WO2010092287A1 - Derives de n-[(6-aza-bicyclo[3.2.1]oct-1-yl)-aryl-methyl]-benzamide, leur preparation et leur application en therapeutique - Google Patents
Derives de n-[(6-aza-bicyclo[3.2.1]oct-1-yl)-aryl-methyl]-benzamide, leur preparation et leur application en therapeutique Download PDFInfo
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- WO2010092287A1 WO2010092287A1 PCT/FR2010/050204 FR2010050204W WO2010092287A1 WO 2010092287 A1 WO2010092287 A1 WO 2010092287A1 FR 2010050204 W FR2010050204 W FR 2010050204W WO 2010092287 A1 WO2010092287 A1 WO 2010092287A1
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- methyl
- phenyl
- alkyl
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- trifluoromethyl
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- 0 *C(C1(C2)N(CC=C)CC2CCC1)N Chemical compound *C(C1(C2)N(CC=C)CC2CCC1)N 0.000 description 1
- HICVIKNGNTUKIR-UHFFFAOYSA-N C=CCN(CC(C1)CCC2)C12C#N Chemical compound C=CCN(CC(C1)CCC2)C12C#N HICVIKNGNTUKIR-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- 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
- C07D487/08—Bridged systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- 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
- A61K31/403—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 carbocyclic rings, e.g. carbazole
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
Definitions
- the present invention relates to ⁇ / - [(6-aza-bicyclo [3.2.1] oct-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 being optionally substituted with one or more groups chosen independently from one another; other of the fluorine atom, (C 3 -C 7 ) -cycloalkyl, (C 2 -C 4 ) alkenyl, phenyl, (C 6 ) alkoxy, hydroxy; the phenyl group being optionally substituted by one or more 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 ) alkylthio, (C 1 -C 6 ) alkyl-SO 2 , phenyl or heteroaryl, the phenyl group being optionally substituted with 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 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 3 asymmetric carbon atoms. They can therefore exist in the form of diastereoisomers and 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.
- salts are advantageously prepared with pharmaceutically acceptable acids, but the salts of other acids that are useful, for example, for the purification or the isolation of the compounds of formula (I) are also 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 group
- C 1 -C 6 -alkyl represents a carbon chain of 1 to 6 carbon atoms, linear or branched, for example a methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl; alkenyl, a linear or branched, mono- or poly-unsaturated aliphatic group, for example comprising one or two ethylenic unsaturations, amino, an NH 2 alkoxy group, a -O-alkyl group; acetyl, -C (O) -, cyano, -CN, hydroxy, -OH, thioalkyl, alkyl substituted sulfur; halogen atom, fluorine, chlorine, bromine or iodine, haloalkyl, an alkyl group of which one or more hydrogen atoms have been substituted by a halogen.
- 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 consists of the compounds for which R represents a hydrogen atom or a (C 1 -C 6 ) alkyl group; Ri, R2, R ⁇ , R 4 and R 5 being as defined above.
- a second group of compounds is constituted by compounds for which R represents a hydrogen atom or a methyl or ethyl group; Ri, R2, R ⁇ , R 4, Rset R 6 being as defined above.
- a third group of compounds is constituted by compounds for which R 1 represents a phenyl group, optionally substituted by one or more substituents chosen independently of each other among the halogen atoms, the groups (C 1 -
- a fourth group of compounds is constituted by the compounds for which R 1 represents a phenyl group, optionally substituted by one or more substituents chosen independently of one another from halogen atoms, methyl, ethyl, trifluoromethyl, methoxy, hydroxy; Ri, R 2 , R 3, R 4 and Rset R 6 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, halo- (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) alkyl-SO 2 ; R, R 1 , R 3 , R 4 and R 5 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, trifluoromethyl, methyl, methoxy, ethanesulfonyl groups; R, R 1 , R 3 , R 4 and R 5 being as defined above.
- a seventh group of compounds is constituted by the compounds for which:
- R represents a hydrogen atom or a methyl or ethyl group
- - R 1 represents a phenyl group, optionally substituted with one or more substituents chosen independently of one another from halogen atoms, methyl, ethyl, trifluoromethyl, methoxy, hydroxy;
- - R 2 represents one or more substituents chosen from a hydrogen atom, halogen atoms, trifluoromethyl, methyl, methoxy, ethanesulfonyl groups, in the form of a base or of addition salt with an acid.
- the compounds of the invention exhibit particular activity as inhibitors of Glyti glycine transporters, including an improved activity and safety profile.
- a coupling of a diamine of general formula (II) is carried out, in which R and R 1 are as defined above, in particular when R represents an atom of hydrogen, an allyl or phenylmethyl group, with an activated acid, for example via a mixed anhydride or an acid chloride of general formula (III) in which Y represents a leaving group derived for example from benzotriazole, acylurea or a halogen atom and R 2 is as defined above, using the methods known to those skilled in the art.
- R represents a hydrogen atom, or by alkylation with a RX type halide or mesylate, wherein 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 by a reductive amination with a suitable aldehyde or ketone according to the methods known to those skilled in the art, according to the known methods of Skilled person.
- a mineral base for example potassium carbonate in acetonitrile
- 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 the methods illustrated by Schemes 2 for the amine (IIa) and (Nb) and 3 for the amine (IIc) which follow. SCHEME 2
- the nitrile of formula (IVa) is reacted with the lithiated aromatic compound of general formula (V), in which R 1 is as defined above, in an ethereal solvent such as tetrahydrofuran or ether, at low temperature, for example at -70 ° C.
- An imine is thus obtained which is in particular reduced diastereoselectively with a reducing agent such as sodium borohydride, in a protic solvent such as methanol to give the amine of general formula (IIa).
- the amine (IIa) can be debenzylated by hydrogenation in the presence of palladium catalyst to provide the deprotected amine (Nb) (Scheme 2).
- the nitrile of formula (IVc) may also be reacted with the lithiated aromatic compound of general formula (V), in which R 1 is as defined above, in an ethereal solvent such as tetrahydrofuran or the ether, at low temperature for example at -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 (II). ) ( Figure 3).
- the chiral compounds of general formula (I) can be obtained by separation of the racemic compounds by high performance liquid chromatography (HPLC) on a chiral column, or by separation by chromatography on silica gel chiral diastereoisomers of the amine of general formula (IIa) and debenzylation, as described in Scheme 2.
- HPLC high performance liquid chromatography
- nitrile of formula (IVa) is prepared according to a method described in Tetrahedron: Asymmetry, 2006 (17), 252-258 and the nitrile of formula (IVc) is synthesized according to this same reference, using allylamine.
- lithiated aryls of general formula (V) may be prepared according to methods known to those skilled in the art.
- Acids and acid chlorides of general formula (III) are commercially available or prepared by analogy with methods known to those skilled in the art
- the hyphen "-" is part of the word, and the hyphen “_” is only used for the cut at the end of the line; it must be deleted in the absence of a cut, and must not be replaced by a normal dash or a space.
- Example 1 (Compound No. 3): ⁇ - [(6-Azabicyclo [3.2.1] oct-5-yl) phenyl-methyl] - (2,6-dichloro-3-trifluoromethyl) hydrochloride benzamide (1: 1).
- Example 2 (Compound No. 8): (+) - ⁇ / - [(6-aza-bicyclo [3.2.1] oct-5-yl) phenyl-methyl] - (2,6-dichloro-3) hydrochloride trifluoromethyl) benzamide (1: 1).
- the 2 diastereoisomers (IIa) can be separated by separation on silica gel with a mixture of dichloromethane and methanol as eluent.
- the most polar compound is phenyl-C- [6 - ((R) -1-phenyl-ethyl) -6-aza-bicyclo [3.2.1] oct-5-yl] -methylamine (IIa2).
- Example 4 2-Chloro-N - [(6-ethyl-6-aza-bicyclo [3.2.1] oct-5-yl) phenyl-methyl] - (3-trifluoromethyl) benzamide.
- Example 5 2-Chloro-N - [(6-methyl-6-azabicyclo [3.2.1] oct-5-yl) -phenyl-methyl] - (3-trifluoromethyl) hydrochloride ) -benzamide (1: 1).
- Example 6 (Compound No. 23): ⁇ - [(6-Azabicyclo [3.2.1] oct-5-yl) - (3-bromo-phenyl) -methyl] - (2-chloro-3) hydrochloride trifluoromethyl) benzamide (1: 1).
- the compound is obtained according to the method described in Example 1.1, starting from 1 g of 6-allyl-6-aza-bicyclo [3.2.1] octane-5-carbonitrile (IVc), 2.5 equivalents of 3 bromophenyl lithium and 5 equivalents of sodium borohydride. After purification by chromatography on a column of silica gel, eluting with a mixture of dichloromethane and ammoniacal methanol, 260 mg of an oil containing 140 mg of (6-allyl-6-aza-bicyclo [3.2.1] oct-5 are obtained. -yl) - (3-bromo-phenyl) -methylamine (Ile) (0.42 mmol) used as in the next step.
- the mixture is heated for 2 hours at 40 ° C. After cooling, it is diluted with 10 ml of dichloromethane and then hydrolyzed with 5 ml of a sodium carbonate solution. The organic phase is separated and washed twice with 5 ml of hydrochloric acid 1
- the compounds of the table are in the form of hydrochloride solvated with one or more molecules of water,
- Table 2 gives the physical properties, melting points and rotatory powers of the compounds of Table 1.
- column [ ⁇ D ] 2 o ° c gives the result of analysis of the rotatory power of the compounds of the table to the wavelength of 589 nM and at the temperature of
- the compounds of the invention have been subjected to a series of pharmacological tests which have demonstrated their interest as substances with therapeutic activities.
- glycine uptake is studied in SK-N-MC cells (neuronal cells). epithelial 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 effectiveness of the compound is determined by the IC50 concentration of the compound which decreases by 50% the specific uptake of glycine, defined by the difference in radioactivity incorporated by the control group and the batch which received glycine at 10 mM.
- 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 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 forms of administration 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. It can be designed to allow rapid, delayed or sustained release of the active ingredient through polymer matrices or specific polymers used in the coating.
- capsules the active ingredient is mixed with dry pharmaceutical vehicles (simple mixing, dry or wet granulation, or hot melting), liquid or semi-solid.
- dry pharmaceutical vehicles simple mixing, dry or wet granulation, or hot melting
- liquid or semi-solid 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 melting at the rectal temperature, for example cocoa butter or polyethylene glycols, are used.
- 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).
- the topical compositions according to the invention comprise a medium compatible with the skin. They may be in particular in the form of aqueous solutions, alcoholic or aqueous-alcoholic, gels, water-in-oil or oil-in-water emulsions having the appearance of a cream or a 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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Abstract
Description
Claims
Priority Applications (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2010212703A AU2010212703A1 (en) | 2009-02-10 | 2010-02-09 | N-[(6-azabicyclo[3.2.1]oct-1-yl)-aryl-methyl]-benzamide derivatives, preparation thereof, and therapeutic use thereof |
EP10708304A EP2396335A1 (fr) | 2009-02-10 | 2010-02-09 | Derives de n-[(6-aza-bicyclo[3.2.1]oct-1-yl)-aryl-methyl]-benzamide, leur preparation et leur application en therapeutique |
CA2751866A CA2751866A1 (fr) | 2009-02-10 | 2010-02-09 | Derives de n-[(6-aza-bicyclo[3.2.1]oct-1-yl)-aryl-methyl]-benzamide, leur preparation et leur application en therapeutique |
SG2011057213A SG173607A1 (en) | 2009-02-10 | 2010-02-09 | N-[(6-azabicyclo[3.2.1]oct-1-yl)-aryl-methyl]-benzamide derivatives, preparation thereof, and therapeutic use thereof |
JP2011548759A JP2012517412A (ja) | 2009-02-10 | 2010-02-09 | N−[(6−アザビシクロ[3.2.1]オクト−1−イル)−アリール−メチル]−ベンズアミド誘導体、これらの調製およびこれらの治療的使用 |
MX2011008459A MX2011008459A (es) | 2009-02-10 | 2010-02-09 | Derivados de n-[ (6-aza-biciclo [3.2.1] oct-1-il)abril-metil]-benz amida, su preparacion y su aplicacion en terapeutica. |
CN2010800156289A CN102388050A (zh) | 2009-02-10 | 2010-02-09 | N-[(6-氮杂二环[3.2.1]辛-1-基)芳基甲基]苯甲酰胺衍生物、其制备方法以及其治疗用途 |
BRPI1008544A BRPI1008544A2 (pt) | 2009-02-10 | 2010-02-09 | derivados de n-[(6-aza-biciclo [3.2.1] oct-1-il)-aril-metil]-benzamida, o respectivo preparo e a respectiva aplicação em terapêutica |
IL214487A IL214487A0 (en) | 2009-02-10 | 2011-08-07 | N-[(6-azabicyclo[3.2.1]oct-1-yl)-aryl-methyl]-benzamide derivatives, preparation thereof, and therapeutic use thereof |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR0900579A FR2941954B1 (fr) | 2009-02-10 | 2009-02-10 | Derives de n-°(6-aza-bicyclo°3.2.1!oct-1-yl)-aryl-methyl! benzamide, leur preparation et leur application en therapeutique |
FR09/00579 | 2009-02-10 |
Publications (1)
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WO2010092287A1 true WO2010092287A1 (fr) | 2010-08-19 |
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PCT/FR2010/050204 WO2010092287A1 (fr) | 2009-02-10 | 2010-02-09 | Derives de n-[(6-aza-bicyclo[3.2.1]oct-1-yl)-aryl-methyl]-benzamide, leur preparation et leur application en therapeutique |
Country Status (15)
Country | Link |
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EP (1) | EP2396335A1 (fr) |
JP (1) | JP2012517412A (fr) |
KR (1) | KR20110118813A (fr) |
CN (1) | CN102388050A (fr) |
AR (1) | AR075380A1 (fr) |
AU (1) | AU2010212703A1 (fr) |
BR (1) | BRPI1008544A2 (fr) |
CA (1) | CA2751866A1 (fr) |
FR (1) | FR2941954B1 (fr) |
IL (1) | IL214487A0 (fr) |
MX (1) | MX2011008459A (fr) |
SG (1) | SG173607A1 (fr) |
TW (1) | TW201034667A (fr) |
UY (1) | UY32429A (fr) |
WO (1) | WO2010092287A1 (fr) |
Citations (6)
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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 |
FR2861076A1 (fr) * | 2003-10-17 | 2005-04-22 | Sanofi Synthelabo | Derives de n-heterocyclymethylbenzamide, 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 |
WO2008066874A1 (fr) * | 2006-11-30 | 2008-06-05 | Cenerx Biopharma, Inc. | Esters dialkylamino alkylés de la pivagabine utilisés comme médicaments dans le traitement des troubles du système nerveux central |
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 FR0900579A patent/FR2941954B1/fr not_active Expired - Fee Related
-
2010
- 2010-02-09 AU AU2010212703A patent/AU2010212703A1/en not_active Abandoned
- 2010-02-09 JP JP2011548759A patent/JP2012517412A/ja not_active Withdrawn
- 2010-02-09 CA CA2751866A patent/CA2751866A1/fr not_active Abandoned
- 2010-02-09 KR KR1020117021204A patent/KR20110118813A/ko not_active Application Discontinuation
- 2010-02-09 AR ARP100100345A patent/AR075380A1/es unknown
- 2010-02-09 TW TW099104006A patent/TW201034667A/zh unknown
- 2010-02-09 BR BRPI1008544A patent/BRPI1008544A2/pt not_active Application Discontinuation
- 2010-02-09 MX MX2011008459A patent/MX2011008459A/es not_active Application Discontinuation
- 2010-02-09 CN CN2010800156289A patent/CN102388050A/zh active Pending
- 2010-02-09 SG SG2011057213A patent/SG173607A1/en unknown
- 2010-02-09 WO PCT/FR2010/050204 patent/WO2010092287A1/fr active Application Filing
- 2010-02-09 EP EP10708304A patent/EP2396335A1/fr not_active Withdrawn
- 2010-02-10 UY UY0001032429A patent/UY32429A/es not_active Application Discontinuation
-
2011
- 2011-08-07 IL IL214487A patent/IL214487A0/en unknown
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
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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 |
FR2861076A1 (fr) * | 2003-10-17 | 2005-04-22 | Sanofi Synthelabo | Derives de n-heterocyclymethylbenzamide, 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 |
WO2008066874A1 (fr) * | 2006-11-30 | 2008-06-05 | Cenerx Biopharma, Inc. | Esters dialkylamino alkylés de la pivagabine utilisés comme médicaments dans le traitement des troubles du système nerveux central |
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 (1)
Title |
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TETRAHEDRON : ASYMMETRY, 2006, pages 252 - 258 |
Also Published As
Publication number | Publication date |
---|---|
UY32429A (es) | 2010-09-30 |
AR075380A1 (es) | 2011-03-30 |
TW201034667A (en) | 2010-10-01 |
BRPI1008544A2 (pt) | 2016-03-15 |
EP2396335A1 (fr) | 2011-12-21 |
FR2941954B1 (fr) | 2011-04-08 |
FR2941954A1 (fr) | 2010-08-13 |
IL214487A0 (en) | 2011-09-27 |
KR20110118813A (ko) | 2011-11-01 |
CN102388050A (zh) | 2012-03-21 |
AU2010212703A1 (en) | 2011-09-01 |
JP2012517412A (ja) | 2012-08-02 |
SG173607A1 (en) | 2011-09-29 |
CA2751866A1 (fr) | 2010-08-19 |
MX2011008459A (es) | 2011-12-16 |
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