WO2010092286A1 - Derives de n-[(2-aza-bicyclo[2.1.1]hex-1-yl]-aryl-methyl]-benzamide, leur preparation et leur application en therapeutique - Google Patents
Derives de n-[(2-aza-bicyclo[2.1.1]hex-1-yl]-aryl-methyl]-benzamide, leur preparation et leur application en therapeutique Download PDFInfo
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- WO2010092286A1 WO2010092286A1 PCT/FR2010/050203 FR2010050203W WO2010092286A1 WO 2010092286 A1 WO2010092286 A1 WO 2010092286A1 FR 2010050203 W FR2010050203 W FR 2010050203W WO 2010092286 A1 WO2010092286 A1 WO 2010092286A1
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- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/52—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring condensed with a ring other than six-membered
Definitions
- the present invention relates to ⁇ / - [(2-aza-bicyclo [2.2.1] hex-1-yl) -aryl-methyl] -benzamide derivatives, to their preparation and their therapeutic application in the treatment of or the prevention of diseases involving glycine carriers Glyti.
- R represents a hydrogen atom or a group chosen from the (C 6 -C 6 ) alkyl, (C 3 -C 7 ) -cycloalkyl groups, these groups optionally substituted by one or more groups chosen independently from one another; the other of the fluorine atom, (C 3 -C 7 ) -cycloalkyl, (C 2 -C 4 ) alkenyl, phenyl, (C 6 ) alkoxy, hydroxy; the phenyl group is optionally substituted with one or more (d-C 6 ) alkoxy groups;
- R 1 represents a phenyl or naphthyl group, optionally substituted by one or more substituents chosen independently of one another from halogen atoms, (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkoxy groups, halo (CrC 6) alkyl, NR 4 R 5, NR 3 C (O) OR 4, NR 3 SO 2 R 4, NR 3 C (O) R 6, hydroxy, halo (C r C 6) alkoxy, (C 1 -C 6 ) alkyl-thio, (C 1 -C 6 ) alkyl-SO 2 , phenyl or heteroaryl, the phenyl group being optionally substituted by one or more substituents independently selected from halogen atoms, the groups (C 1 -C 6 ) C 6 ) alkyl, (C 1 -C 6 ) alkoxy, halo- (C 1 -C 6 ) alkyl, NR 4 R 5 ,
- R 2 represents one or more substituents chosen from a hydrogen atom, halogen atoms, (C 1 -C 6 ) alkyl, (C 3 -C 7 ) cycloalkyl, (C 3 -C 7 ) - cycloalkyl- (dC 3 ) alkyl, halo- (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkoxy, NR 4 R 5 , phenyl, heteroaryl, cyano, acetyl, (C 1 -C 6 ) thioalkyl, (C 1 -C 6 ) alkylsulfonyl , carboxy or (Ci-C 6) alkoxycarbonyl; the phenyl group being optionally substituted by one or more substituents independently selected from halogen atoms, the groups (Ci-C 6) alkyl, (d- C 6) alkoxy, halo- (C r C6) alkyl
- R 3 , R 4 and R 5 represent, independently of one another, a hydrogen atom or a (C 1 -C 6 ) alkyl group
- R 6 represents a group (dC 6 ) alkyl
- R 4 and R 5 may together form, with the nitrogen atom which bears them, a ring chosen from the azetidine, pyrrolidine, piperidine, morpholine, thiomorpholine, piperazine and azepine rings, optionally substituted by a group (dC 6 ) alkyl; - R 3 and R 4 can form together with the atoms that carry them, a 5- or 6-membered ring;
- R 3 and R 6 can form together with the atoms that carry them, a 5- or 6-membered ring; in the form of a base or an acid addition salt.
- the compounds of formula (I) have an asymmetric carbon atom. They can therefore exist in the form of enantiomers. These enantiomers, including racemic mixtures, form part of the invention.
- the compounds of formula (I) may exist in the form of bases or addition salts with acids. Such addition salts are part of the invention.
- Ct-Cz where t and z can take the values from 1 to 6, a carbon chain which can have from t to z carbon atoms, for example Ci--C 6 carbon chain which can have from 1 to 6 carbon atoms; alkyl, a saturated, linear or branched aliphatic group; for example, a (C 1 -C 6 ) alkyl group represents a linear or branched carbon chain of 1 to 6 carbon atoms, for example methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl or hexyl; alkenyl, an aliphatic mono- or poly-unsaturated group, linear or branched, comprising for example one or two ethylenic unsaturations, alkylene, a saturated divalent alkyl group, linear or branched, for example a Ci -6 alkylene group represents a carbon chain divalent from 1 to 6 carbon atoms
- trifluoromethyl, trifluoroethyl pentafluoroethyl or heteroaryl groups a 5- or 6-membered aromatic monocyclic group comprising from 1 to 3 heteroatoms chosen from nitrogen, oxygen and sulfur.
- a heteroaryl group mention may be made of pyrrole, furan, thiophene, pyrazole, imidazole, triazole, tetrazole, oxazole, isoxazole, oxadiazole, thiazole, isothiazole, thiadiazole, pyridine, pyrimidine, pyrazine, pyridazine and triazine groups.
- a first group of compounds is constituted by compounds for which R represents a hydrogen atom or a (C 1 -C 6 ) alkyl group, optionally substituted with one or a plurality of groups independently selected from fluorine, (C 2 -C 4 ) alkenyl, hydroxy, (C 3 -C 7 ) -cycloalkyl or phenyl; R 1, R 2 , R 3 , R 4 , R 5 and R 6 being as defined above.
- a second group of compounds is constituted by compounds for which R represents a hydrogen atom or a methyl, ethyl, propyl, / sobutyl or allyl group.
- the methyl, ethyl, and / or sobutyl groups being optionally substituted by one or more groups chosen independently of one another from the fluorine atom, the hydroxy group, a cyclopropyl or phenyl group; R 1, R 2, R B, R 4 , R 5 and R 6 being as defined above.
- a third group of compounds is constituted by the compounds for which R 1 represents a phenyl or naphthyl group, optionally substituted by one or more halogen atoms or groups (C 1 -C 4).
- R 1 represents a phenyl or naphthyl group, optionally substituted by one or more halogen atoms or groups (C 1 -C 4).
- R, R 2 , R 3, R 4 , and R 5 being as defined above.
- a fourth group of compounds is constituted by the compounds for which R 1 represents a phenyl or naphthyl group, optionally substituted by one or more halogen atoms or methyl or methoxy groups. trifluoromethyl, NH 2 or hydroxy; R, R 2 R 4 and R 5 being as defined above.
- a fifth group of compounds is constituted by the compounds for which R 2 represents one or more substituents chosen from hydrogen, halogen atoms, NR 4 R 5 , (C 1 -C 6 ) alkoxy, halo- (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkylthio, (C 1 -C 6 ) alkyl-SO 2 ; R, R 1 , R 3 , R 4 , R 5 and R 6 being as defined above.
- a sixth group of compounds is constituted by the compounds for which R 2 represents one or more substituents chosen from hydrogen, halogen atoms, methyl, ethyl, NH 2 , methoxy, trifluoromethyl, methanesulfanyl, ethanesulfonyl,
- a seventh group of compounds is constituted by the compounds for which:
- - R represents a hydrogen atom or a methyl, ethyl, propyl, / sobutyl, allyl group, the methyl, ethyl, / sobutyl group being optionally substituted by one or more groups chosen independently of one another from the fluorine atom, the hydroxy, cyclopropyl or phenyl groups;
- R 1 represents a phenyl or naphthyl group, optionally substituted by one or more halogen atoms or methyl, methoxy, trifluoromethyl, NH 2 or hydroxyl groups;
- - R 2 represents one or more substituents chosen from hydrogen, halogen atoms, methyl, ethyl, NH 2 , methoxy, trifluoromethyl, methanesulfanyl, ethanesulfonyl, and their addition salts with an acid.
- the compounds of the invention exhibit particular activity as inhibitors of Glyti glycine transporters, including an improved activity and safety profile.
- the compounds of general formula (I) in which R is different from the hydrogen atom can also be prepared from compounds of general formula (I) in which R represents a hydrogen atom, or by alkylation of said compound of general formula (I) with an RX type halide or mesylate, in which R is as defined above and X is mesylate or halogen, in the presence of a mineral base, for example potassium carbonate in acetonitrile ; either by an Eschweiler-Clarke type reaction or a reductive amination with an appropriate aldehyde or ketone according to the methods known to those skilled in the art; or with an appropriate epoxy derivative, according to the methods known to those skilled in the art.
- the compounds of general formula (I) in which the group R 1 is a phenyl group substituted by a hydroxyl may be obtained from the corresponding compound of general formula (I) substituted by a methoxy, using the methods known to man of the job.
- the diamine of general formula (II) can be prepared by processes illustrated by Schemes 2 for the amine (IIa) and 3 for the amine (Nb) and (IIc) which follow:
- the ester (IV) is converted to the amide (V) by heating the trimethylaluminum complex and the appropriate amine, such as morpholine, under the reflux of a solvent such as toluene.
- the amine (V) may be deprotected to obtain the compound (VI) using a phenyllithium-type lithian in a solvent such as tetrahydrofuran at low temperature, for example at -70 ° C. It is then proceeded to a ⁇ / allyl bromide-allyl in the presence of a base such as potassium carbonate, in a solvent such as acetonitrile at room temperature, to obtain the compound (VII).
- the morpholinic amide of formula (VII) is reacted with the lithiated aromatic compound of general formula (VIII), in which R 1 is as defined above, in an ethereal solvent such as ether or tetrahydrofuran, at low temperature. temperature.
- a ketone of general formula (IX) is thus obtained which is reacted with O-benzylhydroxylamine hydrochloride, under reflux of pyridine, to obtain a mixture of oxime Z / E of general formula (X).
- the oxime (X) is then reduced at reflux of the ether by the lithium aluminum hydride double, to provide the diamine of general formula (IIa).
- a nitrile of formula (XI) is reacted with the lithiated aromatic compound of general formula (VIII), in which R 1 is as defined above, in an ethereal solvent such as tetrahydrofuran or ether, at low temperature, for example -70 ° C.
- An imine is thus obtained which is reduced with a reducing agent such as sodium borohydride in a protic solvent such as methanol, to give the amine of general formula (Nb) .
- the amine (Nb) can be debenzylated by hydrogenation in the presence of palladium catalyst to provide the deprotected amine (Ile).
- the chiral compounds of general formula (I) corresponding to the S or R enantiomers can be obtained by separation of the racemic compounds by high performance liquid chromatography (HPLC) on a chiral column, or could be obtained by resolution of the racemic amine of general formula (II) using a chiral acid, such as dibenzoyl-tartaric acid or by fractional and preferential recrystallization of a diastereoisomeric salt.
- HPLC high performance liquid chromatography
- ester of formula (IV) is prepared according to a method described in J. Org. Chem.
- nitrile of formula (XI) is prepared according to a method described in Tetrahedron: Asymmetry, 2006 (17), 252-258.
- Acids and acid chlorides of general formula (III) are commercially available or prepared by analogy with methods known to those skilled in the art.
- m means multiplet, "s” singlet, “t” triplet, “d” doublet, "q” quadruplet, dxd means double doublet, txt means triple triplet, dxt double triplet, and so on.
- Example 1 (Compound No. 9): ⁇ - [(2-Azabicyclo [2.1.1] hex-1-yl) -phenylmethyl] - (2-chloro-5-trifluoromethyl) benzamide hydrochloride (1 : 1).
- reaction medium is then diluted with 10 ml of dichloromethane and then washed successively with water (5 ml), 1N sodium hydroxide (5 ml) and in a saturated solution of sodium chloride (5 ml).
- the organic phase is dried over sodium sulfate, filtered and evaporated under reduced pressure.
- the residue is purified by chromatography on a column of silica gel, eluting with a mixture of dichloromethane and ammoniacal methanol. 0.24 g of ⁇ - [(2-allyl-2-aza-bicyclo [2.1.1] hex-1-yl) -phenyl-methyl] - (2-chloro-5-trifluoromethyl) -benzamide are thus obtained. (la) as an oil.
- the organic phase is separated and washed twice with 5 ml of 1N hydrochloric acid.
- the aqueous phases are combined and then basified with aqueous ammonia at pH 9 and then extracted twice with 25 ml of dichloromethane.
- the organic phases are dried over sodium sulphate, filtered and evaporated under reduced pressure.
- 0.1 g of ⁇ - [(2-aza-bicyclo [2.1.1] hex-1-yl) -phenyl-methyl] - (2-chloro-5-trifluoromethyl) -benzamide are thus obtained, which is salified under form of hydrochloride by solubilization of the base in ether and then adding an excess of 1 N hydrochloric acid in ether.
- the solid obtained is filtered and then dried under vacuum.
- Example 2 (Compound No. 5): N - [(2-Azabicyclo [2.1.1] hex-1-yl) -phenylmethyl] - (2-chloro-3-trifluoromethyl) -benzamide Hydrochloride ( 1: 1).
- the residue is taken up in 100 ml of ether and 100 ml of water.
- the medium is acidified with a 1N hydrochloric acid solution, and then the ether phase is extracted.
- aqueous phase is basified with ammonia and then reextracted twice with 100 ml of dichloromethane.
- the organic phases are combined, then dried over sodium sulphate, filtered and evaporated under reduced pressure. 4.15 g of (2-benzyl-2-aza-bicyclo [2.1.1] hex-1-yl) -phenyl-methylamine (Nb) are thus obtained in the form of an oil which crystallizes in the cold.
- An analytical sample is obtained in hydrochloride form by solubilization of the base in ether, addition of an excess of 1N hydrochloric acid in ether, and concentration under reduced pressure.
- Example 5 (2,6-Dichloro) -N- (phenyl- [2- (2,2,2-trifluoro-ethyl) -2-azabicyclo [2.1.1] hex) 1-yl] methyl ⁇ - (3-trifluoromethyl) -benzamide.
- Example 6 2-Chloro-N - [(2-methyl-2-azabicyclo [2.1.1] hex-1-yl) -phenyl-methyl] - (3-trifluoromethyl) hydrochloride ) -benzamide (1: 1).
- the compounds of the table are in the form of hydrochloride solvated with one or more molecules of water, the compounds n ° 13 and 14 of the table form a pair of enantiomers which are separated by preparative HPLC, by using a CHIRALpak ® AD 20 ⁇ m column and as solvent a 95/5 isohexane / propan-2-ol mixture.
- Table 2 gives the physical properties, melting points and rotational potency of the compounds of Table 1.
- Table 2 :
- the column [ ⁇ D ] 2 o ° c gives the result of analysis of the rotatory power of the compounds of the table at the wavelength of 589 nM and at a temperature of 20 ° C.
- the solvent indicated in parentheses corresponds to the solvent used to measure the rotational power in degrees and the letter “c” indicates the concentration of the solvent in g / 100 ml, "NA” means that the measurement of the rotatory power is not applicable,
- the "LCMS MH + " column gives information on the molecular ion (M + H +) or (M +) observed by mass spectrometry analysis of the products, or by LC-MS (liquid chromatography coupled to Mass Spectroscopy) carried out on an apparatus of Agilent LC-MSD Trap in ESI positive mode, either by direct MS (Mass Spectroscopy) on an Autospec M (EBE) device using the DCI-NH 3 technique or by using the electronic impact technique on a type Waters GCT.
- the compounds of the invention have been subjected to a series of pharmacological tests which have demonstrated their interest as substances with therapeutic activities. Study of the glycine transport in SK-N-MC cells expressing the native glyti human transporter.
- glycine uptake is studied in SK-N-MC cells (human neuroepithelial cells) expressing the native human glyti transporter by measuring the radioactivity incorporated in the presence or absence of the test compound.
- the cells are cultured in monolayer for 48 h in 0.02% fibronectin pretreated plates. On the day of the experiment, the culture medium is removed and the cells are washed with Krebs-HEPES buffer ([4- (2-hydroxyethyl) piperazine-1-ethanesulfonic acid) at pH 7.4. After 10 minutes of preincubation at 37 ° C.
- Krebs-HEPES buffer [4- (2-hydroxyethyl) piperazine-1-ethanesulfonic acid
- the compounds of the invention in this test, have an Cl 50 of the order of 0.001 to 10 ⁇ M.
- Table 3 shows some examples of Cl 50 results for compounds according to the invention.
- the compounds of the invention can be used for the treatment of cognitive and / or behavioral disorders associated with neurodegenerative diseases, dementia; for the treatment of psychoses, in particular schizophrenia (deficient form and productive form), acute or chronic extrapyramidal symptoms induced by neuroleptics; for the treatment of various forms of anxiety, panic attacks, phobias, obsessive-compulsive disorders; for the treatment of various forms of depression, including psychotic depression; for the treatment of bipolar disorders, manic disorders, mood disorders; for the treatment of disorders due to alcohol abuse or withdrawal, sexual behavior disorders, eating disorders, migraine; pain ; sleep disorders.
- the compounds according to the invention can therefore be used for the preparation of medicaments, in particular inhibitory inhibitory drugs of the glycine glycine transporter.
- the invention relates to medicaments which comprise a compound of formula (I), or an addition salt thereof to a pharmaceutically acceptable acid or a hydrate or a solvate of the compound of formula (I).
- the present invention also relates to pharmaceutical compositions containing an effective dose of at least one compound according to the invention, in the form of a base or a pharmaceutically acceptable salt or solvate, and in a mixture, where appropriate, with suitable excipients.
- Said excipients are chosen according to the pharmaceutical form and the desired mode of administration.
- compositions according to the invention can thus be intended for oral, sublingual, subcutaneous, intramuscular, intravenous, topical, intratracheal, intranasal, transdermal, rectal, intraocular administration.
- the unit dosage forms may be, for example, tablets, capsules, granules, powders, oral or injectable solutions or suspensions, transdermal patches, suppositories.
- topical administration we can consider ointments, lotions and eye drops.
- Said unit forms are dosed to allow a daily administration of 0.01 to 20 mg of active ingredient per kg of body weight, according to the dosage form.
- a pharmaceutical carrier which may be composed of diluents, for example lactose, microcrystalline cellulose or starch, and formulation adjuvants such as binders, polyvinylpyrrolidone, is added to the active ingredient, which may or may not be micronized. hydroxy-propylmethylcellulose, etc.), flow agents such as silica, lubricants such as magnesium stearate, stearic acid, glycerol tribehenate, sodium stearyl fumarate. Wetting agents or surfactants such as sodium lauryl sulphate may also be added.
- the production techniques can be direct compression, dry granulation, wet granulation or hot melt.
- the tablets may be bare, sugar-coated, for example with sucrose, or coated with various polymers or other suitable materials. They can be designed to allow rapid, delayed or prolonged release of the active ingredient through polymer matrices or specific polymers used in the coating.
- the active ingredient is mixed with dry pharmaceutical vehicles (simple mixing, dry or wet granulation, or hot melting), liquid or semi-solid.
- the capsules may be hard or soft, film-coated or not, so as to have a rapid, prolonged or delayed activity (for example for an enteric form).
- a composition in the form of syrup or elixir or for administration in the form of drops may contain the active ingredient together with a sweetener, preferably acaloric, methylparaben or propylparaben as antiseptic, a flavoring agent and a dye.
- a sweetener preferably acaloric, methylparaben or propylparaben as antiseptic, a flavoring agent and a dye.
- Water-dispersible powders and granules may contain the active ingredient in admixture with dispersing agents or wetting agents, or dispersing agents such as polyvinylpyrrolidone, as well as with sweeteners and taste-correcting agents.
- dispersing agents or wetting agents or dispersing agents such as polyvinylpyrrolidone
- sweeteners and taste-correcting agents for rectal administration, suppositories prepared with binders are used melting at the rectal temperature, for example cocoa butter or polyethylene glycols.
- aqueous suspensions For parenteral administration, aqueous suspensions, isotonic saline solutions or sterile injectable solutions containing pharmacologically compatible dispersing agents and / or wetting agents, for example propylene glycol or butylene glycol, are used.
- pharmacologically compatible dispersing agents and / or wetting agents for example propylene glycol or butylene glycol
- the active ingredient may also be formulated in the form of microcapsules, optionally with one or more supports or additives, or with a polymer matrix or with a cyclodextrin (transdermal patches, sustained-release forms).
- compositions according to the invention comprise a medium compatible with the skin. They may be in the form of aqueous, alcoholic or aqueous-alcoholic solutions, gels, water-in-oil or oil-in-water emulsions having the appearance of a cream or gel, microemulsions, aerosols, or in the form of vesicular dispersions containing ionic and / or nonionic lipids. These galenic forms are prepared according to the usual methods of the fields considered.
- a unitary form of administration of a compound according to the invention in tablet form may comprise the following components:
- the dose of active ingredient administered per day can reach 0.1 to 20 mg / kg, in one or more doses.
- the dosage appropriate to each patient is determined by the physician according to the mode of administration, the weight and the response of said patient.
- the present invention also relates to a method of treatment of the pathologies indicated above which comprises the administration to a patient of an effective dose of a compound according to the invention, or one of pharmaceutically acceptable salts thereof.
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Priority Applications (11)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SG2011057205A SG173606A1 (en) | 2009-02-10 | 2010-02-09 | N-[(2-azabicyclo[2.1.1]hex-1-yl]-aryl-methyl]-benzamide derivatives, preparation thereof, and therapeutic use thereof |
MX2011008447A MX2011008447A (es) | 2009-02-10 | 2010-02-09 | Derivados de n-[(2-aza-biciclo[2.1.1]hex-1-il)-abril-metil]-benzam ida, su prepracion y su uso en terapeutica. |
RU2011137463/04A RU2011137463A (ru) | 2009-02-10 | 2010-02-09 | Производные n-[([2.1.1]гекс-1-ил)арилметил] бензамида, их получение и применение в терапии |
CN2010800150193A CN102388049A (zh) | 2009-02-10 | 2010-02-09 | N-[(2-氮杂双环[2.1.1]己-1-基)-芳基-甲基]-苯甲酰胺衍生物、其制备及其治疗用途 |
BRPI1008660A BRPI1008660A2 (pt) | 2009-02-10 | 2010-02-09 | derivados de n-[(2-aza-biciclo[2.1.1] hex-1-il)-aril-metil]benzamida, sua preparação e sua aplicação em teraêutica |
US13/148,583 US20120071536A1 (en) | 2009-02-10 | 2010-02-09 | N-[(2-azabicyclo[2.1.1]hex-1-yl)-aryl-methyl]-benzamide derivatives, preparation thereof, and therapeutic use thereof |
CA2751863A CA2751863A1 (fr) | 2009-02-10 | 2010-02-09 | Derives de n-[(2-aza-bicyclo[2.1.1]hex-1-yl]-aryl-methyl]-benzamide, leur preparation et leur application en therapeutique |
JP2011548758A JP2012517411A (ja) | 2009-02-10 | 2010-02-09 | N−[(2−アザビシクロ[2.1.1]ヘキス−1−イル)−アリール−メチル]−ベンズアミド誘導体類、これらの製造およびこれらの治療使用 |
AU2010212702A AU2010212702A1 (en) | 2009-02-10 | 2010-02-09 | N-[(2-azabicyclo[2.1.1]hex-1-yl]-aryl-methyl]-benzamide derivatives, preparation thereof, and therapeutic use thereof |
EP10708303A EP2396334A1 (fr) | 2009-02-10 | 2010-02-09 | Derives de n-[(2-aza-bicyclo[2.1.1]hex-1-yl]-aryl-methyl]-benzamide, leur preparation et leur application en therapeutique |
IL214490A IL214490A0 (en) | 2009-02-10 | 2011-08-07 | N-[(2-azabicyclo[2.1.1]hex-1-yl)-aryl-methyl]-benzamide derivatives, preparation thereof, and therapeutic use thereof |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR0900578 | 2009-02-10 | ||
FR0900578A FR2941953B1 (fr) | 2009-02-10 | 2009-02-10 | Derives de n-°(2-aza-bicyclo°2.1.1!hex-1-yl)-benzamide, leur preparation et leur application en therapeutique |
Publications (1)
Publication Number | Publication Date |
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WO2010092286A1 true WO2010092286A1 (fr) | 2010-08-19 |
Family
ID=40935627
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/FR2010/050203 WO2010092286A1 (fr) | 2009-02-10 | 2010-02-09 | Derives de n-[(2-aza-bicyclo[2.1.1]hex-1-yl]-aryl-methyl]-benzamide, leur preparation et leur application en therapeutique |
Country Status (17)
Country | Link |
---|---|
US (1) | US20120071536A1 (fr) |
EP (1) | EP2396334A1 (fr) |
JP (1) | JP2012517411A (fr) |
KR (1) | KR20110118812A (fr) |
CN (1) | CN102388049A (fr) |
AR (1) | AR075379A1 (fr) |
AU (1) | AU2010212702A1 (fr) |
BR (1) | BRPI1008660A2 (fr) |
CA (1) | CA2751863A1 (fr) |
FR (1) | FR2941953B1 (fr) |
IL (1) | IL214490A0 (fr) |
MX (1) | MX2011008447A (fr) |
RU (1) | RU2011137463A (fr) |
SG (1) | SG173606A1 (fr) |
TW (1) | TW201036979A (fr) |
UY (1) | UY32428A (fr) |
WO (1) | WO2010092286A1 (fr) |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2861076A1 (fr) * | 2003-10-17 | 2005-04-22 | Sanofi Synthelabo | Derives de n-heterocyclymethylbenzamide, leur preparation et leur application en therapeutique |
FR2861070A1 (fr) * | 2003-10-17 | 2005-04-22 | Sanofi Synthelabo | Derives de n-[phenyl(pyrrolidin-2-yl)methyl]benzamide et n-[(azepan-2-yl)phenylmethyl]benzamide, leur preparation et leur application en therapeutique |
WO2005058317A1 (fr) * | 2003-12-18 | 2005-06-30 | Glaxo Group Limited | Inhibiteurs du transporteur-1 de la glycine |
WO2007053400A2 (fr) * | 2005-10-28 | 2007-05-10 | Merck & Co., Inc. | Inhibiteurs de transporteurs de glycine de type pipéridine |
WO2009013535A1 (fr) * | 2007-07-23 | 2009-01-29 | Astrazeneca Ab | Dérivés de 2-azabicyclo(2,2,2)octane en tant que modulateurs du récepteur transporteur de type i de la glycine |
-
2009
- 2009-02-10 FR FR0900578A patent/FR2941953B1/fr not_active Expired - Fee Related
-
2010
- 2010-02-09 MX MX2011008447A patent/MX2011008447A/es not_active Application Discontinuation
- 2010-02-09 KR KR1020117021203A patent/KR20110118812A/ko not_active Application Discontinuation
- 2010-02-09 SG SG2011057205A patent/SG173606A1/en unknown
- 2010-02-09 RU RU2011137463/04A patent/RU2011137463A/ru unknown
- 2010-02-09 CA CA2751863A patent/CA2751863A1/fr not_active Abandoned
- 2010-02-09 AU AU2010212702A patent/AU2010212702A1/en not_active Abandoned
- 2010-02-09 TW TW099104005A patent/TW201036979A/zh unknown
- 2010-02-09 US US13/148,583 patent/US20120071536A1/en not_active Abandoned
- 2010-02-09 CN CN2010800150193A patent/CN102388049A/zh active Pending
- 2010-02-09 EP EP10708303A patent/EP2396334A1/fr not_active Withdrawn
- 2010-02-09 AR ARP100100344A patent/AR075379A1/es unknown
- 2010-02-09 BR BRPI1008660A patent/BRPI1008660A2/pt not_active Application Discontinuation
- 2010-02-09 WO PCT/FR2010/050203 patent/WO2010092286A1/fr active Application Filing
- 2010-02-09 JP JP2011548758A patent/JP2012517411A/ja not_active Withdrawn
- 2010-02-10 UY UY0001032428A patent/UY32428A/es not_active Application Discontinuation
-
2011
- 2011-08-07 IL IL214490A patent/IL214490A0/en unknown
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2861076A1 (fr) * | 2003-10-17 | 2005-04-22 | Sanofi Synthelabo | Derives de n-heterocyclymethylbenzamide, leur preparation et leur application en therapeutique |
FR2861070A1 (fr) * | 2003-10-17 | 2005-04-22 | Sanofi Synthelabo | Derives de n-[phenyl(pyrrolidin-2-yl)methyl]benzamide et n-[(azepan-2-yl)phenylmethyl]benzamide, leur preparation et leur application en therapeutique |
WO2005058317A1 (fr) * | 2003-12-18 | 2005-06-30 | Glaxo Group Limited | Inhibiteurs du transporteur-1 de la glycine |
WO2007053400A2 (fr) * | 2005-10-28 | 2007-05-10 | Merck & Co., Inc. | Inhibiteurs de transporteurs de glycine de type pipéridine |
WO2009013535A1 (fr) * | 2007-07-23 | 2009-01-29 | Astrazeneca Ab | Dérivés de 2-azabicyclo(2,2,2)octane en tant que modulateurs du récepteur transporteur de type i de la glycine |
Non-Patent Citations (2)
Title |
---|
J. ORG. CHEM., 10320, pages 9348 - 9355 |
TETRAHEDRON : ASYMMETRY, 10620, pages 252 - 258 |
Also Published As
Publication number | Publication date |
---|---|
CA2751863A1 (fr) | 2010-08-19 |
US20120071536A1 (en) | 2012-03-22 |
UY32428A (es) | 2010-09-30 |
TW201036979A (en) | 2010-10-16 |
AR075379A1 (es) | 2011-03-30 |
CN102388049A (zh) | 2012-03-21 |
RU2011137463A (ru) | 2013-03-20 |
BRPI1008660A2 (pt) | 2016-03-08 |
SG173606A1 (en) | 2011-09-29 |
JP2012517411A (ja) | 2012-08-02 |
FR2941953B1 (fr) | 2011-04-08 |
IL214490A0 (en) | 2011-09-27 |
FR2941953A1 (fr) | 2010-08-13 |
EP2396334A1 (fr) | 2011-12-21 |
AU2010212702A1 (en) | 2011-09-01 |
MX2011008447A (es) | 2011-11-29 |
KR20110118812A (ko) | 2011-11-01 |
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