environ 60 cm3. On réunit les fractions correspondant auproduit attendu. Celles-ci sont concentrées dans les conditions de ci-dessus. Onobtient 4 g de (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(thién-2- 266 120 2 2 yl)prop-2-ynyl]pipéridine-3-acétate de méthyle, sous forme d’une huile de couleurjaune.Infra red spectrum (KBr): 3278; 2932; 2524; 1730; 1619; 1601; 1427; 1248; 1021; 849 and 714 cm -1 (3R, 4R) -4- [3-Oxo-3- (6-methoxyquinin-4-yl) propyl] -1-1,3- (thien-2-yl) prop-2-yn]] piperidine-3-methyl acetate to a solution of (3R, 4R) -4- [3-oxo-3- (6-methylquinoquinol-4-yl) propyl] -1- (prop-2-), 4.3 g Methyl piperidine-3-acetate in 100 cm3 of acetonitrile, stirring at a temperature in the region of 20 ° C. under an inert atmosphere, 0.263 g of triphenylphosphine and 0.85 g of tetrakis triphenylphosphine palladium, 0.4 g. Cuprous iodide, 1.75 cm3 of 2-iodothiophene The mixture is stirred for 10 minutes, then 2.95 cm3 of triethylamine are added and the mixture is filtered on celite after stirring for 48 hours at a temperature in the region of 20 ° C. the insoluble material is washed with twice 50 cm3 of acetonitrile and the filtrate is concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. The evaporation residue is purified by chromatography at atmospheric pressure on a column of silica gel (granulométr ie 20-45μ, diameter 4.5 cm, volume of silica 500 cm3), eluting with pure ethyl acetate and collecting fractions of about 60 cm3. The fractions corresponding to the expected product are combined. These are concentrated under the conditions of above. 4 g of (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) 2-yl) prop-2 are obtained. -ynyl] piperidine-3-methyl acetate, in the form of a yellow-colored oil.

Spectre infra rouge (CCI,) : 2935 ; 1740 ; 1692 ; 1620 ; 1431 ; 1242 ; 1032 ; 849 et698 cm-' (3R,4R)-4-[3-Oxo-3-(6-méthoxyquinolin-4-yI)propyI]-l-(prop-2-ynyI]pipéridine- 3-acétate de méthyle A une solution de 5 g de (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-acétate de méthyle dans 60 cm3 de diméthylformamide, on ajoute sousagitation à une température voisine de 20°C et sous atmosphère inerte, 4,8 cm3 detriéthylamine. Après 15 minutes d’agitation à cette température, on ajoute en15 minutes environ 1,5 cm3 de bromure de propargyle, puis au bout de 15 minutes lemélange est chauffé à une température voisine de 45 °C pendant 4 heures. Aprèsrefroidissement à environ 20°C, le mélange réactionnel est versé sur environ 700 cm3d’eau, puis le mélange est extrait par 4 fois 80 cm3d’éther diéthylique. Les extraitsréunis sont lavés par 3 fois 80 cm3 d’eau, séchés, filtrés, concentrés sous pressionréduite (5 kPa) à une température voisine de 40°C. Le résidu d’évaporation est purifiépar chromatographie à pression atmosphérique sur une colonne de gel de silice(granulométrie 20-45μ ; diamètre 4 cm ; volume de silice 500 cm3), en éluant par del’acétate d’éthyle pur et en recueillant des fractions de 60 cm3. Les fractions 9 à20 sont réunies puis concentrées comme dans les conditions précédentes. On obtient 4,3 g de (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]-l-(prop-2-ynyl]pipéridine-3-acétate de méthyle, sous forme d’une huile de couleur jaune.Infrared spectrum (ITC): 2935; 1740; 1692; 1620; 1431; 1242; 1032; 849 and 698 cm -1- (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-methyl acetate. solution of 5 g of methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate in 60 cm 3 of dimethylformamide, sub-stirring at a temperature of At about 20 ° C and under an inert atmosphere, 4.8 cm 3 of triethylamine After stirring for 15 minutes at this temperature, 1.5 cm 3 of propargyl bromide are added over 15 minutes, and then after 15 minutes the mixture is heated to room temperature. a temperature of about 45 ° C. for 4 hours After cooling to about 20 ° C., the reaction mixture is poured onto about 700 cm 3 of water, and then the mixture is extracted with 4 times 80 cm 3 of diethyl ether. 80 cm3 of water are added, dried, filtered and concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. The evaporation residue is purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45μ; diameter 4 cm; silica volume 500 cm 3), eluting with pure ethyl acetate and collecting 60 cm 3 fractions. Fractions 9 to 20 are combined and then concentrated as in the previous conditions. 4.3 g of methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-acetate are obtained in the form of a yellow oil.

Spectre infra rouge (CC14) : 3311 ; 2936 ; 1739 ; 1692 ; 1620 ; 1431 ; 1242 ; 1032 ;849 ; 654 et 627 cm'1Infrared spectrum (CCl4): 3311; 2936; 1739; 1692; 1620; 1431; 1242; 1032; 849; 654 and 627 cm-1

Le (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-acétate deméthyle a été préparé dans l’exemple 48.(3R, 4R) -4- [3-Oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-methyl acetate was prepared in Example 48.

Exemple 54Example 54

Acide (3R,4R)-4-[3-hydroxy-3-(6-méthoxyquinolin-4-yl)propyIJ-l-(2- (cycIopentylthio)éthyl]pipéridine-3-acétique, diastéréoisomère A etdichlorhydrate de l’acide (3R,4R)-4-[3-hydroxy-3-(6-méthoxyquinolin-4-yI)propyi]-l-[2-(cycîopentylthio)éthyl]pipéridine-3-acétique, diastéréoisomère B. 267 120 2 2(3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (2- (cyclopentylthio) ethyl] piperidine-3-acetic acid, diastereoisomer A and acid dihydrochloride (3R, 4R) -4- [3-Hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-3-acetic acid, diastereoisomer B. 267 120 2 2

En opérant comme décrit dans l’exemple 52, les deux diastéréoisomères de l’acide(3 R,4R)-4- [3-(R,S)-hydroxy-3 -(6-méthoxyquinolin-4-yl)propy 1] -1 -[2 -cyclopentylthio) éthyl]pipéridine-3-acétique ont été séparés. On isole ainsi l’acide(3R,4R)-4-[3-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(cyclopentylthio)éthyl]pipéridine-3-acétique, diastéréoisomère B, sous forme d’unsolide de couleur blanche dont on fait le dichlorhydrate. (aD20 = -89,6 +/-1,6 dans leméthanol à 0,5 %), et l’acide (3R,4R)-4-[3-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(cyclopentylthio)éthyl]pipéridine-3-acétique, diastéréoisomère A, sousforme d’une huile épaisse de couleur jaune. (aD20 = +57,4 +/-0,9 dans le méthanol à0,5%). diastéréoisomère A : Spectre de R.M.N.^H (300 MHz, (CD3)2SO d6, δ en ppm) : de 1,15 à 2,10 et de 2,25 à 2,60 (mis : 24H en totalité) ; 2,70 (mt : 2H) ; 3,11 (mt : 1H) ; 3,92 (s : 3H) ; 5,26 (dd, J = 8 et 4 Hz : 1H) ; de 7,35 à 7,45 (mt : 2H) ; 7,54 (d, J = 4,5Hz : 1H) ; 7,94 (d, J = 10 Hz : 1H) ; 8,71 (d, J = 4,5 Hz : 1H). diastéréoisomère B : Spectre de R.M.N.^H (300 MHz, (CD3)2SO d6, δ en ppm).de1,30 à 2,10 - de 2,15 à 2,40 et de 2,65 à 3,50 (mts : 27H en totalité) ; 4,00 et 4,01 (2s :3H en totalité) ; 5,50 (mt : 1H) ; 7,54 et 7,58 (2d, J = 2,5 Hz : 1H en totalité) ; 7,71 (dtrès large, J = 9 Hz : 1H) ; 7,96 (mt : 1H) ; 8,23 (d très large, J = 9 Hz : 1H) ; 9,00 (dtrès large, J - 4,5 Hz : 1H) ; de 9,70 à 9,85 et de 10,15 à 10,35 (2mfs : 1H en totalité).Working as described in Example 52, the two diastereoisomers of (3R, 4R) -4- [3- (R, S) -hydroxy-3 - (6-methoxyquinolin-4-yl) propyl] ] -1- [2-Cyclopentylthio) ethyl] piperidine-3-acetic acid were separated. (3R, 4R) -4- [3-Hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-3-acetic acid, diastereoisomeric B, in the form of a white solid which is the dihydrochloride salt. (aD20 = -89.6 +/- 1.6 in 0.5% ethanol), and (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) acid) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-3-acetic acid, diastereoisomer A, in the form of a thick yellow oil. (aD20 = +57.4 +/- 0.9 in 0.5% methanol). diastereoisomer A: NMR spectrum (300 MHz, (CD3) 2SO d6, δ in ppm): from 1.15 to 2.10 and from 2.25 to 2.60 (mis: 24H in all); 2.70 (mt: 2H); 3.11 (mt: 1H); 3.92 (s: 3H); 5.26 (dd, J = 8 and 4 Hz: 1H); from 7.35 to 7.45 (mt: 2H); 7.54 (d, J = 4.5Hz: 1H); 7.94 (d, J = 10 Hz: 1H); 8.71 (d, J = 4.5 Hz: 1H). diastereoisomer B: 1 H NMR spectrum (300 MHz, (CD3) 2SO d6, δ in ppm) .from 1.30 to 2.10 - from 2.15 to 2.40 and from 2.65 to 3.50 (mts : 27H in total); 4.00 and 4.01 (2s: 3H in total); 5.50 (mt: 1H); 7.54 and 7.58 (2d, J = 2.5 Hz: 1H in all); 7.71 (very broad, J = 9 Hz: 1H); 7.96 (mt: 1H); 8.23 (very broad d, J = 9 Hz: 1H); 9.00 (very broad, J - 4.5 Hz: 1H); from 9.70 to 9.85 and from 10.15 to 10.35 (2mfs: 1H in all).

Ac»de (3R,4n)-4“P-(R,S)-hydroxy-3-(6"jnéfl;oxyquinoIin-4-yI)propylJ-l-[2>(cyelopeniyIikio)éihyi]pipéndiiic-3-acédque(3R, 4n) -4- P- (R, S) -hydroxy-3- (6-fluorophenyl) -in-4-yl) propyl] -1- [2 - (cyelopenylthio) hexyl] piperidic acid acédque

Une solution de 1,6 g de dichlorhydrate de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(cyclopentylthio)éthyl]pipéridine-3-acétate deméthyle dans 30 cm3 de dioxanne, additionnée de 2,6 cm3 de soude aqueuse 5N, estagitée pendant 6 heures à une température voisine de 65°C. Après concentration souspression réduite (5 kPa) à une température voisine de 40°C du mélange réactionnel,on obtient un résidu que l’on reprend par 2 fois 30 cm3 de chloroforme et que l’onconcentre comme dans les conditions précédentes. Le résidu est purifié parchromatographie à pression atmosphérique sur une colonne de gel de silice(granulométrie 20-45μ ; diamètre 3 cm ; volume de silice 100 cm3), en éluant par unmélange de chloroforme-méthanol-ammoniaque à 28 % (12/3/0,5 en volumes), et enrecueillant des fractions de 30 cm3. Les fractions contenant le produit attendu sontréunies et concentrées comme ci-dessus. On obtient 1,5 g d’une laque incolore que 268 Π20 2 2 l’on reprend par 20 cm3 d’éther diéthylique, essore et lave par 2 fois 10 cm3 d’étherdiéthylique. Le produit est séché sous pression partielle (5 kPa), puis à poids constant,à l’étuve sous pression réduite (10 Pa) à une température voisine de 40°C. On obtient 1,35 g d’acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(cyclopentylthio)éthyI]pipéridine-3-acétique, sous forme d’un solide blanc.A solution of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) dihydrochloride (1.6 g) ) ethyl] piperidine-3-methyl acetate in 30 cm3 of dioxane, added with 2.6 cm3 of 5N aqueous sodium hydroxide, is stirred for 6 hours at a temperature of 65 ° C. After concentration under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. of the reaction mixture, a residue is obtained which is taken up in twice 30 cm 3 of chloroform and which is concentrated as in the preceding conditions. The residue is purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45 μ, diameter 3 cm, volume of silica 100 cm 3), eluting with a mixture of chloroform-methanol-ammonia at 28% (12/3 / 0.5 in volumes), and collecting fractions of 30 cm3. Fractions containing the expected product are collected and concentrated as above. 1.5 g of a colorless lacquer are obtained, which is taken up in diethyl ether (20 cc), drained and washed with twice 10 cm3 of diethyl ether. The product is dried under partial pressure (5 kPa), then at constant weight, in an oven under reduced pressure (10 Pa) at a temperature in the region of 40 ° C. 1.35 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) acid are obtained. ethylpiperidine-3-acetic acid as a white solid.

Spectre de R.M.NJH (300 MHz, (CD3)2SO d6, δ en ppm). On observe un mélange dedeux diastéréoisomères : de 1,00 à 2,20 et de 2,25 à 2,80 (mis : 25H en totalité) ; 3,10 (mt : 2H) ; 3,92 (s large:3H) ; 5,26 (mf : 1H) ; de 7,20 à 7,60 (mt : 3H) ; 7,93 (d large, J = 9 Hz : 1H) ; 8,71(mt : 1H).Spectrum of R.M.NJH (300 MHz, (CD3) 2SO d6, δ in ppm). A mixture of two diastereoisomers is observed: from 1.00 to 2.20 and from 2.25 to 2.80 (put: 25H in total); 3.10 (mt: 2H); 3.92 (brs: 3H); 5.26 (mf: 1H); from 7.20 to 7.60 (mt: 3H); 7.93 (broad d, J = 9 Hz: 1H); 8.71 (mt: 1H).

Exemple S4AExample S4A

Dichlorhydrate de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yI)propyl]-l-[2-(cyclopentylthio)éthyl]pipéridine-3-acétate de méthyle A un mélange de 2,5 g de (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(cyclopentylthio)éthyl]pipéridine-3-acétate de méthyle dans 40 cm3 de méthanoladditionnés d’une goutte de soude aqueuse 5N, on ajoute par petites fractions, en30 minutes environ, à une température inférieure à 30°C, sous agitation et sousatmosphère inerte, 0,227 g de borohydrure de sodium. Après 3 heures d’agitation dumélange réactionnel à une température voisine de 20°C, on ajoute 100 cm3 d’eau, puisl’on extrait par 4 fois 50 cm3 d’acétate d’éthyle. Les extraits réunis sont lavés par3 fois 50 cm3 d’eau, séchés sur sulfate de magnésium, filtrés, concentrés sous pressionréduite (5 kPa) à une température voisine de 40°C. L’huile résiduelle obtenue estpurifiée par chromatographie à pression atmosphérique, sur une colonne de gel desilice (granulométrie 20-45μ ; diamètre 3,2 cm ; volume de silice 100 cm3), en éluantpar de l’acétate d’éthyle pur et en recueillant des fractions de 25 cm3. Les fractionscontenant le produit attendu sont réunies, puis concentrées comme ci-dessus. Onobtient 2,1 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoIin-4-yl)propyl]-l-[2-(cyclopentylthio)éthyl]pipéridine-3-acétate de méthyle, sous forme d’une huile decouleur jaune pâle. Le chlorhydrate a été préparé de la façon suivante : une solutionde 0,5 g de l’huile obtenue ci-dessus, solubilisée dans 15 cm3 de dichlorométhane, estversée sous agitation dans 4 cm3 d’éther diéthylique chlorhydrique IN. Un produitprécipite, puis cristallise par addition de 25 cm3 d’éther diéthylique. Le, solide estfiltré, lavé par 2 fois 10 cm3 d’éther, séché sous vide potassique (5 kPa), puis à poids 120 2 2 269 constant, à l’étuve, sous pression réduite (10 Pa) à une température voisine de 40°C.On obtient 0,35 g de dichlorhydrate de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyI]-1 -[2-(cyclopentylthio)éthyl]pipéridine-3-acétate deméthyle, sous forme d’un solide de couleur blanc cassé.(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (2- (cyclopentylthio) ethyl] piperidine-3-acetate dihydrochloride To a mixture of 2.5 g of (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine 3-methyl acetate in 40 cm3 of methanoladditioned with a drop of 5N aqueous sodium hydroxide, 0.227 g of sodium borohydride are added in small portions, in approximately 30 minutes, at a temperature of less than 30.degree. C., with stirring and inert subatmosphere. . After stirring for 3 hours in the reaction mixture at a temperature in the region of 20 ° C., 100 cm3 of water are added and then the mixture is extracted with ethyl acetate (4 × 50 cc). The combined extracts are washed with 3 times 50 cm3 of water, dried over magnesium sulphate, filtered and concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. The residual oil obtained is purified by chromatography at atmospheric pressure, on a desilice gel column (particle size 20-45μ, diameter 3.2 cm, volume of silica 100 cm 3), eluting with pure ethyl acetate and collecting fractions of 25 cm3. The fractions containing the expected product are combined and then concentrated as above. 2.1 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinin-4-yl) propyl] -1- (2- (cyclopentylthio) ethyl] piperidine are obtained. -3-methyl acetate, in the form of a pale yellow oil. The hydrochloride salt was prepared in the following manner: a solution of 0.5 g of the oil obtained above, solubilized in 15 cm3 of dichloromethane, is refluxed with stirring in 4 cm3 of 1N hydrochloric diethyl ether. A product precipitated and then crystallized by addition of 25 cm3 of diethyl ether. The solid is filtered off, washed with twice 10 cm3 of ether, dried under potassium vacuum (5 kPa), then at constant weight, in an oven, under reduced pressure (10 Pa) at a temperature in the vicinity of 50.degree. 40 ° C. 0.35 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1-dihydrochloride is obtained. - (cyclopentylthio) ethyl] piperidine-3-methyl acetate, in the form of an off-white solid.

Spectre infra rouge (KBr) : 3355 ; 2950 ; 2560 ; 2051 ; 1982 ; 1731 ; 1619 ; 1601 ;1428 ; 1248 ; 1206 ; 1020 ; 849 et 714 cm·'. (3R,4R)-4-[3-Oxo-3-(6-méthoxyquinolin-4-yl)propylj-l-[2- (cyclopentylthio)éthyl]pipéridine-3-acétate de méthyleInfra red spectrum (KBr): 3355; 2950; 2560; 2051; 1982; 1731; 1619; 1601; 1428; 1248; 1206; 1020; 849 and 714 cm · '. Methyl (3R, 4R) -4- [3-Oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-3-acetate

Un mélange de 4,9 g de (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yI)propyI]pipéridine-3-acétate de méthyle, 2,9 g de (2-chloroéthyl)cyclopentyl sulfure, 9 g decarbonate de potassium et 2,7 g d’iodure de potassium dans 130 cm3 d’acétonitrile estagité pendant 17 heures à une température voisine de 65°C. Après refroidissement àune température voisine de 20°C, le mélange réactionnel est additionné de 150 cm3d’eau, extrait par 3 fois 60 cm3 d’acétate d’éthyle. Les extraits organiques sont réunis,lavés par 2 fois 50 cm3, séchés sur sulfate de magnésium, filtrés, concentrés souspression réduite (5 kPa) à une température voisine de 40°C. On obtient une huile quel'on purifie par chromatographie à pression atmosphérique sur une colonne de gel desilice (granulométrie 20-45μ ; diamètre 4 cm ; volume de silice 300 cm3), en éluantpar de l’acétate d’éthyle pur et en recueillant des fractions de 70 cm3 environ. Lesfractions contenant le produit attendu sont réunie, puis concentrées dans lesconditions de ci-dcssus. On obiitnt 2,6 g de (3Ri4R)-4-[3-oxo-3-(6-méthoxyquinolin- 4-yl)propyl]-l-[2-(cyc}opentylthÎo)ôthyl]pipéridiiie-3-acéiate de méthyle, sous formed’une huile de couleur jaune.A mixture of 4.9 g of methyl (3R, 4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetate, 2.9 g of (2- chloroethyl) cyclopentyl sulfide, 9 g of potassium decarbonate and 2.7 g of potassium iodide in 130 cm3 of acetonitrile are stirred for 17 hours at a temperature of 65 ° C. After cooling to a temperature in the region of 20 ° C., 150 cm3 of water are added to the reaction mixture and the mixture is extracted with ethyl acetate (3 × 60 cc). The organic extracts are combined, washed twice with 50 cm3, dried over magnesium sulphate, filtered and concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. An oil is obtained which is purified by chromatography at atmospheric pressure on a column of desilic gel (particle size 20-45μ, diameter 4 cm, volume of silica 300 cm 3), eluting with pure ethyl acetate and collecting fractions of about 70 cm3. Fractions containing the expected product are pooled and then concentrated in the above conditions. 2.6 g of (3Ri4R) -4- [3-oxo-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclo) opentylthio) ethyl] piperidin-3-aceate are obtained. methyl, in the form of a yellow oil.

Spectre infra rouge (CC14) : 2952 ; 2802 ; 1738 ; 1692 ; 1620 ; 1504 ; 1242 ; 1165 ;1032 et 850 cm'1Infrared spectrum (CCl4): 2952; 2802; 1738; 1692; 1620; 1504; 1242; 1165, 1032 and 850 cm -1

Le (3R,4R)-4-[3-oxo-3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-acétate deméthyle a été obtenu dans l’exemple 48.(3R, 4R) -4- [3-Oxo-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-methyl acetate was obtained in Example 48.

Le 2-chloroéthylcyclopentyl sulfure peut être préparé par application de la méthodedécrite dans la demande de brevet FR 2 395 260.The 2-chloroethylcyclopentyl sulfide can be prepared by application of the method described in the patent application FR 2,395,260.

Exemple 55 120 2 2 270Example 55 120 2 2 270

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyIJ-l-(3-(2,6-difluorophényI)prop-2-ynyI]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (3- (2,6-difluorophenyl) prop-2-yl) acid ] piperidine-3-carboxylic acid

Une solution de 0,531 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-!-[3-(2,6-difluorophényl)prop-2-ynyl]pipéridine-3-carboxylate de méthyledans 5,3 cm3 de dioxanne additionnés de 0,84 cm3 de soude aqueuse 5N est agitéependant 15 heures à une température voisine de 60°C. Après refroidissement à unetempérature voisine de 20°C, le mélange réactionnel est concentré sous pressionréduite (5 kPa) à une température voisine de 40°C. Le résidu obtenu est purifié parchromatographie sous une pression de 50 kPa d’azote, sur une colonne de gel de silice(granulométrie 20-45μ ; diamètre 3 cm ; 20 g), en éluant par un mélange dedichlorométhane-méthanol (90/10 en volumes) et en recueillant d’abord une fractionde 100 cm3, puis des fractions de 25 cm3. Les fractions 1 à 12 sont réunies, puisconcentrées comme précédemment. On obtient une meringue que l’on reprend sousagitation dans 15 cm3 d’éther diisopropylique pendant 15 minutes. Après addition de15 cm3 de pentane et une agitation supplémentaire de 10 minutes, le produit cristalliséformé est filtré, lavé par 2 fois 10 cm3 d’un mélange éther diisopropylique-pentane(50/50 en volumes), puis 3 fois 20 cm3 de pentane, séché à l’air. On obtient 0,293 gd’acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,6-difluorophényl)prop-2-ynyl]pipéridine-3-carboxylique, sous forme d’un solide decouleur crème fondant à 107°C.A solution of 0.531 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] - [3- (2,6-difluorophenyl) ) Methyl prop-2-ynyl] piperidine-3-carboxylate in 5.3 cm3 of dioxane supplemented with 0.84 cm3 of 5N aqueous sodium hydroxide is stirred for 15 hours at a temperature in the region of 60 ° C. After cooling to a temperature in the region of 20 ° C., the reaction mixture is concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. The residue obtained is purified by chromatography under a pressure of 50 kPa of nitrogen, on a column of silica gel (particle size 20-45 μ, diameter 3 cm, 20 g), eluting with a dichloromethane-methanol mixture (90:10). volumes) and first collecting a 100 cm3 fraction and then 25 cm3 fractions. Fractions 1 to 12 are combined, puisconcentrées as previously. A meringue is obtained which is subactivated in 15 cm3 of diisopropyl ether for 15 minutes. After addition of 15 cm3 of pentane and further stirring for 10 minutes, the crystallized product is filtered, washed with twice 10 cm 3 of a diisopropyl ether-pentane mixture (50/50 by volume), then 3 times 20 cm 3 of pentane, air dried. 0.293 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl) acid are obtained. ) prop-2-ynyl] piperidine-3-carboxylic acid, as a cream-colored solid melting at 107 ° C.

Spectre de R.M.N.^H (300 MHz, (CD3)2SO d6, δ en ppm). On observe un mélange dedeux diastéréoisomères : de 1,40 à 1,95 et de 2,30 à 3,00 (mis : 12H en totalité) ; 3,67 et 3,68 (2s : 2H entotalité) ; 3,88 et 3,92 (2s : 3H en totalité) ; 5,24 (mt : 1H) ; 5,55 (mf : 1H) ; 7,22 (mt :2H) ; de 7,30 à 7,60 (mt : 4H) ; 7,93 (d, J = 9 Hz : 1H) ; 8,70 (mt : 1H) ; de 12,20 à 12,80 (mf étalé : 1H). (3R,4R)-4-[3-(R,S)-Hydroxy-3-(6-méthoxyquinolin-4-yI) propyI]-l-[3-(2,6- difIuorophényl)prop-2-ynylÎpipéridine-3-carboxyIate de méthyleNMR spectrum (300 MHz, (CD3) 2SO d6, δ in ppm). A mixture of two diastereoisomers is observed: from 1.40 to 1.95 and from 2.30 to 3.00 (put: 12H in total); 3.67 and 3.68 (2s: 2H entotality); 3.88 and 3.92 (2s: 3H in total); 5.24 (mt: 1H); 5.55 (mf: 1H); 7.22 (mt: 2H); from 7.30 to 7.60 (mt: 4H); 7.93 (d, J = 9 Hz: 1H); 8.70 (mt: 1H); from 12.20 to 12.80 (mf spread: 1H). (3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl) prop-2-ynyl) piperidine Methyl 3-carboxyIate

Un mélange de 1,07 g de (3R,4R)-4-(3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yI)propyl]-l-(prop-2-ynyl)pipéridine-3-carboxyiate de méthyle dans 10 cm3 detriéthylamine est agité pendant 5 minutes sous atmosphère inerte à une températurevoisine de 20°C. On ajoute 0,156 g de tétrakis triphénylphosphine palladium, 0,051 gd’iodure cuivreux et 0,78 g de 1 -bromo-2,6-difluorobenzène. Le mélange est agité 120 2 2 271 pendant 3 heures 30 minutes à une température voisine de 80°C. Aprèsrefroidissement à environ 20°C, le mélange réactionnel est additionné de 30 cm3d’acétate d’éthyle et 30 cm3 d’eau. Après 10 minutes d’agitation, le mélange estdécanté. Après séparation de la phase organique, la couche aqueuse est extraite par 5 2 fois 30 cm3 d’acétate d’éthyle. Les extraits organiques sont réunis, lavés par 3 fois 30 cm3 d’eau, séchés sur sulfate de sodium, filtrés, concentrés sous pression réduite(5 kPa) à une température voisine de 40°C. Le résidu obtenu est purifié parchromatographie sous une pression d’azote de 50 kPa, sur une colonne de gel de silice(granulométrie 20-45μ ; diamètre 3 cm ; 50 g), en éluant par de l’acétate d’éthyle pur 10 et en recueillant d’abord une fraction de 300 cm3, puis des fractions de 38 cm3. Lesfractions 6 à 16 sont réunies, concentrées comme ci-dessus. On obtient 0,55 g de(3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,6-difluorophényl)prop-2-ynyl]pipéridine-3-carboxylate de méthyle, sous forme d’unemeringue de couleur jaune pâle. 15 Spectre infra rouge (CC14) :3615 ; 2950 ; 1738 ; 1622 ; 1470 ; 1241 ; 1007 ; 854 et719 cm’'A mixture of 1.07 g of (3R, 4R) -4- (3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) Piperidine-3-methyl carboxyate in 10 cm 3 of triethylamine is stirred for 5 minutes under an inert atmosphere at a temperature of 20 ° C. 0.156 g of tetrakis triphenylphosphine palladium, 0.051 g of cuprous iodide and 0.78 g of 1-bromo are added. -2.6-Difluorobenzene The mixture is stirred for 3 hours 30 minutes at a temperature in the region of 80 ° C. After cooling to about 20 ° C., 30 cm3 of ethyl acetate are added to the reaction mixture. 30 cm3 of water After 10 minutes of stirring, the mixture is decanted After separation of the organic phase, the aqueous layer is extracted with 2 times 30 cm 3 of ethyl acetate The organic extracts are combined, washed with 3 times 30 cm3 of water, dried over sodium sulphate, filtered, concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. the residue obtained is purified by chromatography under a nitrogen pressure of 50 kPa, on a silica gel column (particle size 20-45 μ; diameter 3 cm; 50 g), eluting with pure ethyl acetate and first collecting a 300 cc fraction and then 38 cc fractions. Fractions 6 to 16 are united, concentrated as above. 0.55 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- difluorophenyl) prop-2-ynyl] piperidine-3-carboxylic acid methyl ester as a pale yellow emeryl. Infra red spectrum (CCl4): 3615; 2950; 1738; 1622; 1470; 1241; 1007; 854 and 719 cm ''

Le (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propylj-1 -(prop-2-ynyl)pipéridine-3-carboxylate de méthyle peut être préparé comme décrit dansl’exemple 32. 20 Exemple. 56Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-carboxylate may be prepared as described in Example 32. Example. 56

Acide (3R/R)'z!-f3-(o-m<itIioxj'quinoHn-4-yl)propylj-l-[3-(3,5-difluorophényl)piOp-2-ynyl3pipéridine-3-acétique A une solution de 0,525 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yI)propyl]-l-[3-(3,5-difluorophényl)prop-2-ynyl]pipéridine-3-acétate de méthyle dans 5 cm3 de 25 dioxanne, on introduit sous agitation, à une température voisine de 20°C, 0,83 cm3 desoude aqueuse 5N, puis le mélange est chauffé pendant 3 heures à une températurevoisine de 60°C. Après refroidissement à environ 20°C, le mélange est agité pendant3 jours, puis concentré sous pression réduite (5 kPa) à une température voisine de40°C. Le résidu obtenu est repris par 15 cm3 d’eau, puis la solution est extraite par 30 5 cm3 d’acétate d’éthyle. La phase aqueuse est amenée à pH voisin de 5-6 par addition de 4,1 cm3 d’acide chlorhydrique aqueux IN, puis extraite d’abord par 30 cm3 de dichlorométhane, puis 10 cm3 du même solvant. Les extraits organiques sont réunis, lavés par 2 fois 5 cm3 d’eau, séchés sur sulfate de magnésium, filtrés, concentrés sous 272 12022’ pression réduite (5 kPa) à une température voisine de 40°C. Le résidu obtenu estrepris dans de l’éther diéthylique, puis concentré dans les mêmes conditions queprécédemment jusqu'à obtention d’un poids constant. On obtient 0,45 g d’acide(3R,4R)-4-[3-(6-méthoxyquinoîin-4-yl)propyl]-l-[3-(3,5-difluoro-phényl)prop-2- 5 ynyl]pipéridine-3-acétique, sous forme d’un solide de couleur beige clair.(3R / R) 3- (3- (3,5-difluorophenyl) p -Pol-2-ynyl) -piperidine-3-acetic acid-3-yl) propyl] -1- [3- (3,5-difluorophenyl) pIp-2-yl) piperidine-3-acetic acid solution; 0.525 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenyl) prop-2-ynyl] piperidine-3-acetate In 5 cm3 of dioxane, the mixture is stirred at a temperature in the region of 20 ° C. and 0.83 cm 3 of 5N aqueous solution are added. The mixture is then heated for 3 hours at a temperature of about 60.degree. After cooling to about 20 ° C, the mixture is stirred for 3 days and then concentrated under reduced pressure (5 kPa) at a temperature of 40 ° C. The residue obtained is taken up in 15 cm3 of water and the solution is extracted with 5 cm3 of ethyl acetate. The aqueous phase is brought to a pH of about 5-6 by addition of 4.1 cm 3 of 1 N aqueous hydrochloric acid, then extracted firstly with 30 cm 3 of dichloromethane and then 10 cm 3 of the same solvent. The organic extracts are combined, washed with 2 times 5 cm3 of water, dried over magnesium sulphate, filtered and concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. The residue obtained is taken up in diethyl ether and then concentrated under the same conditions as previously until a constant weight is obtained. 0.45 g of (3R, 4R) -4- [3- (6-methoxyquinin-4-yl) propyl] -1- [3- (3,5-difluoro-phenyl) prop-2-yl) acid is obtained. 5-yl] piperidine-3-acetic acid as a light beige solid.

Spectre de R.M.NJH (300 MHz, (CD3)2SO d6, δ en ppm) : de 1,20 à 1,80 (mi : 7H) ;de 2,10 à 2,35 (mt : 4H) ; 2,43 (dd, J = 16,5 et 10,5 Hz : 1H) ; 2,75 (mt : 2H) ; 3,05(mt : 2H) ; 3,47 (s : 2H) ; 3,93 (s : 3H) ; 7,18 (mt : 2H) ; de 7,25 à 7,35 (mt : 1H) ; 7,33 (d, J = 4 Hz : 1H) ; de 7,35 à 7,45 (mt : 2H) ; 7,92 (d, J = 9 Hz : 1H) ; 8,62 (d, J = 10 4 Hz : 1H). (3R,4R)-4-[3-(6-Méthoxyquinolin-4-yl)propyI]-l-[3-(3j5-difIuorophényl)prop-2-ynyl]pipéridine-3-acétate de méthyle A un mélange agité de 0,77 g de (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(prop-2-ynyl)pipéridine-3-acétate de méthyle dans 7,7 cm3 de triéthylamine, on ajoute 15 à une température voisine de 20°C, sous atmosphère inerte, 0,35 cm3 de l-bromo-3,5-difluorobenzène, puis 0,112 g de tétrakis triphénylphosphine palladium et 0,037 gd’iodure cuivreux. La suspension obtenue est chauffée à une température voisine de80°C pendant 3 heures, puis concentrée sous pression réduite (5 kPa) à unetempérature voisine de 40°C. Le résidu obtenu est repris par 50 cm3 d’acétate d’éthyle 20 et 20 cm3 d’eau. Après agitation du mélange pendant 15 minutes, l’insoluble. persistant est filtré sur clarcel, puis le filtrat est décanté : la phase organique estséparée, puis lavée par 3 fois 3 cm3 d’eau, une solution aqueuse saturée de chlorure desodium, séchée sur sulfate de magnésium, filtrée, concentrée sous pression réduite (5kPa) à une température voisine de 40°C. Le résidu huileux obtenu est purifié par 25 chromatographie sous une pression d’azote de 50 kPa, sur une colonne de gel de silice(granulométrie 40-63μ ; diamètre 3 cm ; 45 g) en éîuant par un mélange dedichlorométhane-méthanol (97/3 en volumes). On recueille les fractions contenant leproduit attendu. Celles-ci sont concentrées sous pression réduite (5 kPa) à unetempérature voisine de 40°C. On obtient 0,345 g de (3R,4R)-4-[3-(6- 30 méthoxyquinolin-4-yI)propyl)-l-[3-(3,5-difluorophényl)prop-2-ynyl]pipéridine-3-acétate de méthyle, sous forme d’une huile de couleur jaune pâle.R.M.NJH spectrum (300 MHz, (CD3) 2SO d6, δ in ppm): 1.20 to 1.80 (m.h: 7H), 2.10 to 2.35 (mt: 4H); 2.43 (dd, J = 16.5 and 10.5 Hz: 1H); 2.75 (mt: 2H); 3.05 (mt: 2H); 3.47 (s: 2H); 3.93 (s: 3H); 7.18 (mt: 2H); from 7.25 to 7.35 (mt: 1H); 7.33 (d, J = 4 Hz: 1H); from 7.35 to 7.45 (mt: 2H); 7.92 (d, J = 9 Hz: 1H); 8.62 (d, J = 10 4 Hz: 1H). (3R, 4R) -4- [3- (6-Methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenyl) prop-2-ynyl] piperidine-3-methyl acetate To a stirred mixture 0.77 g of methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-acetate in 7.7 cc of triethylamine, 0.35 cm3 of 1-bromo-3,5-difluorobenzene and then 0.112 g of tetrakis triphenylphosphine palladium and 0.037 g of cuprous iodide are added at a temperature in the region of 20 ° C. under an inert atmosphere. The suspension obtained is heated at a temperature of 80 ° C for 3 hours and then concentrated under reduced pressure (5 kPa) at a temperature of 40 ° C. The residue obtained is taken up in 50 cm3 of ethyl acetate and 20 cm3 of water. After stirring the mixture for 15 minutes, the insoluble. persistant is filtered on clarcel, then the filtrate is decanted: the organic phase is separated, then washed with 3 times 3 cm3 of water, a saturated aqueous solution of sodium chloride, dried over magnesium sulfate, filtered, concentrated under reduced pressure (5 kPa ) at a temperature of 40 ° C. The oily residue obtained is purified by chromatography under a nitrogen pressure of 50 kPa, on a column of silica gel (particle size 40-63 μ, diameter 3 cm, 45 g), eluting with a dichloromethane-methanol mixture (97 / 3 in volumes). Fractions containing the expected product are collected. These are concentrated under reduced pressure (5 kPa) at a temperature of 40 ° C. 0.345 g of (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl) -1- [3- (3,5-difluorophenyl) prop-2-ynyl] piperidine-3 are obtained. methyl acetate, in the form of a pale yellow oil.

Spectre de masse (El) m/z=5O6 M+ 120 2 2 273Mass Spectrum (EI) m / z = 5O6 M + 120 2 2 273

Le (3R,4R)-4-[3-(6-méthoxyquinolin-4-yl)propyl]-l-(prop-2-ynyl)pipéridine-3-acétate de méthyle a été préparé selon le mode opératoire décrit dans l’exemple 39.Methyl (3R, 4R) -4- [3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-acetate was prepared according to the procedure described in US Pat. Example 39

Exemple 57Example 57

Dichlorhydrate de l’acide (3R,4R)-l-[2-(3,5-difluorophénylthio)éthyl]-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yI)propyI]pipéridine-3-carboxylique A une solution de 0,42 g de (3R,4R)-l-[2-(3,5-difIuorophénylthio)éthyl]-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-carboxylate de méthyle dans 5.5 cm3 de méthanol, on ajoute sous agitation et sous atmosphère inerte, à unetempérature voisine de 20°C, 1,6 cm3 d’une solution aqueuse de soude 5N. Lemélange est chauffé pendant 16 heures à une température voisine de 60°C. Lasolution obtenue est évaporée sous pression réduite (5 kPa) à une température voisinede 40°C, puis au résidu obtenu on ajoute 5 cm3 d’eau distillée et 2,66 cm3 d’acidechlorhydrique aqueux 6N. Le mélange est alors chauffé au voisinage de 60°C jusqu’àl’obtention d’une solution homogène que l’on évapore ensuite dans les conditions deci-dessus. Le résidu obtenu est trituré dans 10 cm3 d’un mélange de dichlorométhane-méthanol (90/10 en volumes), puis l’insoluble résultant est filtré, lavé par 2 fois 2.5 cm3 de ce même mélange. Le filtrat est concentré dans les mêmes conditions queprécédemment. On obtient 0,465 g de dichlorhydrate de l’acide (3R,4R)-l-[2-(3,5-difluorophénylthio)éthyl]-4-[3-(R5S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]pipéridme-3-carboxyb’que, sous forme d’une meringue de couleur jaune fondant à160°C en se décomposant.(3R, 4R) -1- [2- (3,5-Difluorophenylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) dihydrochloride propyl] piperidine-3-carboxylic acid To a solution of 0.42 g of (3R, 4R) -1- [2- (3,5-difluorophenylthio) ethyl] -4- [3- (R, S) -hydroxy) Methyl 3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate in 5.5 cm 3 of methanol is added with stirring and under an inert atmosphere, at a temperature in the region of 20 ° C., 1.6 cm 3 of 5N aqueous sodium hydroxide solution. The mixture is heated for 16 hours at a temperature of 60 ° C. The solution obtained is evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. and then to the residue obtained is added 5 cm 3 of distilled water and 2.66 cm 3 of 6 N aqueous hydrochloric acid. The mixture is then heated to around 60 ° C. until a homogeneous solution is obtained which is then evaporated under the above conditions. The residue obtained is triturated in 10 cm3 of a mixture of dichloromethane-methanol (90/10 by volume), then the resulting insoluble matter is filtered, washed twice with 2.5 cm3 of this same mixture. The filtrate is concentrated under the same conditions as previously. 0.465 g of (3R, 4R) -1- [2- (3,5-difluorophenylthio) ethyl] -4- [3- (R5S) -hydroxy-3- (6-methoxyquinolin-4) dihydrochloride is obtained. -yl) propyl] -3-piperidinecarboxylic acid, in the form of a yellow meringue melting at 160 ° C decompose.

Spectre de R.M.NJH (300 MHz, (CD3)2SO d6, δ en ppm). On observe un mélange dedeux diastéréoisomères : de 1,35 à 2,35 et de 2,60 à 4,00 (mts : 16H en totalité) ; 4,01 et 4,02 (2s : 3H entotalité) ; de 5,45 à 5,65 (mt : 1H) ; 7,10 (mt : 1H) ; 7,21 (mt : 2H) ; de 7,50 à 7,70(mt : 1H) ; 7,76 (mt : 1H) ; 8,00 (mt : 1H) ; 8,33 (mt : 1H) ; 9,04 (d, J = 5,5 Hz :1H) ; de 11,10 à 11,55 (2mfs : 1H en totalité). (3R,4R)-l-[2-(3,5-Difluorophénylthio)éthyl]-4-[3-(R,S)-hydroxy-3-(6- méthoxyquinolin-4-yl)propyl]pipéridine-3-carboxylate de méthyle A une solution de 0,717 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]pipéridine-3-carboxylate de méthyle dans 15 cm3 d’acétonitrile et 1 cm3 de 274 120 2 2 méthanol, on ajoute sous agitation et sous atmosphère inerte, à une températurevoisine de 20°C, 0,332 g de carbonate de potassium puis 0,4 g d’iodure de potassiumet enfin 0,675 g de l-[(2-bromoéthyl)thio]-3,5-difluorobenzène préalablementsolubilisé dans 5 cm3 d’acétonitrile. Le mélange est chauffé pendant 3 heures à unetempérature voisine de 80°C. Après refroidissement à une température voisine de20°C, le mélange réactionnel est filtré, le gâteau lavé par 2 fois 5 cm3 d’acétonitrile.Le filtrat est évaporé sous pression réduite (5 kPa) à une température voisine de 40°C.Le résidu obtenu est purifié par chromatographie sous une pression de 50 kPa d’azote,sur une colonne de gel de silice (granulométrie 40-63μ ; diamètre 3,5 cm ; hauteur35 cm), en éluant par un mélange de dichlorométhane-méthanol (95/5 en volumes) eten recueillant des fractions de 35 cm3. Les fractions 18 à 21 sont réunies puisévaporées comme ci-dessus. On obtient 0,47 g de (3R,4R)-l-[2-(3,5-difluorophényl-thio)éthyl]-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl] pipéridine-3-carboxylate de méthyle, sous forme d’une huile visqueuse de couleur jaune orangé.Spectrum of R.M.NJH (300 MHz, (CD3) 2SO d6, δ in ppm). A mixture of two diastereoisomers is observed: from 1.35 to 2.35 and from 2.60 to 4.00 (mts: 16H in total); 4.01 and 4.02 (2s: 3H entotality); from 5.45 to 5.65 (mt: 1H); 7.10 (mt: 1H); 7.21 (mt: 2H); from 7.50 to 7.70 (mt: 1H); 7.76 (mt: 1H); 8.00 (mt: 1H); 8.33 (mt: 1H); 9.04 (d, J = 5.5 Hz: 1H); from 11.10 to 11.55 (2mfs: 1H in total). (3R, 4R) -1- [2- (3,5-Difluorophenylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3 Methylcarboxylate To a solution of 0.717 g of methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-carboxylate in 15 cm3 of acetonitrile and 1 cm3 of 274 120 2 2 methanol, 0.332 g of potassium carbonate and 0.4 g of potassium iodide are finally added under stirring and under an inert atmosphere at a temperature of 20 ° C. 0.675 g of 1 - [(2-bromoethyl) thio] -3,5-difluorobenzene previously solubilized in 5 cm3 of acetonitrile. The mixture is heated for 3 hours at a temperature of about 80 ° C. After cooling to a temperature in the region of 20 ° C., the reaction mixture is filtered and the cake washed with twice 5 cm 3 of acetonitrile. The filtrate is evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. obtained is purified by chromatography under a pressure of 50 kPa of nitrogen, on a column of silica gel (particle size 40-63μ, diameter 3.5 cm, height 35 cm), eluting with a mixture of dichloromethane-methanol (95 / In volumes) and collecting 35 cm3 fractions. Fractions 18 to 21 are combined and evaporated as above. 0.47 g of (3R, 4R) -1- [2- (3,5-difluorophenylthio) ethyl] -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin)) are obtained. Methyl 4-yl) propyl] piperidine-3-carboxylate as an orange-yellow viscous oil.

Spectre infra rouge (CHjCIJ : 3597 ; 2951 ; 2814 ; 1733 ; 1611 ; 1586 ; 1242 ; 1119 ;985 ; 877 ; 840 et 667 cm-1 l-[(2-BromoéthyI)thio]-3,5-difluorobenzène A un mélange de 7,5 g de 3,5-difluorothiophénol dans 9,01 cm3 de 1,2-dibromo-éthane maintenu à une température voisine de 23°C, on ajoute sous agitation et sousatmosphère inerte, une solution de 2,59 g de soude en pastille dans 27 cm3 d’eaudistillée, puis 0,27 cm3 d’aliquat 336 (tricaprylylméthylammonium chlorure). Après15 minutes d’agitation à une température voisine de 20°C, on ajoute au mélange50 cm3 de dichlorométhane, puis au bout de quelques minutes la phase organique estdécantée, lavée par 25 cm3 d’eau, 25 cm3 d’une solution saturée de chlorure desodium à 10 %, séchée sur sulfate de magnésium, filtrée, évaporée sous pressionréduite (5 kPa) à une température voisine de 40°C. Le résidu d’évaporation est purifiépar chromatographie sous une pression d’azote de 50 kPa, sur une colonne de gel desilice (granulométrie 40-63μ ; diamètre 5 cm ; hauteur 30 cm) en éluant par ducyclohexane et en recueillant d’abord une fraction de 500 cm3, puis des fractions de50 cm3. Les fractions 9 à 26 sont réunies puis concentrées sous pression réduite(5 kPa) à une température voisine de 40°C. On obtient 5,9 g de l-[(2-bromoéthyl)thio]-3,5-difluorobenzène, sous forme d’un liquide incolore. \ 120 2 2 275Infra red spectrum (CH 2 Cl 2: 3597; 2951; 2814; 1733; 1611; 1586; 1242; 1119; 985; 877; 840; and 667 cm -1; 1 - [(2-Bromoethyl) thio] -3,5-difluorobenzene; mixture of 7.5 g of 3,5-difluorothiophenol in 9.01 cm3 of 1,2-dibromoethane maintained at a temperature in the region of 23 ° C., a 2.59 g solution is added with stirring and inert under-atmosphere. sodium hydroxide in pellet in 27 cm3 of water, then 0.27 cm3 of aliquat 336 (tricaprylylmethylammonium chloride) After stirring for 15 minutes at a temperature in the region of 20 ° C, 50 cm3 of dichloromethane are added to the mixture and then a few minutes the organic phase is decanted, washed with 25 cm3 of water, 25 cm3 of a saturated solution of 10% sodium chloride, dried over magnesium sulfate, filtered, evaporated under reduced pressure (5 kPa) at a temperature of 40 ° C. The evaporation residue is purified by chromatography under a nitrogen pressure of 50 kPa, on a gel deilice (particle size 40-63μ, diameter 5 cm; height 30 cm) eluting with cyclohexane and first collecting a fraction of 500 cm3, then fractions of 50 cm3. Fractions 9 to 26 are combined and then concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 5.9 g of 1 - [(2-bromoethyl) thio] -3,5-difluorobenzene are obtained in the form of a colorless liquid. \ 120 2 2 275

Spectre infra rouge (CC14) : 3094 ; 1607 ; 1587 ; 1429 ; 1192 ; 1122 ; 988 ; 876 ; 841et 667 cm'1Infrared spectrum (CCl4): 3094; 1607; 1587; 1429; 1192; 1122; 988; 876; 841and 667 cm'1

Le 3,5-difluorothiophénol peut être préparé selon DAE-KEE KIM ; JONGSIK GAMet col. J. Med. Chem., 1997 p. 23713,5-difluorothiophenol can be prepared according to DAE-KEE KIM; JONGSIK GAMet collar J. Med. Chem., 1997 p. 2371

Exemple 58Example 58

Acide (3R,4R)-4-(3-(R,S)-hydroxy-3-(6-méthoxyquinolm-4-yl)propyI]-l-[3-(2,3-difluorophényI)prop-2-ynyI]pipéridine-3-carboxylique(3R, 4R) -4- (3- (R, S) -hydroxy-3- (6-methoxyquinol-4-yl) propyl] -1- [3- (2,3-difluorophenyl) prop-2- acid ynyI] -piperidine-3-carboxylic acid

Un mélange de 0,810 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyqumolin-4-yl)propyl]-l-[3-(2,3-difluorophényl)prop-2-ynyl]pipéridine-3-carboxylate de méthyledans 8 cm3 de dioxanne additionnés de 1,3 cm3 de soude aqueuse 5N est agité pendant17 heures à une température voisine de 60°C. Après refroidissement aux environs de20°C, le mélange réactionnel est évaporé sous pression réduite (5 kPa), à unetempérature voisine de 50°C. Le résidu obtenu est purifié par chromatographie, sousune pression de 50 kPa d’azote, sur une colonne de gel de silice (granulométrie 20-45μ ; diamètre 3 cm ; masse 45 g) en éluant par un mélange de dichlorométhane-méthanol (92/8 en volumes). On recueille d’abord une fraction de 275 cm3, puis desfractions de 20 cm3. On recueille les fractions 12 à 46. Celles-ci sont réunies,concentrées sous pression réduite (5 kPa) à une température voisine de 35°C. Lerésidu obtenu est repris dans le dichlorométhane, filtré. Le filtrat est évaporé commeprécédemment, puis le nouveau résidu obtenu est trituré dans 10 cm3 d’étherdiisopropylique. Le mélange est agité pendant 1 heure à une température voisine de20°C, puis abandonné pendant 16 heures. Le précipité solide est séparé par filtration,lavé par 2 fois 10 cm3 du même solvant, puis par 2 fois 10 cm3 de pentane. On obtient0,47 g d’acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,3-difluorophényl)prop-2-ynyl]pipéridine-3-carboxyIique, sous forme d’un solide decouleur blanche, fondant à 92°C.A mixture of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyqumolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl), 0.810 g. ) Methyl prop-2-ynyl] piperidine-3-carboxylate in 8 cm 3 of dioxane supplemented with 1.3 cm 3 of 5N aqueous sodium hydroxide is stirred for 17 hours at a temperature in the region of 60 ° C. After cooling to about 20 ° C., the reaction mixture is evaporated under reduced pressure (5 kPa) at a temperature of about 50 ° C. The residue obtained is purified by chromatography, under a pressure of 50 kPa of nitrogen, on a column of silica gel (particle size 20-45μ, diameter 3 cm, mass 45 g), eluting with a mixture of dichloromethane-methanol (92 / 8 in volumes). First a fraction of 275 cm3 is collected, then fractions of 20 cm3. Fractions 12 to 46 are collected. These are combined and concentrated under reduced pressure (5 kPa) at a temperature in the region of 35 ° C. The residue obtained is taken up in dichloromethane, filtered. The filtrate is evaporated as before, and the new residue obtained is triturated in 10 cm3 of diisopropyl ether. The mixture is stirred for 1 hour at a temperature of 20 ° C and then left for 16 hours. The solid precipitate is separated by filtration, washed with 2 times 10 cm 3 of the same solvent and then with 2 times 10 cm 3 of pentane. 0.47 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3) -acidic acid is obtained. difluorophenyl) prop-2-ynyl] piperidine-3-carboxylic acid, as a white-colored solid, melting at 92 ° C.

Spectre de R.M.N. lH (300 MHz, (CD3)2SO d6, δ en ppm) : on observe un mélange dediastéréo isomères : de 1,40 à 1,95 et de 2,30 à 3,00 (2 séries de mts : 12H en totalité) ; 3,64 et 3,65 (2s :2H en totalité) ; 3,90 et 3,92 (2s : 3H en totalité) ; 5,25 (mt : 1H) ; 5,52 (mf : 1H) ; de 7,15 à 7,30 (mt : 1H) ; de 7,30 à 7,60 (mt : 5H) ; 7,93 (d, J = 10 Hz : 1H) ; 8,70 (d, J = 4,5 Hz : 1H) ; de 11,90 à 12,80 (mf très étalé : 1H). 120 2 2 276 (3R,4R)-4-[3-(R,S)-Hydroxy-3-(6-méthoxyquinolin~4-yi)propyl]-l-[3-(2,3-difiuorophényI)prop-2-ynyl]pipéridine-3-carboxylate de méthyle A un mélange de 1,1 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-(prop-2-ynyl)pipéridine-3-carboxylate de méthyle dans 11 cm3 de 5 triéthylamine, agité à une température voisine de 20°C sous atmosphère inerte, onajoute 0,16 g de tétrakis triphénylphosphine palladium, 0,053 g d’iodure cuivreux et0,47 cm3 de l-bromo-2,3-difluorobenzène. Le mélange est chauffé à une températurevoisine de 80°C pendant 3 heures 30 minutes. Après refroidissement à environ 20°C,le mélange réactionnel est repris par 30 cm3 d’acétate d’éthyle et 30 cm3 d’eau, agité 10 pendant 15 minutes. La phase organique est décantée tandis que la couche aqueuse estextraite par 3 fois 30 cm3 d’acétate d’éthyle. Les extraits organiques sont réunis, lavéspar 3 fois 30 cm3 d’eau, séchés sur sulfate de sodium, filtrés, concentrés sous pressionréduite (5 kPa) à une température voisine de 40°C. Le résidu obtenu est purifié parchromatographie sous une pression d’azote de 50 kPa, sur une colonne de gel de silice 15 (granulométrie 20-45μ ; diamètre 3 cm ; 50 g) en éluant par de l’acétate d’éthyle pur.On recueille d’abord 1 fraction de 300 cm3, puis on effectue des fractions de 30 cm3.Les fractions 10 à 30 sont réunies, évaporées dans les conditions de ci-dessus. Onobtient 0,94 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxy-quinolin-4-yl)propyl]-l-[3-(2,3-difluorophényl)prop-2-ynyl]pipéridine-3-carboxylate de méthyle, sous forme 20 d’une meringue de couleur orangée.Spectrum of R.M.N. 1H (300 MHz, (CD3) 2SO d6, δ in ppm): a mixture of diastereomeric isomers is observed: from 1.40 to 1.95 and from 2.30 to 3.00 (2 series of mts: 12H in total) ; 3.64 and 3.65 (2s: 2H in total); 3.90 and 3.92 (2s: 3H in total); 5.25 (mt: 1H); 5.52 (mf: 1H); from 7.15 to 7.30 (mt: 1H); from 7.30 to 7.60 (mt: 5H); 7.93 (d, J = 10 Hz: 1H); 8.70 (d, J = 4.5 Hz: 1H); from 11.90 to 12.80 (mf very spread: 1H). 120 2 276 (3R, 4R) -4- [3- (R, S) -Hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl) prop) Methyl 2-ynyl] piperidine-3-carboxylate To a mixture of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl)) ) propyl] -1- (prop-2-ynyl) piperidine-3-carboxylic acid methyl ester in 11 cm3 of triethylamine, stirred at a temperature of 20 ° C under an inert atmosphere, 0.16 g of tetrakis triphenylphosphine palladium, 0.053 g of cuprous iodide and 0.47 cm3 of 1-bromo-2,3-difluorobenzene. The mixture is heated to a temperature of about 80 ° C for 3 hours 30 minutes. After cooling to about 20 ° C, the reaction mixture is taken up in 30 cm3 of ethyl acetate and 30 cm3 of water, stirred for 15 minutes. The organic phase is decanted while the aqueous layer isextracted with 3 times 30 cm3 of ethyl acetate. The organic extracts are combined, washed with 3 times 30 cm3 of water, dried over sodium sulphate, filtered and concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. The residue obtained is purified by chromatography under a nitrogen pressure of 50 kPa, on a column of silica gel (particle size 20-45 μ, diameter 3 cm, 50 g), eluting with pure ethyl acetate. first collects 1 fraction of 300 cm3, then fractions of 30 cm3 are carried out. Fractions 10 to 30 are combined, evaporated under the conditions of above. 0.94 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxy-quinolin-4-yl) propyl] -1- [3- (2,3 g) are obtained. Methyl (difluorophenyl) prop-2-ynyl] piperidine-3-carboxylate, as an orange meringue.

Spectre infra rouge (CH2C12) : 3598 ; 2951 ; 1733 ; 1622 ; 1489 ; 1475 ; 1243 ; 1227 ;1031 ; 856 et 831 cm'1.Infra red spectrum (CH 2 Cl 2): 3598; 2951; 1733; 1622; 1489; 1475; 1243; 1227; 1031; 856 and 831 cm -1.

Le (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-(prop-2-ynyl)pipéridine-3-carboxylate de méthyle peut être préparé comme décrit dans 25 l’exemple 32.Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-carboxylate can be prepared as described in Example 32.

Exemple 59Example 59

Acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,3,5-trifluorophényl)prop-2-ynyl]pipéridine-3-carboxylique(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) propyl) -acrylic acid; 2-ynyl] piperidine-3-carboxylic acid

Une solution de 1,7 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl) 30 propyl]-l-[3-(2,3,5-trifluorophényl)prop-2-ynyl]pipéridine-3-carboxylate de méthyledans 17 cm3 de dioxanne additionnés de 2,58 cm3 de soude aqueuse 5N est aeitéependant 15 heures à une température voisine de 60°C. Après refroidissement à unetempérature voisine de 20°C, le mélange réactionnel est concentré sous pression 120 2 2 277 réduite (5 kPa) à une température voisine de 40°C. Le résidu obtenu est purifié parchromatographie sous une pression de 50 kPa d’azote, sur une colonne de gel de silice(granulométrie 20-45μ ; diamètre 3 cm ; 50 g), en éluant par un mélange dedichlorométhane-méthanol (90/10 en volumes) et en recueillant d’abord une fractionde 200 cm3, puis des fractions de 23 cm3. Les fractions 3 à 21 sont réunies, puisconcentrées comme précédemment. On obtient une meringue que l’on soumet à unedeuxième purification par chromatographie sous une pression de 50 kPa d’azote, surune colonne de gel de silice (granulométrie 20-45μ ; diamètre 3 cm ; 70 g), en éluantpar un mélange de dichlorométhane-méthanol (95/5 en volumes) et en recueillantd’abord une fraction de 250 cm3, puis une fraction de 100 cm3, puis des fractions de20 cm3. Les fractions 1 à 17 sont réunies, puis concentrées comme précédemment. Onobtient une meringue que reprend par du dichlorométhane, puis par 20 cm3 d’unmélange 50/50 de diisopropyloxyde et de pentane. Le produit cristallisé formé estfiltré, lavé par 2 fois 10 cm3 d’un mélange diisopropyloxyde-pentane (50/50 envolumes), puis 2 fois 10 cm3 de pentane, séché à l’air. On obtient 0,524 g d’acide(3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyI]-l-[3-(2,3,5-trifluoro-phényl)prop-2-ynyl]pipéridine-3-carboxylique, sous forme d’un solide de couleurcrème fondant vers 97°C.A solution of 1.7 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2H) Methyl 3,5-trifluorophenyl) prop-2-ynyl] piperidine-3-carboxylate in 17 cm 3 of dioxane supplemented with 2.58 cm 3 of 5N aqueous sodium hydroxide is stirred for 15 hours at a temperature in the region of 60 ° C. After cooling to a temperature in the region of 20 ° C., the reaction mixture is concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. The residue obtained is purified by chromatography under a pressure of 50 kPa of nitrogen, on a column of silica gel (particle size 20-45 μ, diameter 3 cm, 50 g), eluting with a dichloromethane-methanol mixture (90:10). volumes) and first collecting a fraction of 200 cm3, then fractions of 23 cm3. Fractions 3 to 21 are combined, puisconcentrées as previously. A meringue is obtained which is subjected to a second purification by chromatography under a pressure of 50 kPa of nitrogen, on a column of silica gel (particle size 20-45μ, diameter 3 cm, 70 g), eluting with a mixture of dichloromethane methanol (95/5 by volume) and first collecting a fraction of 250 cm3, then a fraction of 100 cm3, then fractions of 20 cm3. Fractions 1 to 17 are combined and then concentrated as before. A meringue is obtained which is taken up in dichloromethane and then in 20 cm3 of a 50/50 mixture of diisopropyloxide and pentane. The crystallized product formed is filtered off, washed with twice 10 cm 3 of a diisopropyloxide-pentane mixture (50/50 volumes), then 2 times 10 cm 3 of pentane, dried in air. 0.524 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl) -1- (3- (2,3-diisopropyl) -2- 5-trifluoro-phenyl) prop-2-ynyl] piperidine-3-carboxylic acid as a cream colored solid melting at about 97 ° C.

Spectre de R.M.N. (300 MHz, (CD3)2SO d6, δ en ppm) : on observe un mélangede diastéréoisomères dans les proportions 50/50. de 1,40 à 2,00 (mt : 7H) ; de 2,35 à 3,00 (mt : 5K) ; 3,65 et 3,66 (2s : 2H en totalité) ;3,90 et 3,92 (2s : 3H en totalité) ; 5,24 (mt : JH) ; 5,54 (mf : 1H) ; de 7,25 à 7,45 (mt:3Ï1) ; de 7,50 à 7,70 (mt : 2H) ; 7,94 (d, >9,5 Hz : 1H) ; 8,71(d, J = 4,5 Hz : IH). (3R,4R)-4-[3-(R,S)-bydroxy-3-(6-méihoxyqtrinolin-4-yI)propyl]-l-[3-(2,3,5-trifluorophényI)prop-2-ynyl] plpéridine-3-carboxylate de méthyleSpectrum of R.M.N. (300 MHz, (CD3) 2SO d6, δ in ppm): a mixture of diastereoisomers in the proportions 50/50 is observed. from 1.40 to 2.00 (mt: 7H); from 2.35 to 3.00 (mt: 5K); 3.65 and 3.66 (2s: 2H in all), 3.90 and 3.92 (2s: 3H in total); 5.24 (mt: JH); 5.54 (mf: 1H); from 7.25 to 7.45 (mt: 31); from 7.50 to 7.70 (mt: 2H); 7.94 (d,> 9.5 Hz: 1H); 8.71 (d, J = 4.5 Hz: 1H). (3R, 4R) -4- [3- (R, S) -bydroxy-3- (6-méihoxyqtrinolin-4-yl) propyl] -l- [3- (2,3,5-trifluorophényI) prop-2 -ynyl] methylpiperidine-3-carboxylate

Un mélange de 1,95 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-(prop-2-ynyl)pipéridine-3-carboxylate de méthyle dans 20 cm3 detriéthylamine est agité pendant 5 minutes sous atmosphère inerte à une températurevoisine de 20°C. On ajoute 0,284 g de tétrakis triphénylphosphine palladium, 0,094 gd’iodure cuivreux et 1,56 g de l-bromo-2,3,5-trifluorobenzène. Le mélange est agitépendant 2 heures 30 minutes à une température voisine de 80°C. Aprèsrefroidissement à environ 20°C, le mélange réactionnel est additionné de 60 cm3d’acétate d’éthyle et 60 cm3 d’eau. Après 30 minutes d’agitation, le mélange estdécanté. Après séparation de la phase organique, la couche aqueuse est extraite par3 fois 30 cm3 d’acétate d’éthyle. Les extraits organiques sont réunis, lavés par 3 fois 278 120 22 * 30 cm3 d’eau, séchés sur sulfate de sodium, filtrés, concentrés sous pression réduite(5 kPa) à une température voisine de 40°C. Le résidu obtenu est purifié parchromatographie sous une pression d’azote de 50 kPa, sur une colonne de gel de silice(granulométrie 20-45μ ; diamètre 4 cm ; 80 g), en éluant par de l’acétate d’éthyle puret en recueillant d’abord une fraction de 100 cm3, puis des fractions de 20 cm3. Lesfractions 23 à 27 sont réunies, concentrées comme ci-dessus. On obtient 1,3 g de(3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinoîin-4-yl)propyl]-l-[3-(2,3,5-trifluoro-phényl)prop-2-ynylJpipéridine-3-carboxylate de méthyle, sous forme d’une meringue.A mixture of 1.95 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) Piperidine-3-carboxylic acid methyl ester in 20 cm3 of triethylamine is stirred for 5 minutes under an inert atmosphere at a temperature of 20 ° C. 0.284 g of tetrakis triphenylphosphine palladium, 0.094 g of cuprous iodide and 1.56 g of 1-bromo-2,3,5-trifluorobenzene are added. The mixture is stirred for 2 hours 30 minutes at a temperature of 80 ° C. After cooling to about 20 ° C, the reaction mixture is supplemented with 60 cm3 of ethyl acetate and 60 cm3 of water. After stirring for 30 minutes, the mixture is decanted. After separation of the organic phase, the aqueous layer is extracted with 3 times 30 cm3 of ethyl acetate. The organic extracts are combined, washed with water 3 times, dried over sodium sulphate, filtered and concentrated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. The residue obtained is purified by chromatography under a nitrogen pressure of 50 kPa, on a column of silica gel (particle size 20-45 μ, diameter 4 cm, 80 g), eluting with pure ethyl acetate, collecting first a fraction of 100 cm3, then fractions of 20 cm3. Fractions 23 to 27 are joined, concentrated as above. 1.3 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinin-4-yl) propyl] -1- [3- (2,3 g) are obtained. Methyl 5-trifluoro-phenyl) prop-2-ynyl-piperidine-3-carboxylate, as a meringue.

Spectre infra rouge dans CC14: 2950 ; 1740 ; 1624 ; 1496 ; 1231 ; 1133 ; 861 et845 cm'1Infra red spectrum in CC14: 2950; 1740; 1624; 1496; 1231; 1133; 861 and845 cm'1

Le (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(prop-2-ynyl)pipéridine-3-carboxylate de méthyle peut être préparé comme décrit dansl’exemple 32.Methyl (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- (prop-2-ynyl) piperidine-3-carboxylate can be prepared as described in Example 32.

Exemple 60 Acide (3R,4R)-4-[3-(R,S)-fïuoro-3-(6-méthoxyquinolin-4- yl)propyi]-l-l2-(2-thiénylthio)éthyl]pipéridine-3-acétiqueExample 60 (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1-2- (2-thienylthio) ethyl] piperidine-3 acid -acetic

Un mélange de 1,28 g de (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2-thiénylthio)éthyl]pipéridine-3-acétate de méthyle dans 25 cm3 dedioxanne, additionné de 2 cm3 de soude aqueuse 5N, est agité pendant 18 heures à unetempérature voisine de 60°C. Après évaporation sous pression réduite (5 kPa) à unetempérature voisine de 50°C, le résidu est repris par 50 cm3 d’acétone. L’acétone estévaporée sous pression réduite (5 kPa) à une température voisine de 50°C. Le résiduest repris par 75 cm3 d’eau et 100 cm3 de dichlorométhane. La phase organique estséparée. La phase aqueuse est extraite 2 fois par 100 cm3 de dichlorométhane, puis lesextraits organiques sont réunis, séchés sur sulfate de sodium, filtrés, évaporés souspression réduite (5 kPa) à une température voisine de 40°C. Le solide obtenu estrepris par 50 cm3 d’éther de diéthyîe et la suspension obtenue est agitée durant48 heures à une température voisine de 20°C. Le solide est filtre, rincé par 75 cm3 autotal d’éther de diéthyîe puis séché sous pression réduite (5 kPa) à une températurevoisine de 40°C. On obtient 1 g de solide que l’on purifie par chromatographie sousune pression de 100 kPa d’azote sur une colonne de gel de silice (granulométrie 60-200μ ; diamètre 2 cm ; hauteur silice 15 cm), en éluant par un mélange chloroforme-méthanol-ammoniaque (24/6/1 en volumes), et en recueillant des fractions de 20 cm3.Les fractions contenant le produit sont réunies et évaporées sous pression réduite(5 kPa) à une température voisine de 40°C. On obtient 0,97 g d’acide (3R,4R)-4-[3- 120 2 2 279 (R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2-thiénylthio)éthyl] pipéridine-3-acétique, sous forme d’une meringue blanche qui est un mélange de deuxdiastéréo isomères.A mixture of (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio), 1.28 g. ) ethyl] piperidine-3-methyl acetate in 25 cm3 of dioxane, supplemented with 2 cm3 of 5N aqueous sodium hydroxide, is stirred for 18 hours at a temperature of 60 ° C. After evaporation under reduced pressure (5 kPa) at a temperature of 50 ° C, the residue is taken up in 50 cm3 of acetone. Acetone is evaporated under reduced pressure (5 kPa) at a temperature of 50 ° C. The residue is taken up in 75 cm3 of water and 100 cm3 of dichloromethane. The organic phase is separated. The aqueous phase is extracted twice with dichloromethane (100 cc) and the organic extracts are combined, dried over sodium sulphate, filtered and evaporated under reduced pressure (5 kPa) at a temperature in the region of 40.degree. The solid obtained is taken with 50 cm3 of diethyl ether and the suspension obtained is stirred for 48 hours at a temperature in the region of 20 ° C. The solid is filtered, rinsed with 75 cm3 autotal diethyl ether and dried under reduced pressure (5 kPa) at a temperature of 40 ° C. 1 g of solid is obtained which is purified by chromatography under a pressure of 100 kPa of nitrogen on a column of silica gel (particle size 60-200 μ, diameter 2 cm, silica height 15 cm), eluting with a chloroform mixture. -methanol-ammonia (24/6/1 by volume), and collecting fractions of 20 cm3. The fractions containing the product are combined and evaporated under reduced pressure (5 kPa) at a temperature of 40 ° C. 0.97 g of (3R, 4R) -4- [3- (2,2,679 g) (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2 is obtained. - (2-thienylthio) ethyl] piperidine-3-acetic acid, in the form of a white meringue which is a mixture of two diastereoisomers.

Spectre de R.M.N. (400 MHz, (CD3)2SO d6 avec ajout de quelques gouttes deCD3COOD d4, δ en ppm). On observe un mélange de deux diastéréoisomères dans lesproportions 50/50 : de 1,15 à 1,65 (mt : 5H) ; 1,90 à 2,60 (mt : 7H) ; 2,61 (mt : 2H) ; 2,78 (mt : 2H) ; 2,93 (t large, J = 7 Hz : 2H) ; 3,92 et 3,93 (2 s : 3H en totalité) ; 6,36(mt, J HF = 48 Hz : 1H) ; 7,04 (dd, J = 5,5 et 3,5 Hz : 1H) ; 7,18 (dd, J = 3,5 et 1 Hz :1H) ; 7,29 (mt : 1H) ; 7,44 (mt : 1H) ; 7,49 (d large, J = 4,5 Hz : 1H) ; 7,59 (dd, J = 5,5 et 1 Hz : 1H) ; 7,98 (d large, J = 9 Hz : 1H) ; 8,77 (d, J = 4,5 Hz : 1H). (3R,4R)-4-[3-(R,S)-FIuoro-3-(6-méthoxyquinolin-4-yl)propyI]-l-[2-(2- thiénylthio)éthyI]pipéridine-3-acétate de méthyle A une solution agitée de 1,96 g de (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2-thiénylthio)éthyl]pipéridine-3-acétate de méthyle dans 15 cm3 de dichlorométhane, on ajoute sous atmosphère inerte et à unetempérature voisine de 20°C, 0,62 cm3 de diéthylaminosulfure trifluorure enapproximativement 15 minutes L’agitation est maintenue durant 18 heures. Aprèsaddition de 30 cm3 d’une solution aqueuse saturée d’hydrogénocarbonate de sodium,la phase organique est décantée. La phase aqueuse est extraite 2 fois p< r 50 cm3 dedichlorométhane, puis les extraits organiques sont réunis, lavés 2 fois par 50 cm3d’eau distillée, séchés sur sulfate de sodiuru, filtrés, évaporés sous pression réduite(5 kLa) à une température voisine de 4Q°C. On obtient 1,95 g d’une huile jaune quel’on purifie par chromatographie sous une pression de 100 kPa d’azote sur unecolonne de gel de silice (granulométrie 20-45μ ; diamètre 3 cm ; hauteur silice40 cm), en éluant par un mélange cyclohexane-acétate d’éthyle (3/2 en volumes), eten recueillant des fractions de 80 cm3. On réunit les fractions 32 à 64 que l’on évaporesous pression réduite (5 kPa) à une température voisine de 40°C. On obtient 1,28 g de(3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxy-quinolin-4-yl)propyl]-l-[2-(2- thiénylthio)éthyl]pipéridine-3-acétate de méthyle sous forme d’une huile incolore.Spectrum of R.M.N. (400 MHz, (CD3) 2SO d6 with addition of a few drops ofCD3COOD d4, δ in ppm). There is a mixture of two diastereoisomers in the proportions 50/50: from 1.15 to 1.65 (mt: 5H); 1.90 to 2.60 (mt: 7H); 2.61 (mt: 2H); 2.78 (mt: 2H); 2.93 (broad t, J = 7 Hz: 2H); 3.92 and 3.93 (2 s: 3H in total); 6.36 (mt, J HF = 48 Hz: 1H); 7.04 (dd, J = 5.5 and 3.5 Hz: 1H); 7.18 (dd, J = 3.5 and 1 Hz: 1H); 7.29 (mt: 1H); 7.44 (mt: 1H); 7.49 (broad d, J = 4.5 Hz: 1H); 7.59 (dd, J = 5.5 and 1 Hz: 1H); 7.98 (broad d, J = 9 Hz: 1H); 8.77 (d, J = 4.5 Hz: 1H). (3R, 4R) -4- [3- (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-acetate To a stirred solution of 1.96 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- Methyl (2-thienylthio) ethyl] piperidine-3-acetate in 15 cm3 of dichloromethane is added under an inert atmosphere and at a temperature of 20 ° C, 0.62 cm3 of diethylaminosulfide trifluoride approximately 15 minutes The stirring is maintained during 18 hours. Afteraddition of 30 cm3 of a saturated aqueous solution of sodium hydrogencarbonate, the organic phase is decanted. The aqueous phase is extracted twice with 50 cm 3 of dichloromethane and the organic extracts are combined, washed twice with 50 cm 3 of distilled water, dried over sodium sulfate, filtered and evaporated under reduced pressure (5 kla) at a temperature of 50.degree. close to 40 ° C. 1.95 g of a yellow oil which is purified by chromatography under a pressure of 100 kPa of nitrogen on a column of silica gel (particle size 20-45 μ, diameter 3 cm, silica height 40 cm), eluting with a cyclohexane-ethyl acetate mixture (3/2 by volume), and collecting fractions of 80 cm3. Fractions 32 to 64 are combined and evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 1.28 g of (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxy-quinolin-4-yl) propyl] -1- [2- (2- (4R) -3- thienylthio) ethyl] piperidine-3-methyl acetate as a colorless oil.

Spectre de R.M.N. (300 MHz, (CD3)2SO d6, δ en ppm). On observe un mélange dedeux diastéréoisomères dans les proportions 60/40 : de 1,10 à 1,60 (mt : 5H) ; 1,85 à 2,15 (mt : 6H) ; de 2,20 à 2,80 (mt : 5H) ; 2,88 (t large, J = 7 Hz : 2H) ; 3,53 et 3,55 (2s : 3H en totalité) ; 3,93 et 3,94 (2 s : 3H en totalité) ; 6,40 (mt, J HF = 48 Hz : 1H) ; 280 120 2 2 7,03 (dd, J = 5,5 et 3,5 Hz : 1H) ; 7,15 (d large, J = 3,5 Hz : 1H) ; 7,30 (d large, J = 1,5 Hz : 1H) ; 7,46 (dd, J = 9 et 1,5 Hz : 1H) ; 7,49 (d large, J = 4,5 Hz : 1H) ; 7,60(dd, J = 5,5 et 1 Hz : 1H) ; 7,99 (d large, J = 9 Hz : 1H) ; 8,79 (d, J = 4,5 Hz : 1H).Spectrum of R.M.N. (300 MHz, (CD3) 2SO d6, δ in ppm). There is a mixture of two diastereoisomers in the proportions 60/40: from 1.10 to 1.60 (mt: 5H); 1.85 to 2.15 (mt: 6H); from 2.20 to 2.80 (mt: 5H); 2.88 (broad t, J = 7 Hz: 2H); 3.53 and 3.55 (2s: 3H in total); 3.93 and 3.94 (2 s: 3H in total); 6.40 (mt, J HF = 48 Hz: 1H); 280 120 2 273.03 (dd, J = 5.5 and 3.5 Hz: 1H); 7.15 (broad, J = 3.5 Hz: 1H); 7.30 (broad d, J = 1.5 Hz: 1H); 7.46 (dd, J = 9 and 1.5 Hz: 1H); 7.49 (broad d, J = 4.5 Hz: 1H); 7.60 (dd, J = 5.5 and 1 Hz: 1H); 7.99 (d, J = 9 Hz: 1H); 8.79 (d, J = 4.5 Hz: 1H).

Le (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2-thiényI-thio)éthyl]pipéridine-3-acétate de méthyle est préparé comme décrit à l’exemple 48.(3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine- 3-methyl acetate is prepared as described in Example 48.

Exemple 61Example 61

Acide (3R,4R)-4-[3-fluoro-3-(6-méthoxyquinoIin-4-yl)propyI]-l-[2-(2-(3R, 4R) -4- [3-fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-

thiénylthio)éthyl] pipéridine-3-acétique, diastéréoisomère A 0,5 g de (3R,4R)-4-[3-fluoro-3-(6-méthoxyquinolin-4-yl) propyl]-1-(2-(2-thiénylthio)éthyl] pipéridine-3-acétate de méthyle, diastéréoisomère A (aD20= -48 ±3dans le méthanol) dans 10 cm3 de dioxanne, additionné de 0.77 cm3 de soude aqueuse5N, est agité pendant 18 heures à une température voisine de 60°C. Après évaporationsous pression réduite (5 kPa) à une température voisine de 50°C, on obtient 0,6 g desolide que l’on purifie par chromatographie sous une pression de 100 kPa d’azote surune colonne de gel de silice (granulométrie 20-45μ ; diamètre 2 cm ; hauteur silice 30cm), en éluant par un mélange chloroforme-méthanol-ammoniaque (24/6/1 envolumes), et en recueillant des fractions de 20 cm3. Les fractions contenant le produitsont réunies et évaporées sous pression réduite (5 kPa) à une température voisine de40°C. On obtient 0,27 g d’acide (3R,4R)-4-[3-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2-thiénylthio)éthyl] pipéridine-3-acétique, diastéréoisomère A, sousforme d’une meringue blanche. (aD20= -66_±1.2 dans le méthanol).thienylthio) ethyl] piperidine-3-acetic acid, diastereoisomeric A 0.5 g of (3R, 4R) -4- [3-fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (2- ( 2-thienylthio) ethyl] piperidine-3-methyl acetate, diastereoisomer A (aD20 = -48 ± 3 in methanol) in 10 cm3 of dioxane, added with 0.77 cm3 of 5N aqueous sodium hydroxide, is stirred for 18 hours at a temperature in the region of 60 ° C. After evaporation under reduced pressure (5 kPa) at a temperature in the region of 50 ° C., 0.6 g of desolide are obtained, which is purified by chromatography under a pressure of 100 kPa of nitrogen on a column of silica gel. (granulometry 20-45μ, diameter 2 cm, silica height 30cm), eluting with a chloroform-methanol-ammonia mixture (24/6/1 volumes), and collecting fractions of 20 cm3 .The fractions containing the product are combined and evaporated under reduced pressure (5 kPa) at a temperature in the region of 40 ° C. 0.27 g of (3R, 4R) -4- [3-fluoro-3- (6-methoxyquinoli) acid are obtained n-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-acetic acid, diastereoisomer A, in the form of a white meringue. (aD20 = -66_ ± 1.2 in methanol).

Spectre de R.M.N. (300 MHz, (CD3)2SO d6, δ en ppm) : de 1,20 à 1,55 (mt : 5H) ;de 1,85 à 2,20 et de 2,35 à 2,60 (2 séries de mts : 9H en totalité) ; 2,68 (mt : 2H) ; 2,89 (t large, J = 7 Hz : 2H) ; 3,94 (s : 3H) ; 6,38 (mt, JHF = 48 Hz : 1H) ; 7,05 (dd, J = 5,5 et 3,5 Hz : 1H) ; 7,17 (dd, J = 3,5 et 1 Hz : 1H) ; 7,32 (d, J = 2,5 Hz : 1H) ; 7,45(dd, J = 9 et 2,5 Hz : 1H) ; 7,51 (d, J = 4,5 Hz : 1H) ; 7,60 (dd, J = 5,5 et 1 Hz : 1H) ; 7,99 (d, J = 9 Hz : 1H) ; 8,78 (d, J = 4,5 Hz : 1H).Spectrum of R.M.N. (300 MHz, (CD3) 2SO d6, δ in ppm): from 1.20 to 1.55 (mt: 5H), from 1.85 to 2.20 and from 2.35 to 2.60 (2 sets of mts: 9H in total); 2.68 (mt: 2H); 2.89 (broad t, J = 7 Hz: 2H); 3.94 (s: 3H); 6.38 (mt, JHF = 48 Hz: 1H); 7.05 (dd, J = 5.5 and 3.5 Hz: 1H); 7.17 (dd, J = 3.5 and 1 Hz: 1H); 7.32 (d, J = 2.5 Hz: 1H); 7.45 (dd, J = 9 and 2.5 Hz: 1H); 7.51 (d, J = 4.5 Hz: 1H); 7.60 (dd, J = 5.5 and 1 Hz: 1H); 7.99 (d, J = 9 Hz: 1H); 8.78 (d, J = 4.5 Hz: 1H).

(3R,4R)-4-[3-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2-thiénylthio)éthyl]pipéridine-3-acétate de méthyle, diastéréoisomère A t (3R,4R)-4-[3-fluoro-3-(6-méthoxyquinolin-4-yl)propvlJ-l-[2-(2-thiénylthio)éthyl]pipéridine-3-acétate de méthyle, diastéréoisomère B x 120 2 2 281 3,2 g du (3R,4R)-4-[3-(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1-(2-(2-thiénylthio) éthyl]pipéridine-3-acétate de méthyle est chromatographie sur unecolonne de 30 cm de long et 8 cm de diamètre, conditionnée avec 1200 g de siliceChiralcel OD (granulométrie 20μ). L’élution est effectuée à l’aide d’un mélange deheptane-isopropanol (90/10 en volumes) Le débit est de 140 cm3/minute. La détectionest effectuée en ultra violet à 265nm. Après plusieurs injections préparatives, onrecueille les fractions correspondant aux diastéréoisomères A et B. Les fractionscontenant la diastéréoisomères A sont concentrées sous pression réduite (5 kPa) à unetempérature voisine de 40°C. On obtient 1,6 g de (3R,4R)-4-[3-fluoro-3-(6-méthoxyquinolin-4-yl)propy 1]-1 - [2-(2-thiénylthio)éthyl]pipéridine-3-acétate de méthyle, diastéréoisomère A sous foime d’une huile épaisse. (aD20 = -48 +/-3 dans leméthanol à 0,1%). Les fractions contenant la diastéréoisomères B sont concentréesdans les mêmes conditions que ci-dessus. On obtient 1,17 g (3R,4R)-4-[3-fluoro-3-(6-méthoxyquinolin-4-y l)propyl]-1 -[2-(2-thiénylthio)éthyl]pipéridine-3-acétate de méthyle, diastéréoisomère B, sous forme d’une huile épaisse. (<xD20 =+82 +/-3 dans leméthanol à 0,1%). diastéréoisomère A :Methyl (3R, 4R) -4- [3-fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-acetate, diastereoisomer At t Methyl (3R, 4R) -4- [3-fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-acetate, diastereoisomer B x 120 3.2 g of (3R, 4R) -4- [3- (R, S) -fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- (2- (2-thienylthio) Methyl] piperidine-3-methyl acetate is chromatographed on a column 30 cm long and 8 cm in diameter, packed with 1200 g of silica Chiralcel OD (particle size 20 μ) elution is carried out using a mixture deheptane-isopropanol (90/10 by volume) The flow rate is 140 cm3 / minute.The detection is carried out in ultraviolet at 265 nm.After several preparative injections, the fractions corresponding to the diastereoisomers A and B are collected.The fractions containing the diastereoisomers A are concentrated. under reduced pressure (5 kPa) at a nearby temperature At 40 ° C., 1.6 g of (3R, 4R) -4- [3-fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1 - [2- (2-thienylthio) are obtained. ) ethyl] piperidine-3-methyl acetate, diastereoisomer A under foime of a thick oil. (aD20 = -48 +/- 3 in 0.1% ethanol). The fractions containing the diastereoisomers B are concentrated under the same conditions as above. 1.17 g (3R, 4R) -4- [3-fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-acetate are obtained. of methyl, diastereoisomer B, in the form of a thick oil. (<xD20 = + 82 +/- 3 in 0.1% ethanol). diastereoisomer A:

Spectre infra rouge (KBr) 2936 ; 2861 ; 2805 ; 2768 ; 1731 ; 1623 ; 1594 ; 1508 ; 1475 ; 1435 ; 1359 ; 1229 ; 1217 ; 1167 ; 1108 ; 1084 ; 1030 ; 855 ; 847 et 830 cm’1. diastéréoisomère B :Infrared spectrum (KBr) 2936; 2861; 2805; 2768; 1731; 1623; 1594; 1508; 1475; 1435; 1359; 1229; 1217; 1167; 1108; 1084; 1030; 855; 847 and 830 cm -1. diastereoisomer B:

Spectre infra rouge (KBr) 2932 ; 2861 ; 2805 ; 2768 ; 1731 ; 1623 ; 1594 ; 1509 ; 1475 ; 1435 ; 1359 ; 1229 ; 1217 ; 1168 ; 1108 ; 1083 ; 1030 ; 855 ; 847 et 830 cm'1.Infrared spectrum (KBr) 2932; 2861; 2805; 2768; 1731; 1623; 1594; 1509; 1475; 1435; 1359; 1229; 1217; 1168; 1108; 1083; 1030; 855; 847 and 830 cm -1.

Le (3R,4R)-4-[3(R,S)-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2-thiénylthio)éthyl] pipéridine-3-acétate de méthyle est préparé comme décrit précédemment àl'exemple 60.(3R, 4R) -4- [3 (R, S) -Fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-acetate Methyl is prepared as described previously in Example 60.

Exemple 62Example 62

Acide (3R,4R)-4-[3-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2-(3R, 4R) -4- [3-fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2-

thiénylthio)éthyl] pipéridine-3-acétique, diastéréoisomère Bthienylthio) ethyl] piperidine-3-acetic acid, diastereoisomer B

En opérant comme décrit à l'exemple 60, mais à partir de 0,5 de (3R,4R)-4-[3-fluoro-3-(6-méthoxyquindin-4-yl) propyl)-1 -[2-(2-thiénylthio)éthyl]pipéridine-3-acétate deméthyle, diastéréoisomère B (ocD20= +82) on obtient 0,29 g d’acide (3R,4R)-4-[3-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2-thiénylthio)éthyl]pipéridine-3-acétique, diastéréoisomère B, sous forme d’une meringue blanche (aD20= +66.3±1.1) 120 22 282Working as described in Example 60, but starting from 0.5 of (3R, 4R) -4- [3-fluoro-3- (6-methoxyquindin-4-yl) propyl) -1- [2- (2-thienylthio) ethyl] piperidine-3-methyl acetate, diastereoisomer B (ocD20 = +82) gives 0.29 g of (3R, 4R) -4- [3-fluoro-3- (6-methoxyquinolinic acid) 4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-acetic acid, diastereoisomer B, as a white meringue (aD20 = + 66.3 ± 1.1) 120 22 282

Spectre de R.M.N. ^H (300 MHz, (CD3)2SO d6, δ en ppm) : de 1,20 à 1,60 (mt : 5H) ;de 1,90 à 2,15 et de 2,30 à 2,60 (2 séries de mts : 9H en totalité) ; 2,68 (mt : 2H) ; 2,89 (t large, J = 7 Hz : 2H) ; 3,95 (s : 3H) ; 6,38 (mt, JHF = 48 Hz : 1H) ; 7,05 (dd, J = 5,5 et 3,5 Hz : 1H) ; 7,18 (dd, J = 3,5 et 1 Hz : 1H) ; 7,32 (d, J = 2,5 Hz : 1H) ; 7,46(dd, J = 9 et 2,5 Hz : 1H) ; 7,51 (d, J = 4,5 Hz : 1H) ; 7,61 (dd, J = 5,5 et 1 Hz : 1H) ; 7,99 (d, J = 9 Hz : 1H) ; 8,78 (d, J = 4,5 Hz : 1H).Spectrum of R.M.N. ^ H (300 MHz, (CD3) 2SO d6, δ in ppm): from 1.20 to 1.60 (mt: 5H), from 1.90 to 2.15 and from 2.30 to 2.60 (2 series of mts: 9H in total); 2.68 (mt: 2H); 2.89 (broad t, J = 7 Hz: 2H); 3.95 (s: 3H); 6.38 (mt, JHF = 48 Hz: 1H); 7.05 (dd, J = 5.5 and 3.5 Hz: 1H); 7.18 (dd, J = 3.5 and 1 Hz: 1H); 7.32 (d, J = 2.5 Hz: 1H); 7.46 (dd, J = 9 and 2.5 Hz: 1H); 7.51 (d, J = 4.5 Hz: 1H); 7.61 (dd, J = 5.5 and 1 Hz: 1H); 7.99 (d, J = 9 Hz: 1H); 8.78 (d, J = 4.5 Hz: 1H).

Le (3R,4R)-4-[3-fluoro-3-(6-méthoxyquinolin-4-yl)propyl]-1 -[2-(2-thiénylthio) éthyl]pipéridine-3-acétate de méthyle, diastéréoisomère B, est préparé comme décritprécédemment à l'exemple 61.Methyl (3R, 4R) -4- [3-fluoro-3- (6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-acetate, diastereoisomer B , is prepared as described previously in Example 61.

Exemple 63Example 63

Acide (3R,4R)-4-[3-hydroxy-3-(6-méthoxyquinoIin-4-yI)propyI]-l-[3-(2,3,5- trifïuoro-phényl)prop-2-ynyI]pipéridine-3-carboxyIique, diastéréoisomère A et(3R, 4R) -4- [3-Hydroxy-3- (6-methoxyquinin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-yl] acid piperidine-3-carboxylic acid, diastereoisomer A and

Acide (3R,4R)-4-[3-hydroxy-3-(6-méthoxyquinolin-4-yI)propyIJ-l-[3-(2,3,5-(3R, 4R) -4- [3-Hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5) -acrylic acid;

trifluoro-phényl)prop-2-ynyl]pipéridme-3-carboxylique, diastéréoisomère B 1,50 g d’acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,3,5-trifluorophényl)prop-2-ynyl]pipéridine-3-carboxylique dissous dans 200 cm3de dichloro-méthane est chromatographié sur une colonne de 30 cm et de 6 cm dediamètre conditionnée avec 700 g de silice Kromasil® (granulométrie 10 μ).L’élution est effectuée à l’aide d’un mélange dichlorométhane acétonitrile- -méthanoldans des proportions 90/5/5 en volumes. Le débit est de 130 cm3 par minute et ladétection effectuée en ultra violet à 265 nm. Cette opération conduit après quatreinjections préparatives à l’obtention des deux diastéréoisomères. Les fractionscorrespondant au premier sont concentrées à sec sous pression réduite (5 kPa) à unetempérature voisine de 40°C, puis le résidu obtenu est séché à l’étuve sous pressionréduite (13 Pa) à une température voisine de 40°C.. On obtient 1,9 g d’acide (3R,4R)- 4-[3-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,3,5-trifluorophényl) prop-2-ynyl]pipéridine-3-carboxylique, diastéréoisomère A. (ccD20= -50.9°+/-l,4, dans leméthanol à 0,5 %), sous forme d’une meringue.trifluoro-phenyl) prop-2-ynyl] piperidin-3-carboxylic acid, diastereoisomer B 1.50 g of (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolinic acid) 4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] piperidine-3-carboxylic acid dissolved in 200 cm3 of dichloromethane is chromatographed on a 30 cm column and 6 cm diameter measured with 700 g of Kromasil® silica (particle size 10 μ) .The elution is carried out using a mixture of dichloromethane acetonitrile-methanol in proportions of 90/5/5 by volume. The flow rate is 130 cm3 per minute and the detection carried out in ultraviolet at 265 nm. This operation leads after four injections preparatory to obtaining the two diastereoisomers. The fractions corresponding to the first are concentrated to dryness under reduced pressure (5 kPa) at a temperature close to 40 ° C., and the residue obtained is then dried in an oven under reduced pressure (13 Pa) at a temperature in the region of 40 ° C. 1.9 g of (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop) is obtained. -2-ynyl] piperidine-3-carboxylic acid, diastereoisomer A (ccD20 = -50.9 ° +/- 1.4 in 0.5% ethanol), as a meringue.

Spectre de R.M.N. ^H (300 MHz, (CD3)2SO d6, δ en ppm) : de 1,40 à 2,00 (mt : 7H) ; de 2,35 à 3,00 (mt : 5H) ; 3,66 (s : 2H) ; 3,92 (s : 3H entotalité) ; 5,24 (mt : 1H) ; 5,54 (mf : 1H) ; de 7,25 à 7,45 (mt: 3H) ; de 7,50 à 7,70(mt : 2H) ; 7,94 (d, J=9,5 Hz : 1 H) ; 8,7l(d, J = 4,5 Hz : 1 H). 12 0 2 2 283Spectrum of R.M.N. H (300 MHz, (CD3) 2SO d6, δ in ppm): from 1.40 to 2.00 (mt: 7H); from 2.35 to 3.00 (mt: 5H); 3.66 (s: 2H); 3.92 (s: 3H entotality); 5.24 (mt: 1H); 5.54 (mf: 1H); from 7.25 to 7.45 (mt: 3H); from 7.50 to 7.70 (mt: 2H); 7.94 (d, J = 9.5 Hz: 1H); 8.71 (d, J = 4.5 Hz: 1H). 12 0 2 2 283

Les fractions correspondant au second diastéréoisomère sont traitées commeprécédemment On obtient 2,17 g d’acide (3R,4R)-4-[3-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,3,5-trifluorophényl)prop-2-ynyl]pipéridine-3-carboxylique, diastéréoisomère B. (aD20=+67.8°+/-l,2, dans le méthanol à 0,5 %),sous forme d’une meringue.Fractions corresponding to the second diastereoisomer are treated as before. 2.17 g of (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] piperidine-3-carboxylic acid, diastereoisomer B. (aD20 = + 67.8 ° +/- 1.2, in 0.5% methanol), in the form of a meringue.

Spectre de R.M.N. (300 MHz, (CD3)2SO d6, δ en ppm) : de 1,40 à 2,00 (mt : 7H) ; de 2,35 à 3,00 (mt : 5H) ; 3,65 (s : 2H) ; 3,90 (s : 3H entotalité) ; 5,24 (mt : 1H) ; 5,54 (mf : 1H) ; de 7,25 à 7,45 (mt: 3H) ; de 7,50 à 7,70(mt : 2H) ; 7,94 (d, J=9,5 Hz : 1H) ; 8,71(d; J = 4,5 Hz : 1H). L’acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,3,5-trifluoro-phényl)prop-2-ynyl3pipéridme-3-carboxylique peut être préparé commedécrit à l’exemple 59.Spectrum of R.M.N. (300 MHz, (CD3) 2SO d6, δ in ppm): from 1.40 to 2.00 (mt: 7H); from 2.35 to 3.00 (mt: 5H); 3.65 (s: 2H); 3.90 (s: 3H entotality); 5.24 (mt: 1H); 5.54 (mf: 1H); from 7.25 to 7.45 (mt: 3H); from 7.50 to 7.70 (mt: 2H); 7.94 (d, J = 9.5 Hz: 1H); 8.71 (d, J = 4.5 Hz: 1H). (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro- phenyl) prop-2-ynylpiperidin-3-carboxylic acid can be prepared as described in Example 59.

La présente invention concerne également les compositions pharmaceutiquescontenant au moins un dérivé de quinolyl propyl pipéridine selon l'invention, le caséchéant sous forme de sel, à l'état pur ou sous forme d'une association avec un ouplusieurs diluants ou adjuvants compatibles et pharmaceutiquement acceptables.The present invention also relates to pharmaceutical compositionscontaining at least one quinolylpropylpiperidine derivative according to the invention, the caséchéant in salt form, in the pure form or in the form of an association with one or more diluents or adjuvants compatible and pharmaceutically acceptable .

Les compositions selon l’invention peuvent être utilisées par voie orale, parentérale,topique, rectale ou en aérosols.The compositions according to the invention can be used orally, parenterally, topically, rectally or in aerosols.

Comme compositions solides pour adminisiration orale peuvent être utilisés descomprimés, des pilules, des gélules, des poudres ou des granulés. Dans cescompositions, le produit actif selon l'invention est mélangé à un ou plusieurs diluantsou adjuvants inertes, tels que saccharose, lactose ou amidon. Ces compositionspeuvent comprendre des substances autres que les diluants, par exemple un lubrifianttel que le stéarate de magnésium ou un enrobage destiné à une libération contrôlée.As solid compositions for oral administration may be used tablets, pills, capsules, powders or granules. In these compositions, the active product according to the invention is mixed with one or more inert diluents or adjuvants, such as sucrose, lactose or starch. These compositions may include substances other than diluents, for example a lubricant such as magnesium stearate or a coating for controlled release.

Comme compositions liquides pour administration orale, on peut utiliser des solutionspharmaceutiquement acceptables, des suspensions, des émulsions, des sirops et desélixirs contenant des diluants inertes tels que l'eau ou l'huile de paraffine. Cescompositions peuvent également comprendre des substances autres que les diluants,par exemple des produits mouillants, édulcorants ou aromatisants.As liquid compositions for oral administration, it is possible to use pharmaceutically acceptable solutions, suspensions, emulsions, syrups and elixirs containing inert diluents such as water or paraffin oil. These compositions may also include substances other than diluents, for example wetting, sweetening or flavoring products.

Les compositions pour administration parentérale, peuvent être des solutions stérilesou des émulsions. Comme solvant ou véhicule, on peut employer l’eau, lepropylèneglycol, un polyéthylèneglycol, des huiles végétales, en particulier l'huile 120 22 284 d’olive, des esters organiques injectables, par exemple l'oléate d'éthyle. Cescompositions peuvent également contenir des adjuvants, en particulier des agentsmouillants, isotonisants, émulsifiants, dispersants et stabilisants.The compositions for parenteral administration may be sterile solutions or emulsions. As the solvent or vehicle, water, propylene glycol, polyethylene glycol, vegetable oils, in particular olive oil, injectable organic esters, for example ethyl oleate, may be used. These compositions may also contain adjuvants, in particular wetting agents, isotonic agents, emulsifiers, dispersants and stabilizers.

La stérilisation peut se faire de plusieurs façons, par exemple à l'aide d'un filtre5 bactériologique, par irradiation ou par chauffage. Elles peuvent également êtrepréparées sous forme de compositions solides stériles qui peuvent être dissoutes au moment de l'emploi dans de l'eau stérile ou tout autre milieu stérile injectable.Sterilization can be done in several ways, for example using a bacteriological filter, by irradiation or by heating. They can also be prepared as sterile solid compositions that can be dissolved at the time of use in sterile water or any other sterile injectable medium.

Les compositions pour administration topique peuvent être par exemple des crèmes,des pommades, des lotions ou des aérosols. 10 Les compositions par administration rectale sont les suppositoires ou les capsulesrectales, qui contiennent outre le principe actif, des excipients tels que le beurre decacao, des glycérides semi-synthétiques ou des polyéthylèneglycols.The compositions for topical administration may be, for example, creams, ointments, lotions or aerosols. The compositions by rectal administration are suppositories or rectal capsules, which contain, in addition to the active ingredient, excipients such as decaffeinated butter, semi-synthetic glycerides or polyethylene glycols.

Les compositions peuvent également être des aérosols. Pour l'usage sous formed'aérosols liquides, les compositions peuvent être des solutions stériles stables ou des 15 compositions solides dissoutes au moment de l'emploi dans de l'eau stérile apyrogène,dans du sérum ou tout autre véhicule pharmaceutiquement acceptable. Pour l'usagesous forme d'aérosols secs destinés à être directement inhalés, le principe actif estfinement divisé et associé à un diluant ou véhicule solide hydrosoluble d'unegranulométrie de 30 à 80 pm, par exemple le dextrane, le mannitol ou le lactose. 20 En thérapeutique humaine, les nouveaux dérivés de quinolyl propyl pipéridine selonl'invention sont particulièrement utiles dans le traitement des infections d'originebactérienne. Les doses dépendent de l'effet recherché et de la durée du traitement. Lemédecin déterminera la posologie qu'il estime la plus appropriée en fonction du traite-ment, en fonction de l'âge, du poids, du degré de l'infection et des autres facteurs 25 propres au sujet à traiter. Généralement, les doses sont comprises entre 750 mg et 3 gde produit actif en 2 ou 3 prises par jour par voie orale ou entre 400 mg et 1,2 g parvoie intraveineuse pour un adulte. L'exemple suivant illustre une composition selon l'invention. EXEMPLE 1 30 On prépare selon la technique habituelle une composition liquide destinée à l’usage t parentéral comprenant : 120 2 2 285 • acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-1 -(2-(2- thiénylthio)éthyl] pipéridine-3-carboxylique ........................ 125 mg • glucose qsp 2,5% • hydroxyde de sodium qsp pH = 4-4,5 5 · eauppi ......................... qsp 20 ml EXEMPLE 2The compositions may also be aerosols. For use as liquid aerosols, the compositions may be stable sterile solutions or solid compositions dissolved at the time of use in sterile, pyrogen-free water, in serum or other pharmaceutically acceptable carrier. For use in the form of dry aerosols intended to be directly inhaled, the active ingredient is finely divided and associated with a diluent or solid water-soluble carrier of a granulometry of 30 to 80 pm, for example dextran, mannitol or lactose. In human therapy, the novel quinolylpropylpiperidine derivatives according to the invention are particularly useful in the treatment of bacterial infections. The doses depend on the desired effect and the duration of the treatment. Lemédecin will determine the dosage he considers the most appropriate treatment depending on the age, weight, degree of infection and other factors specific to the subject to be treated. Generally, the doses are between 750 mg and 3 g of active product in 2 or 3 doses per day or between 400 mg and 1.2 g intravenous for an adult. The following example illustrates a composition according to the invention. EXAMPLE 1 A liquid composition for parenteral use comprising: (3R, 4R) -4- [3- (R, S) -hydroxy-3 (6) acid) is prepared by the usual method; -methoxyquinolin-4-yl) propyl] -1- (2- (2-thienylthio) ethyl] piperidine-3-carboxylic acid ....................... 125 mg • glucose qs 2.5% • sodium hydroxide qsp pH = 4-4.5 5 · waterppi ......................... qsp 20 ml EXAMPLE 2

On prépare selon la technique habituelle une composition liquide destinée à l’usageparentéral comprenant : • acide (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2- 10 thiénylthio)éthyl]pipéridine-3-acétique ........................ 125 mg • glucose qsp 2,5 % • hydroxyde de sodium qsp pH = 4-4,5 • eauppi ......................... qsp 20 ml 286 12 0 2 2A liquid composition for parenteral use comprising: (3R, 4R) -4- [3- (R, S) -hydroxy-3- (6-methoxyquinolin-4-yl) propyl] is prepared according to the usual technique; 1- [2- (2-thienylthio) ethyl] piperidine-3-acetic acid ........................ 125 mg • glucose qs 2, 5% • sodium hydroxide qsp pH = 4-4,5 • waterppi ......................... qs 20 ml 286 12 0 2 2

REVENDICATIONS 1- Un dérivé de quinolyl propyl pipéridine de formule générale :1- A quinolyl propyl piperidine derivative of general formula:

dans laquelle :in which :

Ri est un atome d’hydrogène ou d’halogène, ou un radical hydroxy, R’i est un atome d’hydrogène, ou peut représenter halogène lorsque Ri est égalementun atome d’halogène, et R° est un atome d’hydrogène, ou bienR 1 is a hydrogen or halogen atom, or a hydroxy radical, R 1 is a hydrogen atom, or may represent halogen when R 1 is also a halogen atom, and R 0 is a hydrogen atom, or

Ri et R° forment ensemble une liaison et R’i est un atome d’hydrogène, et soit R2 représente un radical carboxy, cafboxyméthyle ou carboxy-2 éthyle, R3 représente un radical alcoyle (1 à 6 atomes de carbone) substitué par 1 à 3substituants choisis parmi hydroxy, halogène, oxo, carboxy, alcoyloxycarbonylealcoyloxy, alcoylthio ou parmi un radical phényle, phénylthio ouphénylalcoylthio pouvant eux-même porter 1 à 4 substituants [choisis parmihalogène, hydroxy, alcoyle, alcoyloxy, trifluorométhyle, trifluorométhoxy,carboxy, alcoyloxycarbonyle, cyano, acétamido (1 à 4C) ou amino] ou parmi unradical cycloalcoyle ou cycloalcoylthio dont la partie cyclique contient 3 à 7chaînons, ou parmi un radical hétérocyclyle ou hétérocyclylthio aromatique de 5à 6 chaînons comprenant 1 à 4 hétéroatomes choisis parmi l’azote, l’oxygène oule soufre et éventuellement eux-même substitués [par halogène, hydroxy, alcoyle,alcoyloxy, trifluorométhyle, trifluorométhoxy, oxo, carboxy, alcoyloxycarbonyle, *cyano ou amino], ou R3 représente un radical propargyle substitué par un radicalphényle pouvant lui même porter 1 à 4 substituants [choisis parmi halogène,hydroxy, alcoyle, alcoyloxy, trifluorométhyle, trifluorométhoxy, carboxy,^alcoyloxycarbonyle, cyano ou amino], ou substitué par un radical cycloalcoyleR 1 and R 6 together form a bond and R 1 is a hydrogen atom, and either R 2 represents a carboxy, a carboxymethyl or a 2-carboxy ethyl radical, R 3 represents an alkyl radical (1 to 6 carbon atoms) substituted with 1 to 3 substituents selected from hydroxy, halogen, oxo, carboxy, alkyloxycarbonylalkyloxy, alkylthio or from a phenyl, phenylthio or phenylalkylthio radical which can themselves carry 1 to 4 substituents [selected from among halogen, hydroxy, alkyl, alkyloxy, trifluoromethyl, trifluoromethoxy, carboxy, alkyloxycarbonyl, cyano, acetamido (1 to 4C) or amino) or from a cycloalkyl radical or cycloalkylthio whose cyclic portion contains 3 to 7 chaines, or from a 5- to 6-membered aromatic heterocyclyl or heterocyclylthio radical comprising 1 to 4 heteroatoms selected from nitrogen, oxygen or sulfur and optionally themselves substituted [by halogen, hydroxy, alkyl, alkyloxy, trifluoromethyl, trifluoromethoxy, oxo, carboxy, alkyloxycarbonyl, cyano or amino], or R3 represents a propargyl radical substituted with a phenyl radical which can itself carry 1 to 4 substituents [chosen from halogen, hydroxy, alkyl, alkyloxy, trifluoromethyl, trifluoromethoxy, carboxy, alkyloxycarbonyl, cyano or amino], or substituted with a cycloalkyl radical

Claims (11)

287 120 22 contenant 3 à 7 chaînons ou substitué par un radical hétérocyclyle aromatique de5 à 6 chaînons comprenant 1 à 4 hétéroatomes choisis parmi l’azote, l’oxygèneou le soufre et éventuellement lui-même substitué [par halogène, hydroxy,alcoyle, alcoyloxy, trifluorométhyle, trifluorométhoxy, oxo, carboxy,alcoyloxycarbonyle, cyano ou amino], ou R3 représente cinnamyle ou 4-phénylbutèn-3-yle, et R4 représente un radical alcényl-CHî- ou alcynyl-CH2- dont les parties alcényle oualcynyle contiennent 2 à 6 atomes de carbone, soit R2 représente un radical carboxy, carboxyméthyle ou carboxy-2 éthyle, et R3 représente un radical alcoyle (1 à 6· atomes de carbone) substitué par 1 à 3substituants choisis parmi halogène, oxo, carboxy, alcoyloxycarbonyle,alcoylthio ou parmi un radical phénylthio ou phénylalcoylthio pouvant eux-mêmeporter 1 à 4 substituants [choisis parmi halogène, hydroxy, alcoyle, alcoyloxy,trifluorométhyle, trifluorométhoxy, carboxy, alcoyloxycarbonyle, cyano,acétamido (là 4C) ou amino J ou parmi un radical cycloalcoylthio dont la partiecyclique contient 3 à 7 chaînons, ou parmi un radical hétérocyclylthio aromatiquede 5 à 6 chaînons comprenant 1 à 4 hétéroatomes choisis parmi l’azote,l’oxygène ou le soufre et éventuellement eux-même substitués [par halogène,hydroxy, alcoyle, alcoyloxy, trifluorométhyle, trifluorométhoxy, oxo, carboxy,alcoyloxycarbonyle, cyano ou amino], ou R3 représente un radical propargylesubstitué par un radical phényle pouvant lui même porter 1 à 4 substituants[choisis parmi halogène, hydroxy, alcoyle, alcoyloxy, trifluorométhyle,trifluorométhoxy, carboxy, alcoyloxycarbonyle, cyano ou amino], ou substituépar un radical cycloalcoyle contenant 3 à 7 chaînons ou substitué par un radicalhétérocyclyle aromatique de 5 à 6 chaînons comprenant 1 à 4 hétéroatomeschoisis parmi l’azote, l’oxygène ou le soufre et éventuellement lui-mêmesubstitué [par halogène, hydroxy, alcoyle, alcoyloxy, trifluorométhyle,trifluorométhoxy, oxo, carboxy, alcoyloxycarbonyle, cyano ou amino], et R4 représente un radical alcoyle (contenant 1 à 6 atomes de carbone), ou bien R2 représente un radical hydroxyméthyîe, alcoyloxycarbonyle,alcoyloxycarbonylméthyle ou alcoyloxycarbonyl-2-éthyle (dont les partiesalcoyle contiennent 1 à 6C) et 288 120 2 2 R-3 représente un radical alcoyle (1 à 6 atonies de carbone) substitué par un radicalphénylthio pouvant lui même porter 1 à 4 substituants [choisis parmi halogène,hydroxy, alcoyle, alcoyloxy, trifluorométhyle, trifluorométhoxy, carboxy,alcoyloxycarbonyle, cyano ou amino], par un radical cycloalcoylthio dont lapartie cyclique contient 3 à 7 chaînons, ou par un radical hétérocyclylthioaromatique de 5 à 6 chaînons comprenant 1 à 4 hétéroatomes choisis parmil’azote, l’oxygène ou le soufre et éventuellement lui même substitué [parhalogène, hydroxy, alcoyle, alcoyloxy, trifluorométhyle, trifluorométhoxy, oxo,carboxy, alcoyloxycarbonyle, cyano ou amino] ou R3 représente un radicalpropargyle substitué par un radical phényle pouvant lui même porter 1 à 4substituants [choisis parmi halogène, hydroxy, alcoyle, alcoyloxy,trifluorométhyle, trifluorométhoxy, carboxy, alcoyloxycarbonyle, cyano ouamino], ou substitué par un radical cycloalcoyle contenant 3 à 7 chaînons ousubstitué par un radical hétérocyclyle aromatique de 5 à 6 chaînons comprenant 1à 4 hétéroatomes choisis parmi l’azote, l’oxygène ou le soufre et éventuellementlui-même substitué [par halogène, hydroxy, alcoyle, alcoyloxy, trifluorométhyle,trifluorométhoxy, oxo, carboxy, alcoyloxycarbonyle, cyano ou amino], et R4 représente un radical alcoyle (contenant 1 à 6 atomes de carbone), alcényl-CH2-ou alcynyl-CHî- dont les parties alcényle ou alcynyle contiennent 2 à 6 atomes decarbone, étant entendu que les radicaux et portions alcoyle sont en en chaîne droite ou ramifiéeet contiennent, sauf mention spéciale, 1 à 4 atomes de carbone, sous ses formes diastéréoisomères ou leurs mélanges, ainsi que ses sels.287 120 22 containing 3 to 7-membered or substituted with a 5- to 6-membered aromatic heterocyclyl radical having 1 to 4 heteroatoms selected from nitrogen, oxygen or sulfur and optionally itself substituted [by halogen, hydroxy, alkyl, alkyloxy] , trifluoromethyl, trifluoromethoxy, oxo, carboxy, alkyloxycarbonyl, cyano or amino], or R3 represents cinnamyl or 4-phenylbuten-3-yl, and R4 represents alkenyl-CH1- or alkynyl-CH2- whose alkenyl or alkynyl parts contain 2 to 6 carbon atoms, either R2 represents a carboxy, carboxymethyl or 2-carboxy ethyl radical, and R3 represents an alkyl radical (1 to 6 · carbon atoms) substituted with 1 to 3 substituents selected from halogen, oxo, carboxy, alkyloxycarbonyl, alkylthio or from a phenylthio or phenylalkylthio radical which can themselves carry 1 to 4 substituents [selected from halogen, hydroxy, alkyl, alkyloxy, trifluoromethyl, trifluoromethoxy, carbox y, alkyloxycarbonyl, cyano, acetamido (4C) or amino, or from a cycloalkylthio radical having 3 to 7 membered cycloalkyl, or from a 5- to 6-membered aromatic heterocyclylthio radical having 1 to 4 heteroatoms selected from nitrogen, oxygen or sulfur and optionally themselves substituted [by halogen, hydroxy, alkyl, alkyloxy, trifluoromethyl, trifluoromethoxy, oxo, carboxy, alkyloxycarbonyl, cyano or amino], or R3 represents a propargyl radical substituted by a phenyl radical which can itself carry 1 to 4 substituents [selected from halogen, hydroxy, alkyl, alkyloxy, trifluoromethyl, trifluoromethoxy, carboxy, alkyloxycarbonyl, cyano or amino], or substituted with a 3- to 7-membered cycloalkyl radical or substituted with a 5- to 6-membered aromatic heterocyclyl radical comprising 1 to 4 heteroatoms selected from nitrogen, oxygen or sulfur and optionally itself substituted [by hal ogen, hydroxy, alkyl, alkyloxy, trifluoromethyl, trifluoromethoxy, oxo, carboxy, alkyloxycarbonyl, cyano or amino], and R4 represents an alkyl radical (containing 1 to 6 carbon atoms), or R2 represents a hydroxymethyl, alkyloxycarbonyl or alkyloxycarbonylmethyl radical; or alkyloxycarbonyl-2-ethyl (the alkyl portions of which contain 1 to 6C) and R-3 represents an alkyl radical (1 to 6 carbon atoms) substituted by a phenylthio radical which can itself carry 1 to 4 substituents [chosen from halogen, hydroxy, alkyl, alkyloxy, trifluoromethyl, trifluoromethoxy, carboxy, alkyloxycarbonyl, cyano or amino], with a cycloalkylthio radical whose cyclic part contains 3 to 7 members, or with a 5- to 6-membered heterocyclylthioaromatic radical comprising 1 to 4 selected heteroatoms Nitrogen, oxygen or sulfur and possibly itself substituted [parhalogen, hydroxy, alkyl, alkyloxy, trifluorometh yl, trifluoromethoxy, oxo, carboxy, alkyloxycarbonyl, cyano or amino] or R3 represents a propargyl radical substituted with a phenyl radical which can itself carry 1 to 4 substitutents [selected from halogen, hydroxy, alkyl, alkyloxy, trifluoromethyl, trifluoromethoxy, carboxy, alkyloxycarbonyl, cyanoamino], or substituted with a 3- to 7-membered cycloalkyl radical or substituted with a 5- to 6-membered aromatic heterocyclyl radical comprising 1 to 4 heteroatoms selected from nitrogen, oxygen or sulfur and optionally itself substituted [by halogen hydroxy, alkyl, alkyloxy, trifluoromethyl, trifluoromethoxy, oxo, carboxy, alkyloxycarbonyl, cyano or amino], and R4 represents an alkyl radical (containing 1 to 6 carbon atoms), alkenyl-CH2-or alkynyl-CH1- whose parts alkenyl or alkynyl contain 2 to 6 carbon atoms, it being understood that the radicals and alkyl portions are in straight or branched chain and contain, unless otherwise stated, 1 to 4 carbon atoms, in its diastereoisomeric forms or mixtures thereof, and salts thereof. 2- Un dérivé de quinolyl propyl pipéridine selon la revendication 1, caractérisé ence que Ri est un atome d’hydrogène ou d’halogène, ou un radical hydroxy, R’ 1 est un atome d’hydrogène, et R° est un atome d’hydrogène, ou bien Ri et R° forment ensemble une liaison et R’ 1 est un atome d’hydrogène, R2 représente un radical carboxy ou carboxyméthyle, et 120 22 289 R-3 représente un radical alcoyle (1 à 6 atomes de carbone) substitué par 1 à 3substituants choisis parmi halogène, oxo, , alcoylthio ou parmi un radicalphénylthio pouvant eux-même porter 1 à 4 atomes d'halogène ou parmi unradical cycloalcoylthio dont la partie cyclique contient 3 à 7 chaînons, ou parmiun radical hétérocyclyîthio aromatique de 5 à 6 chaînons comprenant 1 à 4hétéroatomes choisis parmi l’azote, l’oxygène ou le soufre et éventuellementeux-même substitués par halogène, ou R3 représente un radical propargylesubstitué par un radical phényle pouvant lui même porter 1 à 3 substituantshalogène, ou propargyle substitué par un radical hétérocyclyle aromatique de 5 à6 chaînons comprenant 1 à 4 hétéroatomes choisis parmi l’azote, l’oxygène ou lesoufre, ou bien R2 représente un radical hydroxyméîhyle, alcoyloxycarbonyle ou alcoyloxycarbonyl-. méthyle (dont les portions alcoyle contiennent 1 à 6 atomes de carbone) et R3 représente un radical alcoyle (1 à 6 atomes de carbone) substitué par un radicalhétérocyclyîthio aromatique de 5 à 6 chaînons comprenant 1 à 4 hétéroatomeschoisis parmi l’azote, l’oxygène ou le soufre ou R3 représente un radicalpropargyle substitué par un radical hétérocyclyle aromatique de 5 à 6 chaînonscomprenant 1 à 4 hétéroatomes choisis parmi l’azote, l’oxygène ou le soufre,et R4 représente un radical alcoyle (contenant 1 à 6 atomes de carbone), les radicaux et portions alcoyle étant en en chaîne droite ou ramifiée, sous scs formes diastcréoisomères ou leurs mélanges, ainsi que ses sels.2- A quinolyl propyl piperidine derivative according to claim 1, characterized in that R1 is a hydrogen or halogen atom, or a hydroxy radical, R '1 is a hydrogen atom, and R ° is a hydrogen atom. hydrogen, or R 1 and R 6 together form a bond and R 1 is a hydrogen atom, R 2 represents a carboxy or carboxymethyl radical, and R-3 represents an alkyl radical (1 to 6 carbon atoms ) substituted with 1 to 3 substituents selected from halogen, oxo, alkylthio or from a phenylthio radical which may themselves carry 1 to 4 halogen atoms or from a radical cycloalkylthio whose ring part contains 3 to 7 ring members, or from an aromatic heterocyclylthio radical of 5- to 6-membered group comprising 1 to 4 heteroatoms selected from nitrogen, oxygen or sulfur and optionally even substituted by halogen, or R3 represents a propargyl radical substituted by a phenyl radical which may itself 1 to 3 substituents halogen, or propargyl substituted with a 5- to 6-membered aromatic heterocyclyl radical having 1 to 4 heteroatoms selected from nitrogen, oxygen or sulfur, or R2 is hydroxymethyl, alkyloxycarbonyl or alkyloxycarbonyl. methyl (the alkyl portions of which contain 1 to 6 carbon atoms) and R3 represents an alkyl radical (1 to 6 carbon atoms) substituted by a 5- to 6-membered aromatic heterocyclylthio radical having 1 to 4 heteroatoms selected from nitrogen, oxygen or sulfur or R3 represents a propargyl radical substituted with a 5- to 6-membered aromatic heterocyclyl radicalcomprising 1 to 4 heteroatoms selected from nitrogen, oxygen or sulfur, and R4 represents an alkyl radical (containing 1 to 6 carbon atoms); carbon), the radicals and alkyl portions being in straight or branched chain, in diastreoisomeric forms or mixtures thereof, as well as its salts. 3- Un dérivé de quinolyl propyl pipéridine selon l'une des revendications 1 ou 2,caractérisé en ce qu’il s'agit de l'acide (3R,4R)-4-[3-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[2-(2-thiénylthio)éthyI]pipéridine-3-acétique,sous ses formes diastéréoisomères ou leurs mélanges, ainsi que ses sels.3- A quinolylpropylpiperidine derivative according to one of claims 1 or 2, characterized in that it is (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolinic acid) 4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-acetic acid, in its diastereoisomeric forms or mixtures thereof, and its salts. 4- Un dérivé de quinolyl propyl pipéridine selon l'une des revendications 1 ou 2,caractérisé en ce qu'il s'agit de l'acide (3R,4R)~4-[3-(6-méthoxyquinolin-4-yI)propyl]-l-[2-(2-thiénylthio)éthyl] pipéridine-3-acétique, ainsi que ses sels.4- A quinolylpropylpiperidine derivative according to one of claims 1 or 2, characterized in that it is acid (3R, 4R) ~ 4- [3- (6-methoxyquinolin-4-yl) ) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-acetic acid, and its salts. 5- Un dérivé de quinolyl propyl pipéridine selon l'une des revendications 1 ou 2,caractérisé en ce qu'il s’agit de l'acide (3R,4R)-4-[3-fluoro-3-(6-méthoxyquinolin- 4-yl)propyl]-l-[2-(2-thiénylthio)éthyl]pipéridine-3-acétique, sous ses formesdiastéréoisomères ou leurs mélanges, ainsi que ses sels. 290 120225 - A quinolylpropylpiperidine derivative according to one of claims 1 or 2, characterized in that it is (3R, 4R) -4- [3-fluoro-3- (6-methoxyquinolinic acid) 4-yl) propyl] -1- [2- (2-thienylthio) ethyl] piperidine-3-acetic acid, in its diastereoisomeric forms or mixtures thereof, and its salts. 290 12022 6- Un dérivé de quinolyl propyl pipéridine selon l'une des revendications 1 ou 2,caractérisé en ce qu'il s'agit de l'acide (3R,4R)-l-[2-(3-fluorophénylthio)éthyl]-4-[3 -hy droxy-3 -(6-méthoxyquinolin-4-yl)propyl]pipéridine-3 -acétique, sous sesformes diastéréoisomères ou leurs mélanges, ainsi que ses sels.6- A quinolylpropylpiperidine derivative according to one of claims 1 or 2, characterized in that it is (3R, 4R) -1- [2- (3-fluorophenylthio) ethyl] - 4- [3-hydroxy-3- (6-methoxyquinolin-4-yl) propyl] piperidine-3-acetic acid, in diastereoisomeric forms or mixtures thereof, and salts thereof. 7- Un dérivé de quinolyl propyl pipéridine selon l'une des revendications 1 ou 2, caractérisé en ce qu'il s'agit de l'acide (3R,4R)-4-[3-hydroxy-3-(6-méthoxyquinolin-4-yl)propyl]-l-[3-(2,3,5-trifluorophényl)prop-2- ynyl]pipéridine-3-carboxylique, sous ses formes diastéréoisomères ou leursmélanges, ainsi que ses sels.7- A quinolylpropylpiperidine derivative according to one of claims 1 or 2, characterized in that it is (3R, 4R) -4- [3-hydroxy-3- (6-methoxyquinolinic acid) 4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] piperidine-3-carboxylic acid, in its diastereoisomeric forms or mixtures thereof, and salts thereof. 8- Un procédé de préparation de dérivé de quinolyl propyl pipéridine selon la revendication 1, caractérisé en ce que l’on condense la chaîne R3 définie dans larevendication 1, sur le dérivé de quinolyl propyl pipéridine de formule générale :8- A process for preparing a quinolylpropylpiperidine derivative according to claim 1, characterized in that the R3 chain defined in claim 1 is condensed on the quinolylpropylpiperidine derivative of general formula: dans laquelle R4 est défini commedans la revendication 1, R"i et R"’i représentent des15 atomes d’hydrogène ou forment ensemble un radical oxo et R’2 représente un radical carboxy, carboxyméthyle ou carboxy-2 éthyle protégés, ou un radicalalcoyloxycarbonyle, alcoyloxycarbonylméthyle ou alcoyloxycarbonyl-2-éthyle, pour obtenir un dérivé de quinolyl propyl pipéridine de formule générale :wherein R 4 is defined in claim 1, R 1 and R "1 represent hydrogen atoms or together form an oxo radical and R '2 represents a protected carboxy, carboxymethyl or carboxy-2 ethyl radical, or a radicalalkyloxycarbonyl , alkyloxycarbonylmethyl or alkyloxycarbonyl-2-ethyl, to obtain a quinolylpropylpiperidine derivative of general formula: 20 pour lequel R"i, R"’i, R’2 et R4 sont définis comme ci-dessus et R3 est défini commedans la revendication 1, puis élimine le cas échéant le radical protecteur d'acide, 120 22 291 ou bien, le cas échéant réduit le radical oxo représenté par R"i et R"’i en un alcoolpour lequel Ri représente hydroxy puis éventuellement effectue l'halogénation sil’on veut obtenir un dérivé de quinolyî propyl pipéridine pour lequel Rj est unatome d’halogène, et éventuellement effectue la déhydrohalogénation du dérivé 5 halogéné correspondant, pour obtenir un dérivé de quinolyî propyl pipéridine pour lequel Ri et R° forment ensemble une liaison, ou bien met en oeuvre ladihalogénation du produit de formule générale (HI) pour lequel R"i et R”’iforment ensemble un radical oxo pour obtenir un dérivé de quinolyî propylpipéridine pour lequel R) et R’j sont des atomes d’halogène, 10 et/ou le cas échéant réduit l’acide protégé sous forme d’un radical R’2 en position -3de la pipéridine, en un radical hydroxyméthyîe et éventuellement transforme enun radical carboxyméthyle ou carboxy-2 éthyle selon les méthodes habituelles, puis éventuellement élimine le radical protecteur d’acide et/ou sépare, le cas échéant,les diastéréoisomères et éventuellement transforme le produit obtenu en un sel.Wherein R "1, R" 'i, R'2 and R4 are defined as above and R3 is as defined in claim 1, then optionally removing the acid protecting group, 120 22 291 or if necessary reduces the oxo radical represented by R "i and R" 'i to an alcohol for which R 1 represents hydroxy and then optionally carries out the halogenation if it is desired to obtain a quinolypropylpiperidine derivative for which R 1 is a halogen atom, and optionally performs the dehydrohalogenation of the corresponding halogenated derivative, to obtain a quinolypropyl piperidine derivative for which R 1 and R 6 together form a bond, or else involves the halogenation of the product of the general formula (III) for which R "i and R & D together an oxo radical to obtain a quinolypropylpiperidine derivative for which R) and R'j are halogen atoms, and / or where appropriate reduced the protected acid as a radica R'2 in the position -3 of piperidine, a hydroxyméthyîe radical and optionally converted to a carboxymethyl or 2-carboxy ethyl by the usual methods, then optionally eliminates the acid-protecting radical and / or separates, where appropriate, the diastereoisomers and optionally converts the product obtained into a salt. 9- Un procédé selon la revendication 2, caractérisé en ce que la condensation de la chaîne R3 sur la pipéridine s’effectue par action d’un dérivé de formule générale : Rj-X dans laquelle R3 est défini comme précédemment et X représente un atomed’halogène, un radical méthyîsulfonyîe, tm radical trïfluorométhylsulfonyle ou 20 p.toluènesulfonyle.9- A method according to claim 2, characterized in that the condensation of the R3 chain on the piperidine is carried out by action of a derivative of general formula: Rj-X wherein R3 is defined as above and X represents an atomed halogen, a methylsulfonyl radical, a trifluoromethylsulfonyl radical or a p-toluenesulfonyl radical. 10- Un procédé selon l’une des revendications 2 ou 3, caractérisé en ce que lorsqueR3 représente propargyle substitué par phényle, cycioalcoyle ou hétérocyclyle, laréaction s'effectue de préférence par condensation d'un halogénure de propargyle,puis substitution de la chaîne par un radical phényle, cycioalcoyle ou 25 hétérocyclyle.10- A process according to one of claims 2 or 3, characterized in that when R3 represents propargyl substituted with phenyl, cycloalkyl or heterocyclyl, the reaction is preferably carried out by condensation of a propargyl halide and then substitution of the chain by a phenyl, cycloalkyl or heterocyclyl radical. 11- Composition pharmaceutique caractérisée en ce qu'elle contient au moins un dé-rivé selon la revendication 1, à l'état pur ou en association avec un ou plusieursdiluants ou adjuvants compatibles et pharmaceutiquement acceptables.11. A pharmaceutical composition characterized in that it contains at least one derivative according to claim 1, in the pure form or in combination with one or more compatible and pharmaceutically acceptable diluents or adjuvants. / fi // fi /
OA1200200074A 1999-09-17 2000-09-14 Quinolyl propyl piperidine derivatives and their use as antibacterials. OA12022A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
FR9911679A FR2798656B1 (en) 1999-09-17 1999-09-17 DERIVATIVES OF QUINOLYL PROPYL PIPERIDINE, THEIR PREPARATION AND THE COMPOSITIONS CONTAINING THEM

Publications (1)

Publication Number Publication Date
OA12022A true OA12022A (en) 2006-04-19

Family

ID=9549990

Family Applications (1)

Application Number Title Priority Date Filing Date
OA1200200074A OA12022A (en) 1999-09-17 2000-09-14 Quinolyl propyl piperidine derivatives and their use as antibacterials.

Country Status (30)

Country Link
EP (2) EP1484328B1 (en)
JP (1) JP2004527448A (en)
KR (1) KR20020038757A (en)
CN (1) CN1374959A (en)
AP (1) AP2002002459A0 (en)
AT (1) ATE284399T1 (en)
AU (1) AU7429500A (en)
BG (1) BG106524A (en)
BR (1) BR0014060A (en)
CA (1) CA2383836A1 (en)
CZ (1) CZ2002940A3 (en)
DE (2) DE60034713T2 (en)
DZ (1) DZ3195A1 (en)
EA (1) EA005183B1 (en)
EE (1) EE200200138A (en)
FR (1) FR2798656B1 (en)
GE (1) GEP20043223B (en)
HR (1) HRP20020214A2 (en)
HU (1) HUP0204283A3 (en)
IL (1) IL148720A0 (en)
MA (1) MA26820A1 (en)
MX (1) MXPA02001979A (en)
NO (1) NO20021253L (en)
OA (1) OA12022A (en)
PL (1) PL354809A1 (en)
SK (1) SK3632002A3 (en)
TN (1) TNSN00184A1 (en)
WO (1) WO2001025227A2 (en)
YU (1) YU19002A (en)
ZA (1) ZA200202073B (en)

Families Citing this family (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9822440D0 (en) 1998-10-14 1998-12-09 Smithkline Beecham Plc Medicaments
GB9917408D0 (en) 1999-07-23 1999-09-22 Smithkline Beecham Plc Compounds
GB9917406D0 (en) 1999-07-23 1999-09-22 Smithkline Beecham Plc Compounds
DE60125373T2 (en) 2000-07-26 2007-10-18 Smithkline Beecham P.L.C., Brentford AMINOPIPERIDINE CHINOLINE AND ITS AZAISOSTERIC ANALOGUE WITH ANTIBACTERIAL EFFECT
GB0031086D0 (en) * 2000-12-20 2001-01-31 Smithkline Beecham Plc Medicaments
GB0101577D0 (en) 2001-01-22 2001-03-07 Smithkline Beecham Plc Compounds
GB0112834D0 (en) 2001-05-25 2001-07-18 Smithkline Beecham Plc Medicaments
GB0112836D0 (en) 2001-05-25 2001-07-18 Smithkline Beecham Plc Medicaments
WO2003064431A2 (en) 2002-01-29 2003-08-07 Glaxo Group Limited Aminopiperidine compounds, process for their preparation, and pharmaceutical compositions containing them
EP2181996A1 (en) 2002-01-29 2010-05-05 Glaxo Group Limited Aminopiperidine derivatives
AR040335A1 (en) 2002-06-26 2005-03-30 Glaxo Group Ltd CYCLLOHEXAN OR CYCLHEXENE COMPOUND, USE OF THE SAME TO PREPARE A MEDICINAL PRODUCT, PHARMACEUTICAL COMPOSITION THAT INCLUDES IT, PROCEDURE AND INTERMEDIATE COMPOUNDS OF UTILITY TO PREPARE SUCH COMPOUND
AR040336A1 (en) 2002-06-26 2005-03-30 Glaxo Group Ltd PIPERIDINE COMPOUND, USE OF THE SAME FOR THE MANUFACTURE OF A MEDICINAL PRODUCT, PHARMACEUTICAL COMPOSITION THAT INCLUDES IT AND PROCEDURE TO PREPARE SUCH COMPOUND
FR2842807A1 (en) * 2002-07-23 2004-01-30 Aventis Pharma Sa QUINOLYL PROPYL PIPERIDINE DERIVATIVES, PROCESS AND PREPARATION INTERMEDIATES AND COMPOSITIONS COMPRISING THE SAME
FR2844270B1 (en) 2002-09-11 2006-05-19 Aventis Pharma Sa QUINOLYL PROPYL PIPERIDINE DERIVATIVES, THEIR PROCESS AND PREPARATION INTERMEDIATES AND THE COMPOSITIONS CONTAINING THEM
FR2844268B1 (en) 2002-09-11 2004-10-22 Aventis Pharma Sa QUINOLYL PROPYL PIPERIDINE DERIVATIVES, PROCESSES AND INTERMEDIATES FOR THEIR PREPARATION, AND COMPOSITIONS CONTAINING THEM
CA2500320A1 (en) * 2002-10-10 2004-04-29 Morphochem Aktiengesellschaft Fuer Kombinatorische Chemie Novel compounds with antibacterial activity
JP4704755B2 (en) 2002-11-05 2011-06-22 グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー Antibacterial agent
DE60334016D1 (en) 2002-11-05 2010-10-14 Glaxo Group Ltd ANTIBACTERIAL AGENTS
EP1567520B1 (en) 2002-12-04 2008-10-15 Glaxo Group Limited Quinolines and nitrogenated derivatives thereof and their use as antibacterial agents
EP1799674B1 (en) * 2004-10-05 2010-05-05 Actelion Pharmaceuticals Ltd. New piperidine antibiotics
CN101039935B (en) * 2004-10-05 2011-04-20 埃科特莱茵药品有限公司 New piperidine antibiotics
JP2008528587A (en) 2005-01-25 2008-07-31 グラクソ グループ リミテッド Antibacterial agent
EP1846418A4 (en) 2005-01-25 2009-12-23 Glaxo Group Ltd Antibacterial agents
WO2006081178A2 (en) 2005-01-25 2006-08-03 Glaxo Group Limited Antibacterial agents
US7605169B2 (en) 2005-01-25 2009-10-20 Glaxo Group Limited Antibacterial agents
CA2635126A1 (en) 2006-01-26 2007-08-02 Actelion Pharmaceuticals Ltd Tetrahydropyrane antibiotics
WO2007115947A1 (en) 2006-04-06 2007-10-18 Glaxo Group Limited Pyrrolo-quinoxalinone derivatives as antibacterials
GB0613208D0 (en) 2006-07-03 2006-08-09 Glaxo Group Ltd Compounds
EP1992628A1 (en) 2007-05-18 2008-11-19 Glaxo Group Limited Derivatives and analogs of N-ethylquinolones and N-ethylazaquinolones
WO2008139288A2 (en) * 2007-05-09 2008-11-20 Pfizer Inc. Substituted heterocyclic derivatives and compositions and their pharmaceutical use as antibacterials
EP2080761A1 (en) 2008-01-18 2009-07-22 Glaxo Group Limited Compounds
WO2010043714A1 (en) 2008-10-17 2010-04-22 Glaxo Group Limited Tricyclic nitrogen compounds used as antibacterials
EP2379554B1 (en) 2009-01-15 2015-11-11 Glaxo Group Limited Naphthyridin-2(1h)-one compounds useful as antibacterials
CN105636945B (en) * 2013-10-14 2017-11-17 卫材R&D管理有限公司 The quinoline compound selectively substituted
EA031589B1 (en) 2014-08-22 2019-01-31 Глэксосмитклайн Интеллекчуал Проперти Дивелопмент Лимитед Tricyclic nitrogen containing compounds for treating neisseria gonorrhoea infection
UY36851A (en) 2015-08-16 2017-03-31 Glaxosmithkline Ip Dev Ltd COMPOUNDS FOR USE IN ANTIBACTERIAL APPLICATIONS
KR20180094939A (en) 2015-12-17 2018-08-24 메르크 파텐트 게엠베하 Polycyclic TLR7 / 8 antagonists and their use in the treatment of immune disorders
SG11201900947RA (en) 2016-08-08 2019-02-27 Merck Patent Gmbh Tlr7/8 antagonists and uses thereof

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2201674T3 (en) * 1998-01-26 2004-03-16 Smithkline Beecham Plc DERIVATIVES OF QUINOLINA WITH ANTIBACTERIAL PROPERTIES.
AU2437900A (en) * 1999-01-20 2000-08-07 Smithkline Beecham Plc Piperidinylquinolines as protein tyrosine kinase inhibitors

Also Published As

Publication number Publication date
EP1484328A1 (en) 2004-12-08
PL354809A1 (en) 2004-02-23
TNSN00184A1 (en) 2005-11-10
EA005183B1 (en) 2004-12-30
CN1374959A (en) 2002-10-16
NO20021253D0 (en) 2002-03-13
EP1218370B1 (en) 2004-12-08
BG106524A (en) 2003-01-31
WO2001025227A2 (en) 2001-04-12
EA200200374A1 (en) 2002-10-31
MXPA02001979A (en) 2002-08-20
MA26820A1 (en) 2004-12-20
YU19002A (en) 2005-06-10
DE60016611D1 (en) 2005-01-13
AU7429500A (en) 2001-05-10
ATE284399T1 (en) 2004-12-15
IL148720A0 (en) 2002-09-12
NO20021253L (en) 2002-04-24
BR0014060A (en) 2002-05-21
SK3632002A3 (en) 2003-04-01
HRP20020214A2 (en) 2005-04-30
GEP20043223B (en) 2004-04-26
DE60034713T2 (en) 2008-01-17
FR2798656B1 (en) 2004-12-17
WO2001025227A3 (en) 2001-11-22
AP2002002459A0 (en) 2002-06-30
KR20020038757A (en) 2002-05-23
EP1218370A2 (en) 2002-07-03
HUP0204283A3 (en) 2004-07-28
EP1484328B1 (en) 2007-05-02
ZA200202073B (en) 2003-08-27
EE200200138A (en) 2003-06-16
JP2004527448A (en) 2004-09-09
CA2383836A1 (en) 2001-04-12
CZ2002940A3 (en) 2002-07-17
DZ3195A1 (en) 2001-04-12
DE60034713D1 (en) 2007-06-14
DE60016611T2 (en) 2005-12-22
HUP0204283A2 (en) 2003-04-28
FR2798656A1 (en) 2001-03-23

Similar Documents

Publication Publication Date Title
OA12022A (en) Quinolyl propyl piperidine derivatives and their use as antibacterials.
US6403610B1 (en) Quinolylpropylpiperidine derivatives, their preparation and the compositions which comprise them
EP1337529B1 (en) Heterocyclylalkyl piperidine derivatives, their preparation and compositions containing same
US6602884B2 (en) Quinolylpropylpiperidine derivatives, their preparation, and compositions containing them
EP1542988B1 (en) Piperidine quinolyl propyl derivatives, preparation method and intermediates and compositions containing same
EP1370550B1 (en) Quinolyl propyl piperidine derivatives, the preparation thereof and compositions containing same
EP1539734B1 (en) Piperidine quinolyl propyl derivatives and use thereof as antimicrobial agents
CA2637024C (en) Substituted imidazole derivatives, compositions, and methods of use as ptpase inhibitors
JP5693591B2 (en) Piperidine compounds that inhibit prostaglandin D synthase
WO2009106967A1 (en) Novel 7-substituted derivatives of 3-carboxy-oxadiazino-quinolones, preparation thereof and use thereof as anti-bacterial agents
TW202409010A (en) Inhibitors of human respiratory syncytial virus and metapneumovirus