WO1997010207A1 - Nouveaux derives de benzamide - Google Patents

Nouveaux derives de benzamide Download PDF

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Publication number
WO1997010207A1
WO1997010207A1 PCT/JP1996/002605 JP9602605W WO9710207A1 WO 1997010207 A1 WO1997010207 A1 WO 1997010207A1 JP 9602605 W JP9602605 W JP 9602605W WO 9710207 A1 WO9710207 A1 WO 9710207A1
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WO
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Prior art keywords
integer
group
lower alkyl
alkyl group
hydrogen atom
Prior art date
Application number
PCT/JP1996/002605
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English (en)
Japanese (ja)
Inventor
Masanori Takadoi
Fumiyoshi Kobayashi
Haruo Sekiguchi
Original Assignee
Kyorin Pharmaceutical Co., Ltd.
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 Kyorin Pharmaceutical Co., Ltd. filed Critical Kyorin Pharmaceutical Co., Ltd.
Priority to AU69445/96A priority Critical patent/AU6944596A/en
Publication of WO1997010207A1 publication Critical patent/WO1997010207A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D211/56—Nitrogen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention provides a benzamide derivative and a pharmacologically acceptable acid addition salt having both 5-HT stimulatory action and direct action on gastrointestinal smooth muscle, a process for producing the same, and a gastrointestinal motility regulator containing them as active ingredients.
  • a benzamide derivative and a pharmacologically acceptable acid addition salt having both 5-HT stimulatory action and direct action on gastrointestinal smooth muscle, a process for producing the same, and a gastrointestinal motility regulator containing them as active ingredients.
  • 5-II Tj serotonin receptors
  • 5-II Tj serotonin receptors
  • 5- ⁇ 2 5- ⁇ 2
  • 5- ⁇ 3 5- It is classified as a ⁇ 4 receptor.
  • 5-II ⁇ 4 receptors are widely distributed in the central and peripheral nervous systems, as well as in the digestive system. It is known that the liberation indirectly promotes gastrointestinal motility.
  • An object of the present invention is to provide a 5- HT4 stimulating action and a direct action on gastrointestinal smooth muscle in consideration of the current state of gastrointestinal motility regulators that provide only insufficient clinical effects.
  • the object of the present invention is to provide a gastrointestinal motility regulator that is highly safe and has both of these points.
  • A is (CH 2 )
  • m is an integer from 1 to 3
  • n is an integer from 0 to 2
  • p is an integer from 0 to 3
  • q is an integer from 1 to 3
  • r is is an integer from 0 to 2
  • s is an integer from 2 to 4
  • lower alkyl includes linear or branched C 1-6 alkyl such as methyl, ethyl, n-propyl and iso-propyl
  • lower alkoxycarbonyl Examples include those having 1 to 4 carbon atoms such as methoxycarbonyl and ethoxycarbonyl
  • lower acyl includes those having 1 to 4 carbon atoms such as acetyl and propionyl
  • lower alcokyne includes Linear or branched ones having 1 to 4 carbon atoms such as methoxy and ethoxy can be mentioned.
  • protecting group for amino group examples include lower acyl groups such as acetyl and propionyl, lower alkoxycarbonyl groups such as ethoxycarbonyl and lerl-butoquincarbonyl, and benzyl groups.
  • “3 and R5 together form an amino-protecting group” includes, for example, a phthaloyl group and the like.
  • “Acid addition salts” are pharmacologically acceptable salts such as, for example, inorganic acid salts such as hydrochloric-acetic acid, sulfuric acid, and organic acid salts such as citric acid, succinic acid, fumaric acid, maleic acid, tartaric acid, and the like. It is salt.
  • optical isomers may exist, and these optical isomers and mixtures thereof are included in the compound of the present invention. is.
  • the compound of the present invention can be synthesized, for example, by the method shown below.
  • the compound of general formula (I) is a compound represented by the following general formula (111) (wherein R2 is as described above) or a reactive derivative thereof, and the following general formula (11) (wherein R3 , , X, A, m, n, p, q, r, and s are as described above) and the compound represented by benzene, toluene, diethyl ether, tetrahydrofuran, methylene chloride, chloroform, triacid
  • an appropriate solvent such as ethyl or acetonitrile or in the absence of a solvent, if necessary, an inorganic base such as sodium bicarbonate, sodium carbonate, potassium carbonate or sodium hydride.
  • an organic base such as triethylamine, diisopropylethylamine, N-methylmorpholine, or the like.
  • the "reactive derivative" of the compound of formula C1 (111) includes, for example, lower alkyl esters, active esters, acid anhydrides, acid halides (especially acid chlorides) and the like.
  • active esters include p-ditrophenyl ester, 2,4,5-trichlorophenyl ester, pentachlorophenyl ester, cyanomethyl ester, N —Hydroxysuccinimide Ester, N—Hydroxyphthalimide Ester, N—Hydroxyl 5_Norbornene_ 2, 3—Dicarboxyimide Ester, 8—Hydroxyquinoline Ester, 2—Hydroxyphenyl Ester, 2 — hydroxy-4,5-dichlorophenyl ester, 2-hydroxypyridine ester, 2-pyridinethiol ester and the like.
  • Examples of acid anhydrides include symmetrical acid anhydrides and mixed acid anhydrides, and specific examples of mixed acid anhydrides include chloroethyl carbonate, isobutyl chloroethyl carbonate, and benzyl chloroethyl carbonate.
  • N,N'-dicyclohexane carbodiimide (DCC), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide' hydrochloride (EDCI) , N,N'—Lponyldimidazol (CDI) or the like can be reacted in the presence of a condensing agent.
  • a reaction accelerator such as N-hydroxysuccinimide, 1-hydroxybenzotriazol, or the like may be added to cause the reaction.
  • the compound of general formula (IV) (wherein R3 , R4 , X, m, n, p, and q are as described above, and R5 represents a hydrogen atom, an amino group-protecting group, or R3 and R5 together form an amino group. (which may form a protective group), and then with hydrazine hydrate or an inorganic acid such as hydrochloric acid or sulfuric acid in a suitable solvent such as methanol, ethanol or ethyl acetate at 0-150°C.
  • a suitable solvent such as methanol, ethanol or ethyl acetate at 0-150°C.
  • the compound of general formula (1) (wherein R4 , X, A, m, n, p, and q are as described above) can be synthesized by reacting for 1 to 10 hours at . Further, the compound of the general formula (1d) (wherein R4 , X, A, m, n, p and q are as described above) was converted to the following compound (3) (wherein R6 represents a lower alkyl group , Y represents a leaving group) and tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, acetonitrile, ethyl acetate, benzene, methylene chloride, chloroform, etc.
  • an inorganic base such as sodium bicarbonate, sodium carbonate, sodium carbonate or sodium hydride, triethylamine, diisopropylethyl In the presence of an organic base such as amine, N-methylmorpholine, etc.-2! ) to react at 150°C for 1 to 10 hours
  • the "leaving group” as used herein includes, for example, halogen atoms such as fluorine, chlorine, bromine and iodine, p-toluenesulfonyloxy group, methanesulfonyloxy group and the like.
  • the compound of general formula (1d) (wherein R 4 , X, A, m, n, P, and q are as described above) is compound (1) (wherein X, , m, n , p and q are as described above) and compound (6) (wherein A and Y are as described above) were mixed with tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, acetonitrile in a suitable solvent such as ethyl acetate, benzene, methylene chloride, chloroform or the like, or in the absence of a solvent, if necessary sodium bicarbonate, sodium carbonate, sodium carbonate or sodium hydride.
  • a suitable solvent such as ethyl acetate, benzene, methylene chloride, chloroform or the like, or in the absence of a solvent, if necessary sodium bicarbonate, sodium carbonate, sodium carbonate or sodium hydride.
  • the compound (7) In the presence of an inorganic base such as triethylamine, diisopropylethylamine, N-methylmorpholine, or another organic base, the compound (7) (In the formula, R, ⁇ , X, m, n, p, and q are as described above), and then in a suitable solvent such as ethanol, ethyl acetate, water, etc., a suitable solvent such as palladium carbon, platinum oxide, Raney nickel, etc.
  • a suitable solvent such as ethanol, ethyl acetate, water, etc.
  • a suitable solvent such as palladium carbon, platinum oxide, Raney nickel, etc.
  • a borane complex e.g., borane It can also be synthesized by reacting for 1 to 10 hours at 0°C to the boiling point of the solvent in the presence of a reducing agent such as a monohydrofuran complex.
  • compound (2) (formula A is as described above, Y represents a leaving group) is converted to compound (8) (wherein Z represents ⁇ , IIR3 , C02H ) and a suitable solvent such as tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, acetonitrile, ethyl acetate, benzene, methylene chloride and chloroform, or in the absence of a solvent, If necessary, inorganic bases such as sodium bicarbonate, sodium carbonate, sodium carbonate or sodium hydride, triethylamine, diisopropylethylamine, N-methylmorphol.
  • a suitable solvent such as tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, acetonitrile, ethyl acetate, benzene, methylene chloride and chloroform, or in the absence of a solvent, If necessary, inorgan
  • the "reactive derivative" of compound (10) include lower alkyl esters, active esters, acid anhydrides, acid halides (especially acid chlorides) and the like.
  • active esters include p-ditrophenyl ester, 2,4,5-trichlorophenyl ester, pentachlorophenyl ester, cyanomethyl ester, N-hydroxysuccinimide N-Hydroxyphthalimide Ester, N-Hydroquino-5-Norbornene-2,3-Dicarboximide Ester, 8-Hydroxyquinoline Ester, 2-Hydroxyphenyl Ester, 2-Hydroxy -4,5-dichlorophenyl ester, 2-hydroxypyridine ester, 2-pyridinethiol ester and the like.
  • Examples of acid anhydrides include symmetrical acid anhydrides and mixed acid anhydrides, and specific examples of mixed acid anhydrides include chloroethyl carbonate, chloroisobutyl carbonate, chlorobenzyl carbonate Mixed acid anhydrides with chloroalkyl alkyl esters or aralkyl carboxylic acid esters such as cyclophenyl carbonate, mixed acid anhydrides with cyclophenyl carbonates such as phenyl phenyl carbonate, isovaleric acid, Mixed acid anhydrides with alkanoic acids such as bivalic acid can be mentioned.
  • N,N'--dimclohekinylcarbodiimide DCC
  • 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride EDCI
  • N , N'--Carbonyldimidazole CDI
  • reaction accelerators such as N-hydroxysuccinimide and 1-hydroxybenzotriazol may be added for reaction.
  • ordinary etherification conditions are, for example, compound (9) (formula ⁇
  • a suitable solvent such as tel, tetrahydrofuran, methylene chloride, chloroform, ethyl acetate, acetonitrile, or in the absence of a solvent, if necessary, sodium bicarbonate, sodium carbonate, sodium carbonate or hydrogen.
  • n is 1, and p is 0, it can be synthesized, for example, according to the following production method. That is, the compound (12) (in the formula, R 4 and q are as described above) prepared according to JP-A-60-58981, etc. is treated with palladium in a solvent such as ethanol, ethyl acetate, or water. In the presence of a suitable catalyst such as monocarbon, platinum oxide, rhodium-alumina, Raney-nickel, etc., catalytic reduction can be performed under normal pressure to high pressure conditions to convert to compound (1') (in the formula, R and q are as described above). .
  • a suitable catalyst such as monocarbon, platinum oxide, rhodium-alumina, Raney-nickel, etc.
  • a compound represented by the general formula (111) (wherein R ⁇ and R are as described above) or a reactive derivative thereof and a compound (13) (wherein A is as described above, R8 , Rg represents a protective group for the aldehyde group) is converted to amide (14) according to the usual amidation method.
  • the acetyl group is then treated with or without a suitable solvent such as benzene, toluene, diethyl ether, tetrahydrofuran, methylene chloride, chloroform, ethyl acetate, acetonitrile, methanol or ethanol.
  • an acid such as hydrochloric acid, sulfuric acid, acetic acid, p-toluenesulfonic acid, or another catalyst is used to form an aldehyde (15).
  • the reaction is carried out at 20°C to the boiling point of the solvent for 1 to 6 hours, or in a suitable solvent such as ethanol, ethyl acetate, water, etc., palladium-on-carbon, platinum oxide, rhodium.
  • a suitable solvent such as ethanol, ethyl acetate, water, etc., palladium-on-carbon, platinum oxide, rhodium.
  • a suitable catalyst such as alumina or Raney nickel
  • catalytic reduction under normal pressure to high pressure conditions can be reacted for 1 to 6 hours to give the compound of general formula (I).
  • the term "protecting group for aldehyde group” includes, for example, cyclic or non-cyclic acetaryl, cyclic or non-cyclic dithioacetyl, and the like.
  • the compound of general formula (111) (wherein R 2 is as described above) can be prepared according to, for example, ed. Chera.. 34 (2). 616 (1991).
  • a compound in which R t is a hydrogen atom and R 2 is a fluorine atom is a novel compound.
  • the compound of general formula (I) produced by the above production method is isolated and purified by a common purification method such as chromatography, recrystallization, and reprecipitation.
  • the compound of general formula (I) can be obtained in the form of a free base or an acid addition salt depending on the selection of raw material compounds, reaction conditions, treatment conditions, and the like.
  • Acid addition salts can be converted to the free bases by conventional methods, for example, by treatment with a base such as alkali carbonate, alkali hydroxide.
  • a pharmaceutically acceptable acid addition salt is required, and the free base can be treated with an inorganic acid such as hydrochloric acid or an organic acid such as succinic acid in accordance with a conventional method to obtain an acid addition salt. can lead to Best Mode for Carrying Out the Invention
  • the reaction mixture was washed with saturated brine (150 ml), the aqueous layer was extracted with 20 nil of methylene chloride three times, the organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was recrystallized twice to obtain the 1st crystal of the title compound.
  • Examples 2 to 58 were synthesized as shown in Tables 1 to 7.
  • a compound of general formula (IV) was synthesized in the same manner.
  • the EC 50 (M) was calculated by averaging the 2 cases and performing linear regression at 2 points between 50% of the dose-response curve.
  • the effect was calculated by averaging 2 subjects, expressed as the maximum rate of increase in frequency after addition of the drug to active movement in %.
  • Experiments were performed in the presence (32°C) of atopopin (3 x 100 M) and tetrodotoxin ( 100 M), excluding cholinergic and nervous system-mediated responses.
  • Table 10 shows some of the test results of Examples.
  • the novel benzamide derivative according to the present invention can provide a gastrointestinal motility regulator excellent in improving non-ulcer gastrointestinal symptoms.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Hydrogenated Pyridines (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyrrole Compounds (AREA)

Abstract

Cette invention se rapporte à de nouveaux dérivés de benzamide, représentés par la formule générale (I), ou à des sels d'addition d'acide de ces composés, qui sont acceptables sur le plan pharmacologique; à un procédé pour produire ces composés; ainsi qu'à un régulateur d'entérokinésie comprenant de tels composés comme ingrédient actif, qui possède une action de stimulation de 5-HT4 et qui, en outre, agit directement sur les muscles lisses de l'appareil digestif.
PCT/JP1996/002605 1995-09-12 1996-09-12 Nouveaux derives de benzamide WO1997010207A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU69445/96A AU6944596A (en) 1995-09-12 1996-09-12 Novel benzamide derivatives

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP7259319A JPH0977742A (ja) 1995-09-12 1995-09-12 新規なベンズアミド誘導体
JP7/259319 1995-09-12

Publications (1)

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WO1997010207A1 true WO1997010207A1 (fr) 1997-03-20

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JP (1) JPH0977742A (fr)
AU (1) AU6944596A (fr)
WO (1) WO1997010207A1 (fr)

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2786179A1 (fr) * 1998-11-20 2000-05-26 Hoffmann La Roche Composes quaternaires de piperidine antagonistes du recepteur ccr-3, composition pharmaceutique les contenant, leur utilisation et leur preparation
EP1072596A3 (fr) * 1999-05-28 2001-02-14 Pfizer Inc. Dérivés de 4-arylpipéridine pour le traitement du prurit
WO2001014333A1 (fr) * 1999-08-24 2001-03-01 Astrazeneca Uk Limited Composes de piperidine substitues utiles comme modulateurs de l'activite de recepteurs de chimiokine
US6323223B1 (en) 1997-08-18 2001-11-27 Syntex (U.S.A.) Llc Cyclic amine derivatives- CCR-3 receptor antagonists
WO2002020484A1 (fr) * 2000-09-04 2002-03-14 Astrazeneca Ab Composes chimiques
WO2004002948A1 (fr) * 2001-05-16 2004-01-08 Mitsubishi Pharma Corporation Compose amide et utilisation medicinale de ce compose
US6770650B2 (en) 1997-08-18 2004-08-03 Syntex (U.S.A.) Llc Cyclic amine derivatives-CCR-3 receptor antagonists
US6958350B2 (en) 2001-02-19 2005-10-25 Astrazeneca Ab Chemical compounds
US6960602B2 (en) 2001-03-22 2005-11-01 Astrazeneca Ab Piperidine derivatives as modulators of chemokine receptors
US7192973B2 (en) 2001-11-15 2007-03-20 Astrazeneca Ab Piperidine derivatives and their use as modulators of chemokine receptor activity (especially CCR5)
US7265227B2 (en) 2001-07-23 2007-09-04 Astrazeneca Ab Piperidine derivatives useful as modulators of chemokine receptor activity
US7294636B2 (en) 2003-05-09 2007-11-13 Astrazeneca Ab Chemical compounds
US7348341B2 (en) 2000-05-31 2008-03-25 Astrazeneca Ab Chemical compounds
WO2009010477A1 (fr) * 2007-07-13 2009-01-22 Euroscreen S.A. Noveaux dérivés de piperidine-4-acide acétiques et leur utilisation
US7709500B2 (en) 2002-02-18 2010-05-04 Astrazeneca Ab Chemical compounds
US7956070B2 (en) 2004-02-02 2011-06-07 Astrazeneca Ab Piperidines as chemokine modulators (CCR)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0979818B1 (fr) * 1997-03-21 2003-02-19 Mitsubishi Pharma Corporation Composes d'acide benzoique et leur utilisation medicale
TR200102800T2 (tr) 1999-03-26 2002-01-21 Astrazeneca Ab Yeni bileşikler.

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS52148038A (en) * 1976-06-03 1977-12-08 Beecham Group Ltd Production of novel benzamide and pharmaceutical composition containing same
JPS53139728A (en) * 1977-05-11 1978-12-06 Robins Co Inc A H Composition for enhancing speedto empty stomach of mammals
DE3601731A1 (de) * 1986-01-22 1987-07-23 Merck Patent Gmbh Pyrimidinderivate
JPH01311059A (ja) * 1988-04-19 1989-12-15 Bayer Ag １，３―二置換されたピロリジン
JPH05229942A (ja) * 1992-02-25 1993-09-07 Teikoku Chem Ind Corp Ltd 消化管運動機能改善剤
JPH07242629A (ja) * 1993-12-27 1995-09-19 Tooa Eiyoo Kk 置換環状アミン化合物、その製造法及びそれを含有する循環器官用剤

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS52148038A (en) * 1976-06-03 1977-12-08 Beecham Group Ltd Production of novel benzamide and pharmaceutical composition containing same
JPS53139728A (en) * 1977-05-11 1978-12-06 Robins Co Inc A H Composition for enhancing speedto empty stomach of mammals
DE3601731A1 (de) * 1986-01-22 1987-07-23 Merck Patent Gmbh Pyrimidinderivate
JPH01311059A (ja) * 1988-04-19 1989-12-15 Bayer Ag １，３―二置換されたピロリジン
JPH05229942A (ja) * 1992-02-25 1993-09-07 Teikoku Chem Ind Corp Ltd 消化管運動機能改善剤
JPH07242629A (ja) * 1993-12-27 1995-09-19 Tooa Eiyoo Kk 置換環状アミン化合物、その製造法及びそれを含有する循環器官用剤

Cited By (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6683074B1 (en) 1997-08-18 2004-01-27 Syntex (U.S.A.) Llc Cyclic amine derivatives-CCR-3 receptor antagonists
US6984637B2 (en) 1997-08-18 2006-01-10 Syntex (U.S.A.) Llc Cyclic amine derivatives-CCR-3 receptor antagonists
US6323223B1 (en) 1997-08-18 2001-11-27 Syntex (U.S.A.) Llc Cyclic amine derivatives- CCR-3 receptor antagonists
US6770650B2 (en) 1997-08-18 2004-08-03 Syntex (U.S.A.) Llc Cyclic amine derivatives-CCR-3 receptor antagonists
WO2000031033A1 (fr) * 1998-11-20 2000-06-02 F. Hoffmann-La Roche Ag Antagonistes du recepteur de piperidine ccr-3
ES2158813A1 (es) * 1998-11-20 2001-09-01 Hoffmann La Roche Sales cuaternarias de piperidina antagonistas del receptor ccr-3
US6342509B1 (en) 1998-11-20 2002-01-29 Syntex (U.S.A.) Llc Piperidine quaternary salts- CCR- 3 receptor antagonists
FR2786179A1 (fr) * 1998-11-20 2000-05-26 Hoffmann La Roche Composes quaternaires de piperidine antagonistes du recepteur ccr-3, composition pharmaceutique les contenant, leur utilisation et leur preparation
EP1072596A3 (fr) * 1999-05-28 2001-02-14 Pfizer Inc. Dérivés de 4-arylpipéridine pour le traitement du prurit
US6479516B1 (en) 1999-05-28 2002-11-12 Pfizer Inc 4-arylpiperidine derivatives for the treatment of pruritus
US6903085B1 (en) 1999-08-24 2005-06-07 Astrazeneca, Ab Substituted piperidine compounds useful as modulators of chemokine receptor activity
WO2001014333A1 (fr) * 1999-08-24 2001-03-01 Astrazeneca Uk Limited Composes de piperidine substitues utiles comme modulateurs de l'activite de recepteurs de chimiokine
US7348341B2 (en) 2000-05-31 2008-03-25 Astrazeneca Ab Chemical compounds
US7304077B2 (en) 2000-09-04 2007-12-04 Astrazeneca Ab Chemical compounds
WO2002020484A1 (fr) * 2000-09-04 2002-03-14 Astrazeneca Ab Composes chimiques
US6958350B2 (en) 2001-02-19 2005-10-25 Astrazeneca Ab Chemical compounds
US6960602B2 (en) 2001-03-22 2005-11-01 Astrazeneca Ab Piperidine derivatives as modulators of chemokine receptors
WO2004002948A1 (fr) * 2001-05-16 2004-01-08 Mitsubishi Pharma Corporation Compose amide et utilisation medicinale de ce compose
US7265227B2 (en) 2001-07-23 2007-09-04 Astrazeneca Ab Piperidine derivatives useful as modulators of chemokine receptor activity
US7192973B2 (en) 2001-11-15 2007-03-20 Astrazeneca Ab Piperidine derivatives and their use as modulators of chemokine receptor activity (especially CCR5)
US7709500B2 (en) 2002-02-18 2010-05-04 Astrazeneca Ab Chemical compounds
US7294636B2 (en) 2003-05-09 2007-11-13 Astrazeneca Ab Chemical compounds
US7956070B2 (en) 2004-02-02 2011-06-07 Astrazeneca Ab Piperidines as chemokine modulators (CCR)
WO2009010477A1 (fr) * 2007-07-13 2009-01-22 Euroscreen S.A. Noveaux dérivés de piperidine-4-acide acétiques et leur utilisation

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Publication number Publication date
AU6944596A (en) 1997-04-01
JPH0977742A (ja) 1997-03-25

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