MXPA06009396A - Derivatives of heteroaryl-alkylcarbamates, preparation method thereof and use of same as faah enzyme inhibitors - Google Patents

Abstract

The invention relates to a compound having general formula (I), wherein:A is selected from among one or more X, Y and/or Z groups;X represents an optionally-substituted methylene group;Y represents a C2-alkenylene, optionally substituted, or a C2-alkynylene;Z represents a C3-7 cycloalkyl group;n represents an integer varying between 1 and 7;R1 represents an optionally-substituted heteroaryl or naphthalenyl type group;and R7 represents a hydrogen atom or a C1-6 alkyl group;R8 represents a hydrogen atom or a C1-6 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl-C1-3 alkylene group. The inventive compound takes the form of a base, an acid addition salt, a hydrate or a solvate. Said compounds have an inhibitory activity on the FAAH enzyme.

Description

DERIVATIVES OF HETEROARIL-ALQUILCARBA ATOS, ITS PREPARATION AND ITS APPLICATION AS INHIBITORS OF THE ENZIMA FAAH The invention relates to the derivatives of aryl and heteroaryl alkylcarbamates, their preparation and their application in therapy. There are known derivatives of phenylalkylcarbamates and dioxan-2-alkylcarbamates, described respectively in documents FR2850377 A and WO2004 / 020430 A2, inhibitors of the enzyme FAAH (Fatty Acid Amido Hydrolase). There is still a need to find and develop products inhibiting the FAAH enzyme. The compounds of the invention respond to this objective. The compounds of the invention correspond to the general formula (I): (l) wherein A is selected from one or more groups X, Y and / or Z; X represents a methylene group optionally substituted with one or two C1-C6 alkyl, C3-7 cycloalkyl or C3-7 cycloalkyl-C- | 3 alkykylene; And it represents well a substituted alkenylene-C2 group optionally with one or two C1-C6 alkyl, C3-7 cycloalkyl or C3-7 cycloalkyl-C-3 alkylene groups; either an alkynylene-C2 group; Z represents a group of formula: m represents an integer ranging from 1 to 5; p and q represent integers and are defined so that p + q is a number that goes from 1 to 5; n represents an integer ranging from 1 to 7; R? represents a group R2 optionally substituted with one or more groups R3 and / or R4; R 2 represents a group selected from pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, pyrrolyl, furanyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, naphthalenyl, quinolinyl, tetrahydroquinolinyl, isoquinolinyl, tetrahydroisoquinolinyl, 2-oxo-3,4-dihydroquinolinyl, 1 -oxo-3,4-dihydroisoquinolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, cinolinyl, naphthyridinyl, benzofuranyl, dihydrobenzofuranyl, benzothienyl, dihydrobenzothienyl, indolyl, indolinyl, indazolyl, isoindolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzoxadiazolyl, benzothiadiazolyl, pyrrolopyridinyl, furopyridinyl, thienopyridinyl, imidazopyridinyl, oxazolopyridinyl, thiazolopyridinyl, pyrazolopyridinyl, isoxazolopyridinyl or isothiazolopyridinyl; R3 represents a group chosen from halogen atoms, cyano, nitro, C1-C6 alkyl, C3-7 cycloalkyl, C1-6 alkoxy, hydroxyl, C1-6 thioalkyl, C1 -6 fluoroalkyl, C1-fluoroalkoxy groups -6, fluorothioalkyl-C1 -6, NR5R6, NR5COR6, NR5CO2R6, NR5SO2R6, COR5, CO2R5, CONR5R6, SO2R5, SO2NR5R6, -O- (alkylene-C1-3) -O and phenyl, the phenyl group being optionally substituted with one or several halogen atoms; R represents a group selected from the group phenyl, phenyloxy, benzyloxy, naphthalenyl, pyridinyl, pyrimidinyl, pyridazinyl or pyrazinyl; the R4 group (s) having one or more R3 groups identical or different from one another may be substituted; R5 and Re independently represent a hydrogen atom or a C6-C6 alkyl group, or form with the atom (s) that contain them a cycle selected from a cyclo azetidine, pyrrolidine, piperidine, morpholine, thiomorpholine group , azepine or piperazine, this cycle being optionally substituted with a C-6-alkyl or benzyl group; R7 represents a hydrogen atom or an alkyl-C-? -6 group; R8 represents a hydrogen atom or a C1-C6 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl-C1-3 alkylene group. In the context of the invention, the compounds of general formula (I) can therefore comprise several A groups identical or different from each other. Among the compounds of general formula (I), a first subgroup of compounds consists of compounds for which: A is chosen from one or more groups X and / or Y; X represents a methylene group; Y represents a C2-alkynylene group; n represents an integer ranging from 1 to 5; R- \ represents a group R2 optionally substituted with one or more groups R3 and / or R4; R 2 represents a group chosen from pyridinyl, pyrimidinyl, pyridazinyl, imidazolyl, oxazolyl, pyrazolyl, isoxazolyl, oxadiazolyl, naphthalenyl, quinolinyl, isoquinolinyl, dihydroisoquinolinyl, 2-oxo-3,4-dihydroquinolinyl, indolyl, benzimidazolyl or pyrrolopyridinyl; R3 represents a group selected from halogen atoms, more particularly chlorine and fluorine atoms, C1-C6 alkyl groups, more particularly methyl, C3-7 cycloalkyl, more particularly cyclopropyl, C1-6 alkoxy, more particularly methoxy, NR5R6 and phenyl; R4 represents a group chosen from the phenyl, naphthalenyl or pyridinyl groups; the R group (s) having one or more R3 groups identical or different from one another may be substituted; R5 and R6 independently represent one C1-C6 alkyl group, more particularly methyl; R7 represents a hydrogen atom or a C1-C6 alkyl group; R8 represents a hydrogen atom or a C-C6-alkyl, C3-7 cycloalkyl or C3-7 cycloalkyl-C3-alkylene group. Among the compounds of general formula (I), a second subgroup of compounds consists of compounds for which: A, X, Y, Z, m, p, q, n, R1; R3, R4, R5, R6, R7 and Rs are as defined in general formula (I) or in the first subgroup such as defined above, and R2 represents a group selected from pyridinyl, pyrimidinyl, oxazolyl, isoxazolyl, naphthalenyl, quinolinyl or isoquinolinyl. Among the compounds of general formula (I), a third subgroup of compounds consists of compounds for which: A, X, Y, Z, m, p, q, n, R,, R2, R3, R4, R5 and R6 are as defined in general formula (I) or in subgroups such as defined above; R7 represents a hydrogen atom; R8 represents a hydrogen atom or a C1-6 alkyl group, more particularly methyl. Among the compounds of the subgroups defined above, the following compounds may be mentioned: - [(5-phenylpyridin-2-yl) methyl] carbamic acid 2- (methylamino) -2-oxoethyl-2- (5-phenylpyridin-2- 2- (Methylamino) -2-oxoethyl-2- (6-phenylpyridin-3-yl) ethylcarbamate 2- (methylamino) -2-oxoethyl-2- (2-phenylpyrimidin-5-yl) ethylcarbamate ethyl ester) 2- (Methylamino) -2-oxoethyl 2- (methylamino) -2-oxoethyl 2- (5-phenylpyrimidin-2-yl) ethylcarbamate 2- (4-chlorophenyl) -pyrimidin 2- (methylamino) -2-oxoethyl-4-yl] ethylcarbamate -2- [6- (4-chlorophenyl) -2-methyl-pyrimidin-4-yl] ethylcarbamate from 2- (Methylamino) -2-oxoethyl -2- [6- (4-chlorophenyl) -2- (dimethylamino) -pyrimidin-4-yl-ethylcarbamate 2- (methylamino) -2-oxoethyl- (2-isoquinolin-7-) 2- (methylamino) -2-oxoethyl 2- (2-phenyl-1,3-oxazol-4-yl) ethylcarbamate 2- (methylamino) -2-oxoethyl carbamate 2- [5- (4 2- (Methylamino) -2-oxoethyl- (3-pyridin-2-ylpropyl) -carbamic acid 2-amino-2-oxoethyl- (3-pyridin-3-ylpropyl) -isoxazol-3-yl] ethylcarbamate 2-amino-2-oxoethyl- (3-pyridin-4-ylpropyl) carbamate 2-amino-2-oxoethyl- (3-pyrimidin-5-ylpropyl) carbamate 2-amino-2-oxoethyl carbamate -3- [6- (4-chlorophenyl) -pyrimidin-4-yl] propylcarbamate 2- (methylamino) -2-oxoethyl -3- [6- (4-chlorophenyl) -2-methyl-pyrimidin-4-yl] propylcarbamate 2- (Methylamino) -2-oxoethyl- (3-quinoline-) 2- (methylamino) -2-oxoethyl -3- [6- (4-chlorophenyl) -2- (dimethylamino) -pyrimidin-4-yl] propylcarbamate 2-amino-2-oxoethyl 2-ylpropyl) carbamate - 2-aminomethyl 2-amino-2-oxoethyl - (3-quinolin-4-ylpropyl) carbamate - (3-isoquinolin-1-ylpropyl) carbamate 2- (2-Amino-2-oxoethyl) -3- [5- (4-chlorophenyl) -isoxazol-3-yl] propylcarbamate 2- (3-isoquinolin-4-ylpropyl) carbamate 2-Amino-2-oxoethyl-3- [3- (4-chlorophenyl) -isoxazole-5- (3- (4-chlorophenyl) -isoxazol-5-yl] propylcarbamate (methylamino) -2-oxoethyl-3 - [3- (4-chlorophenyl) -isoxazol-5-yl] propylcarbamate 2- (Methylamino) -2-oxoethyl-3- [3- (4-phenyl-phenyl) -isoxazol-5-yl) propylcarbamate 2- (methylamino) -2-oxoethyl-3- [3-yl] propylcarbamate 2- (Methylamino) -2-oxoethyl- (4-pyridin-2-ylbutyl) carbamic acid (2-amino-2-oxoethyl) -naphthalene-2-oxoethyl (naphthalen-2-yl) -isoxazol-5-yl] propylcarbamate (4-pyridin- 3-amino-2-oxoethyl-3-ylbutyl) carbamic acid 2-amino-2-oxoethyl- (4-pyridin-4-ylbutyl) carbamate - 2-amino-2- (4-pyrimidin-5-ylbutyl) carbamate oxoethyl 4- [6- (4-chlorophenyl) -pyrimidin-4-yl] butylcarbamate 2- (methylamino) -2-oxoethyl -4- [6- (4-chlorophenyl) -2-methyl-pyrimidin-4- il] 2- (methylamino) -2-oxoethyl butylcarbamate -4- [6- (4-chlorophenyl) -2-cyclopropyl-pyrimidin-4-ylbutylcarbamate 2- (methylamino) -2-oxoethyl -4- [6- 2- (Methylamino) -2-oxoethyl - (4-chloro-phenyl) -2- (dimethylamino) -pyrimidin-4-yl] butylcarbamate 2- (methylamino) -2-oxoethyl- (4-quinolin-2-ylbutyl) carbamate 2-amino-2-oxoethyl - ( 4-quinolin- 4-ylbutyl) 2-amino-2-oxoethyl carbamate - 2-amino-2-oxoethyl- (4-isoquinolin-4-ylbutyl) carbamate - 2-amino-2- (4-isoquinolin-1-ylbutyl) carbamate oxoethyl 2- (Methylamino) -2-oxoethyl-4- (3- (4-chlorophenyl) -isoxazol-5-yl] butylcarbamate-2- (4-chlorophenyl) -isoxazol-3-yl] butylcarbamate - (2- (methylamino) -2-oxoethyl-3- (3- (4-phenyl-phenyl) -isoxazol-5-yl] butylcarbamate 2- (2-oxoethyl) -4- [3- (naphthalen-2-methoxy) -2-oxoethyl 2-amino-2-oxoethyl- (5-pyridin-4-ylpentyl) carbamate 2- (methylamino) -2-oxoethyl- (5-pyridin-2-ylpentyl) carbamic acid yl) -isoxazol-5-yl] butylcarbamate of 2-amino-2-oxoethyl - (2-amino-2-oxoethyl) - (5-pyrimidin-5-ylpentyl) carbamate - 2-amino-2-oxoethyl - (5-quinoline-2-ylpentyl) carbamate - (5- quinoline-4-ylpentyl) 2-amino-2-oxoethyl carbamate - 2-amino-2-oxoethyl- (5-isoquinolin-4-ylpentyl) carbamate - (5-isoquinolin-1-ylpentyl) carbamate 2-amino -2-oxoethyl - (2-amino-2-oxoethyl- (3-naphthalen-1-ylprop-2-yn-1-yl) carbamate - (3-naphthalen-1-ylprop-2-yl-carbamic acid) - ( methylamino) -2-oxoethyl- (2-amino-2-oxoethyl- (5-naphthalen-1 -ylpent-4-in-1-yl- (5-naphthalen-1 -ylpent-4-yn-1-yl) carbamate) ) 2- (methylamino) -2-oxoethyl- [5- (4-fluoro-naphthalen-1-yl) -pent-4-yn-1 -yl] carbamic acid 2- (methylamino) -2-oxoethyl carbamate) - [3- (methylamino) -2-oxoethyl- [3- (4-methoxynaphthalen-1-yl) -isoxazol-5-ylpropyl] carbamate [3- (pyridin-3-yl) -isoxazol-5-ylpropyl] carbamic acid of 2- (methylamino) -2-oxoethyl. Among the compounds of general formula (I), a subfamily of compounds consists of compounds that correspond to the general formula (I '): (! ') wherein: A is selected from one or more groups X, Y and / or Z; X represents a methylene group optionally substituted with one or two C1-C6 alkyl, C3-7 cycloalkyl or C3-7 cycloalkyl-C1-3 alkylene groups; Y represents either a C2-alkenylene group optionally substituted with one or two C -6 alkyl, C3-7 cycloalkyl or C3-7 cycloalkyl-C1-3 alkylene groups; either an alkynylene-C2 group; Z represents a group of formula: m represents an integer ranging from 1 to 5; p and q represent integers and are defined so that p + q is a number that goes from 1 to 5; n represents an integer ranging from 1 to 7; Ri represents a group R2 optionally substituted with one or more groups R3 and / or R; R 2 represents a group selected from pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, pyrrolyl, furanyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, naphthalenyl, quinolinyl, tetrahydroquinolinyl, isoquinolinyl, tetrahydroisoquinolinyl, 2-oxo-3,4-dihydroquinolinyl, 1 -oxo-3,4-dihydroisoquinolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, cinolinyl, naphthyridinyl, benzofuranyl, dihydrobenzofuranyl, benzothienyl, dihydrobenzothienyl, indolyl, indolinyl, indazolyl, isoindolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzoxadiazolyl, benzothiadiazolyl, pyrrolopyridinyl, furopyridinyl, thienopyridinyl, imidazopyridinyl, oxazolopyridinyl, thiazolopyridinyl, pyrazolopyridinyl, isoxazolopyridinyl or isothiazolopyridinyl; R3 represents a group chosen from halogen atoms or cyano, nitro, C1-C6 alkyl, C1-6 alkoxy hydroxyl, C1 -6 thioalkyl, C1 -6 fluoroalkyl, C1 -6 fluoroalkoxy, fluorothioalkyl-C groups ? -6, NR5R6, NR5COR6, NR5CO2R6, NR5SO2R6, COR5, CO2R5, CONR5R6, SO2R5, SO2NR5R6, or -O- (C1-3 alkylene) -O; R 4 represents a group selected from the group phenyl, phenyloxy, benzyloxy, naphthalenyl, pyridinyl, pyrimidinyl, pyridazinyl or pyrazinyl; the R4 group (s) may be substituted with one or more R3 groups identical or different from one another; R5 and R6 represent, independently of each other, a hydrogen atom or a C-C6-alkyl group, or form with the atom (s) that contain them a cycle selected from an azetidine, pyrrolidine, piperidine, morpholine, thiomorpholine cycle , azepine or piperazine, this cycle being optionally substituted with a C 1-6 alkyl or benzyl group; R represents a hydrogen atom or a C 1-6 alkyl group; R8 represents a hydrogen atom or a C 1-6 alkyl or C 3-7 cycloalkyl, C 3-7 cycloalkyl-C 1-3 alkyl group. Among the compounds of general formula (I '), a first subgroup of compounds consists of compounds for which: A is chosen from one or more groups X and / or Y; X represents a methylene group; Y represents a C2-alkynylene group; n represents an integer ranging from 1 to 5; R1 represents a group R2 optionally substituted with one or more phenyl groups, more particularly with a phenyl; R 2 represents a group selected from pyridinyl, pyrimidinyl, pyridazinyl, imidazolyl, oxazolyl, oxadiazolyl, naphthalenyl, quinolinyl, isoquinolinyl, dihydroisoquinolinyl, 2-oxo-3,4-dihydroquinolinyl, indolyl, benzimidazolyl or pyrrolopyridinyl; R7 represents a hydrogen atom or a C1-C6 alkyl group; R8 represents a hydrogen atom or a C-6-alkyl, C3-7 cycloalkyl or C3-cycloalkyl, -alkylene-C-? -3 group.

Among the compounds of general formula (I '), a second subgroup of compounds consists of compounds for which: A, n and R1 are as defined in the first subgroup defined above; R7 represents a hydrogen atom; R8 represents a hydrogen atom or a C-C6-alkyl group, more particularly methyl. Among the compounds of general formula (I1), mention may be made of the following compounds: 2- (Methylamino) -2-oxoethyl-2- (5-phenylpyridin-2 - (5-phenylpyridin-2-yl) methyl] carbamic acid 2- (Methylamino) -2-oxoethyl-2- (6-phenylpyridin-3-yl) ethylcarbamate 2- (methylamino) -2-oxoethyl-2- (6-phenylpyridazin-3-yl) ethylcarbamate ethyl) carbamate 2- (Methylamino) -2-oxoethyl 2- (2-phenylpyrimidin-5-yl) ethylcarbamate 2- (methylamino) -2-oxoethyl 2- (5-phenylpyrimidin-2-yl) ethylcarbamate 2- ( 2-methylamino) -2-oxoethyl-2- (4-phenyl-1 / - / - imidazol-1-yl) ethylcarbamate 2-oxoethyl- (2-isoquinolin-7-ylethyl) carbamate - (methylamino) -2-oxoethyl -2- (2-Phenyl-1,3-oxazol-4-yl) ethylcarbamate 2- (methylamino) -2-oxoethyl-2- (5-phenyl-1, 2,4-oxadiazol-3-yl) ethylcarbamate of 2-amino-2-oxoethyl- (3-pyridin-2-ylpropyl) carbamate 2- (2-amino-2-oxoethyl) - (3-pyridin-3-ylpropyl) carbamate 2-amino-2-oxoethyl - ( 2-Amino-2-oxoethyl- (3-pyrimidin-5-ylpropyl) carbamate 2-amino-2-oxoethyl- (3-quinolin-2-ylpropyl) carbamate 2- (3-pyridin-4-ylpropyl) carbamate 2-amino-2-oxoethyl - (3-quinolin-4-ylpropyl) carbamate 2-amino-2-oxoethyl - (3-isoquinolin-1-ylpropyl) carbamate 2-amino-2-oxoethyl - (3-isoquinoline-4-amino-2-oxoethyl) 2-amino-2-oxoethyl-3 - (4-phenyl-1H-imidazole-1-M) propylcarbamate 2- (methylamino) -2-oxoethyl-3- (1 H-benzimidazole-1-carbamic acid) 2- (Methylamino) -2-oxoethyl- (4-pyridin-2-ylbutyl) carbamic acid 2-amino-2-oxoethyl- (4-pyridin-3-ylbutyl) carbamate-2-amino-2-propylcarbamate 2-Amino-2-oxoethyl - (4-pyrimidin-5-ylbutyl) carbamic acid 2-amino-2-oxoethyl- (4-pyridin-4-ylbutyl) carbamate - (4-quinolin-2-ylb) useful) 2-amino-2-oxoethyl carbamate - 2-amino-2-oxoethyl - (4-quinolin-4-ylbutyl) carbamate - 2-amino-2-oxoethyl - (4-isoquinolin-1-ylbutyl) carbamate 2-amino-2-oxoethyl - (2-amino-2-oxoethyl) -4- (1 H-benzimidazol-1-yl) butylcarbamate 2- (methylamino) - (4-isoquinolin-4-ylbutyl) carbamate - 2-Oxoethyl 4- (1 W-indol-1-yl) butylcarbamate of 2- (methylamino) -2-oxoethyl-2-amino-2-oxoethyl-2- (1-indol-1-yl) butylcarbamate - 4- (1-2-amino-2-oxoethyl -4- (1 H -pyrrolo [2,3-o] pyridin-1-yl-pyrrolo [2,3-jb] pyridin-1-yl) butylcarbamate) 2- (methylamino) -2-oxoethyl butylcarbamate -4- (3,4-dihydroisoquinolin-2 (1 H) -yl) butylcarbamate 2- (methylamino) -2-oxoethyl-4- (2-oxo-3, 2-amino-2-oxoethyl-2- (2H) -yl) butylcarbamate 4 - (2-oxo-3,4-dihydroquinolin-1 (2H) -yl) butylcarbamate 2- (methylamino) -2-dihydroquinolin-1 (2H) -yl) butylcarbamate -oxoethyl- (2-amino-2-oxoethyl) 2- (5-pyridin-2-ylpentyl) carbamate - 2-amino-2-oxoethyl- (5-pyrimidin-5-ylpentyl) - (5-pyridin-4-ylpentyl) carbamate 2-amino-2-oxoethyl- (5-quinoline-2-ylpentyl) carbamate 2-amino-2-oxoethyl- (5-quinoline-4-ylpentyl) carbamate 2-amino-2-oxoethyl carbamate - ( 2-amino-2-oxoethyl 5-isoquinolin-1-ylpentyl) carbamate - (2-amino-2-oxoethyl-2- (3-isoquinolin-4-ylpentyl) carbamate - (3-amino-2-oxoethyl - (3-naphthalen-1-ylprop-2-yn-1-yl) carbamic acid) 2- (methylamino) -2-oxoethyl-naphthalene-1-propyl-2-yn-1-yl) carbamic acid - (2-amino-2-oxoethyl- (5-naphthalen-1 -ylpent-4-yn-1-yl) carbamate 2- (5-naphthalen-1 -ylpent-4-yn-1-yl) carbamate methylamino) -2-oxoethyl. The compounds of general formula (I) may comprise one or more asymmetric carbons. They can exist in the form of enantiomers or diastereoisomers. These enantiomers and diastereoisomers, as well as their mixtures, including the racemic mixtures, form part of the invention. The compounds of formula (I) may exist in the form of bases or acid addition salts. Said addition salts form part of the invention. These salts are advantageously prepared with acids acceptable from a pharmaceutical point of view, although salts of other acids useful, for example, for the purification or isolation of the compounds of formula (I) also form part of the invention. The compounds of general formula (I) can be in the form of hydrates or solvates, that is, in the form of associations or combinations with one or more water molecules or with a solvent. Said hydrates and solvates are also part of the invention. In the context of the invention, it is meant by: Ct-Z where tyz can have the values from 1 to 7, a carbon chain which may have from carbon atoms, for example, C1 -3 a carbon chain which may have 1 to 3 atoms of carbon; alkyl, a saturated, linear or branched aliphatic group; for example, an alkyl-C-α-6 group represents a carbon chain of 1 to 6 carbon atoms, straight or branched, more particularly methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertbutyl, pentyl or hexyl; alkylene, a linear or branched saturated divalent alkyl group, for example, an alkylene-C1-3 group represents a divalent carbon chain of 1 to 3 carbon atoms, straight or branched, more particularly methylene, ethylene, 1-methylethylene or propylene; cycloalkyl, a cyclic alkyl group, for example, a C3-7 cycloalkyl group represents a cyclic carbon group of 3 to 7 carbon atoms, more particularly cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl; - alkenylene, a 2-carbon aliphatic, divalent unsaturated group, more particularly ethylene; Alkynylene-C2, a group -C = C-; alkoxy, a linear or branched saturated aliphatic chain-O-alkyl group; - thioalkyl, a saturated or straight or branched aliphatic chain -S-alkyl group; fluoroalkyl, an alkyl group in which one or several hydrogen atoms have been replaced by a fluorine atom; fluoroalkoxy, an alkoxy group in which one or more hydrogen atoms have been replaced by a fluorine atom; fluorothioalkyl, a thioalkyl group in which one or more hydrogen atoms have been replaced by a fluorine atom; halogen atom, fluorine, chlorine, bromine or iodine. The compounds of the invention can be prepared according to different methods, illustrated by the following schemes. Scheme 1 [] n ^ NH, (II) (IV) A first method (scheme 1) for obtaining the compounds of general formula (I) consists in making an amine of general formula (II), in which R,, A and n are as defined in the formula (I), with a carbonate of general formula (III) in which V represents a hydrogen atom or a nitro group, R7 is as defined in the general formula (I) and R represents a methyl or ethyl group . The carbamate ester of general formula (IV) obtained from this way is transformed into a compound of general formula (I), by aminolysis by means of an amine of general formula R8NH2 in which R8 is as defined in general formula (I). The aminolysis reaction can be carried out in a solvent such as methanol or ethanol, or in a mixture of solvents such as methanol and tetrahydrofuran. Another method (scheme 2) to obtain the compounds of general formula (I) is to react a derivative of general formula (V) in which Ri, n and A are as defined in general formula (I) and W represents a hydroxy group, mesylate, tosylate, or a chlorine, bromine or iodine atom, with an oxazolidinedione of general structure (VI) in which R is as defined in general formula (I), provide the oxazolidin-dione derivative of general structure (Vi l). In the case where W represents a hydroxy group, the reaction can be carried out following the conditions of Mitsunobu (Synthesis 1981, 1-28), for example, by the action of diethyl azodicarboxylate or diisopropyl in the presence of triphenylphosphine. In the case where W represents a chlorine, bromine or iodine atom or a mesylate or tosylate group, the reaction can be carried out in the presence of a base such as 1, 1, 3,3-tetramethylguanidine, sodium hydride or sodium butoxide, in a solvent such as tetrahydrofuran, acetonitrile or dimethylformamide at a temperature comprised between 0 ° C and 80 ° C. The oxazolidinedione derivative of the general formula (VI) obtained in this way is converted into a compound of the general formula (I), by aminolysis by an amine of the general formula R8NH2 in which R8 is as defined in general formula (I). Scheme 2 R- [A] n ^ w (V) (Vile) The compounds of general formula (I), (IV) and (Vi l), wherein Ri represents a group of the aryl-aryl, aryl-heteroaryl, heteroaryl-aryl or heteroaryl-heteroaryl type, can also be prepared by reaction of the corresponding compounds of general formula (I), (IV) or (Vil), for which R2 is substituted with a chlorine, bromine, iodine or with a triflate group in the position in which the R4 group must be introduced, with an aryl or heteroaryl boronic acid derivative following the reaction conditions of Suzuki (Chem. Rev. 1995, 95, 2457-2483) or with an aryl or heteroaryl-alkylstannane derivative following the Stille reaction conditions (Angew, Chem. Int. Ed. 1986, 25_, 504-524).

The carbonates of the general formula (11 I) can be prepared according to any method described in the literature, for example, by reacting an alcohol of the general formula HOCHR5COOR in which R represents a methyl or ethyl group with phenyl chloroformate or 4-nitrophenyl , in the presence of a base such as triethylamine or diisopropylethylamine. The compounds of general formula (II), (V) and (VI) as well as the amines of general formula R8NH2, when their mode of preparation is not described, are commercially available or are described in the literature or can be prepared according to different described methods in the literature or known to the person skilled in the art. The compounds of general formula (IV) in which n, A, R- \ and R7 are as defined in the general formula (I) and R represents a methyl or ethyl group are new and also form part of the invention , the following compounds being excluded: -2 - [( { [2- (5-hydroxy-1 H -indol-3-yl) ethyl] amino} carbonyl) -xyxypropanoate ethyl; -2 - [( { [2- [5- (phenylmethoxy) -1 H -indol-3-yl] ethyl} amino) -carbonyljoxy] ethyl propanoate. The compounds of general formula (IV) are useful as synthesis intermediates for the preparation of compounds of general formula (I). The compounds of general formula (VII) in which n, A, R ^ and R7 are as defined in the general formula (I), are new and also form part of the invention, the compounds being excluded following: 2- [2- (2,4-dioxo-3-oxazolidinyl) ethyl] -1-methylpyridinium iodide; 2- [2- (2,4-dioxo-3-oxazolidinyl) etiI] -5-ethyl-1-methylpyridinium iodide; 4- [2- (2,4-dioxo-3-oxazolidinyl) ethyl] -1-methylpyridinium iodide; 5-methyl-3- [2- (4-pyridinyl) ethyl] -2,4-oxazolidinedione hydrochloride; 5-methyl-3- [2- (2-pyridinyl) ethyl] -2,4-oxazolidinedione hydrochloride; -3- (5-imidazo [1,2- a] pyridin-5-ylpentyl) -2,4-oxazolidinedione; -3- [2- (5-methyl-4-thiazolyl) ethyl] -2,4-oxazolidinedione; -3- [2- (1 H-pyrrol-2-yl) ethyl] -2,4-oxazolidinedione; -3- [2- (2-thienyl) ethyl] -2,4-oxazolidinedione; -3- [3- (2-thienyl) propyl] -2,4-oxazolidinedione; -3- [4- (2-thienyl) butyl] -2,4-oxazolidinedione; -5-methyl-3- [2- (2-thienyl) ethyl] -2,4-oxazolidinedione; -5-ethyl-3- [2- (2-thienyl) ethyl] -2,4-oxazolidinedione; -3- [2- (3-thienyl) ethyl] -2,4-oxazolidinedione; -3- [2- (5-methyl-2-thienyl) ethyl] -2,4-oxazolidinedione; -3- [2- (5-acetyl-2-thienyl) ethyl] -2,4-oxazolidinedione; -3- [2- (5-Bromo-2-thienyl) ethyl] -2,4-oxazolidinedione; -5- [2- (2,4-dioxo-3-oxazolidinyl) ethyl] -2-thiophenecarboxaldehyde; -3- [3- (1 -indolinyl) propyl] -2,4-oxazolidinedione; -3- [3- (1-indolinyl) propyl] -5-methyl-2,4-oxazolidinedione; -3- [2- (2-pyridinyl) ethyl] -2,4-oxazolidinedione; -3- [2- (5-ethyl-2-pyridinyl) ethyl] -5-methyl-2,4-oxazolidinedione; -5-ethyl-3- [2- (5-ethyl-2-pyridinyl) ethyl] -2,4-oxazolidinedione; -3- [2- (5-Ethyl-2-pyridinyl) ethyl] -5-isopropyl-2,4-oxazolidinedione; -3- [2- (4-pyridinyl) ethyl] -2,4-oxazolidinedione; -5-ethyl-3- [2- (4-pyridinyl) ethyl] -2,4-oxazolidinedione; -5-ethyl-3- [2- (2-pyridinyl) ethyl] -2,4-oxazolidinedione; -5-isopropyl-3- [2- (4-pyridinyl) ethyl] -2,4-oxazolidinedione; -5-isopropyl-3- [2- (2-pyridinyl) ethyl] -2,4-oxazolidinedione; -3- [2- (5-ethyl-2-pyridinyl) ethyl] -2,4-oxazolidinedione. The compounds of general formula (VII) are useful as synthesis intermediates for the preparation of compounds of general formula (I). A subgroup of compounds of general formula (VII) is composed of compounds for which: n, A, Ri and R7 are as defined in general formula (I) with the proviso that: -when R2 is a group pyrrolyl, imidazo [1,2- a] pyridinyl or indolinyl then R 2 is substituted by one or more groups R 3 and / or R; when R2 is a pyridinyl group, then R2 is substituted with one or more groups R3 and / or R in which R3 is different from methyl or ethyl; when R2 is a thienyl group, then R2 is substituted with one or more groups R3 and / or R4 in which R3 is different from bromine, methyl or from a CHO or COCH3 group; -When R2 is a thiazolyl group substituted with a group R3, then R3 is different from methyl. The examples that follow illustrate the preparation of some compounds of the invention. These examples are not limiting and only serve to illustrate the invention. The microanalysis, the spectra of I. R. and R.M. N. and / or analyzes by LC-MS (Liquid Chromatography coupled with Mass Spectrometry) confirm the structures and purities of the obtained compounds. PF (° C) represents the melting point in degrees Celsius. The numbers indicated in parentheses in the titles of the examples correspond to those in the first column of the following table. Example 1 (compound No. 3) 2-Methylamino-2-oxoethyl 2- (6-phenylpyridin-3-yl) ethylcarbamate eleven . Phenylmethyl 2- (6-phenylpyridin-3-yl) ethylcarbamate To a solution of 4.5 g (25.60 mmoles) of phenylmethyl ethenylcarbamate (Org. Proc. Res. &Develop., 2002, 6, 74- 77) in 25 ml of tetrahydrofuran, cooled to approximately -1 0 ° C, a solution of 3.12 g (12.80 mmoles) of 9-borabicyclo [3.3.1] nonyl is added dropwise under inert atmosphere ( BBN) in 100 ml of tetrahydrofuran maintaining the temperature of the reaction medium lower than -1 0 ° C. Stirring is maintained at -10 ° C for 1 hour, and then at room temperature for 4 hours. 18 ml of an aqueous solution of sodium hydroxide (3N) are added and stirring is maintained for 1 hour. Then, 4.0 g (17.1 mmol) of 5-bromo-2-phenylpyridine and 2.12 g (2.6 mmol) of PdCI2 (dppf) .CH2Cl2 (dppf: 1, 1'-bis) are added. (diphenylphosphino) -ferrocene). Stirring is maintained at room temperature for 18 hours. The reaction mixture is cooled in an ice water bath and 40 ml of a 2/1 mixture of a buffer solution (pH = 7) and 30% hydrogen peroxide are added dropwise. It is left stirring at room temperature for 1 hour. The aqueous phase is separated and extracted three times with dichloromethane. The organic phases are combined and washed successively with water and with a saturated aqueous solution of sodium chloride. The organic phase is dried over sodium sulfate and the filtrate is concentrated under reduced pressure. The residue obtained in this way is purified by chromatography on silica gel eluting with a 20/80 mixture of ethyl acetate and cyclohexane. 2.9 g of product are obtained in the form of a white solid. PF (° C): 1 18 ° C 1 .2. 2- (6-phenylpyridin-3-yl) ethanamine To a solution of 1.8 g (5.42 mmoles) of phenylmethyl 2- (6-phenylpyridin-3-yl) ethylcarbamate, prepared in step 1. 1 . , in 50 ml of dichloromethane, cooled to about 0 ° C, 9 ml of 33% hydrobromic acid in acetic acid are added dropwise. Stirring is maintained at room temperature for 2 hours. It concentrates low reduce pressure and collect the remainder with dichloromethane and with a saturated aqueous solution of sodium hydrogencarbonate. The aqueous phase is separated and extracted twice with ethyl acetate. The organic phases are washed together with a saturated aqueous solution of sodium chloride, dried over sodium sulfate and the filtrate is concentrated under reduced pressure. 0.86 g of product are obtained in the form of an oil which is used as such in the next step. 1 .3. ( { [2- (6-phenylpyridin-3-yl) ethyl] amino.} Carbonyl) -acetic acid ethyl ester A solution of 0.85 g is heated at 60 ° C for 12 hours. (4.29 mmoles) of 2- (6-phenylpyridin-3-yl) ethanamine, prepared in step 1 .2. , and 1.25 g (5.58 mmoles) of ethyl [(phenyloxycarbonyl) oxy] acetate (J. Med. Chem., 1 999, 42, 277-290) in 40 ml of toluene. It is allowed to reach room temperature, the insoluble part is separated by filtration and the filtrate is concentrated under reduced pressure. The residue obtained in this way is purified by chromatography on silica gel eluting with a 30/70 mixture of ethyl acetate and cyclohexane. In this way, 1.06 g of product are obtained in the form of an oil. 1 .4. 2- (Methylamino) -2-oxoethyl 2- (6-phenylpyridin-3-yl) ethylcarbamate To a solution of 1.0 g (3.06 mmol) of ( { [2- (6-phenylpyridin-3 ethyl) amino] ethyl carbonyl) oxyacetate, obtained in step 1 .3. , in 6 ml of methanol, 4.6 ml (9.17 mmoles) of a solution of methylamine (2M) in tetrahydrofuran are added. Stirring is maintained at room temperature for 4 hours. After concentrating under reduced pressure, the residue obtained by chromatography on silica gel eluting with a 95/5 mixture of dichloromethane and methanol. A white solid is obtained which is recrystallized from ethyl acetate. 0.510 g of product are obtained in the form of a white solid. LC-MS: M + H = 314 PF (° C): 130-132 ° C H-NMR1 (CDCl3) d (ppm): 2.85 (d, 3H); 2.95 (t, 2H); 3.55 (q, 2H); 4.60 (s, 2H); 5.05 (broad s, 1 H); 6, 10 (broad s, 1 H); 7.50 (m, 3H); 7.70 (m, 2H); 8.0 (d, 2H); 8.60 (s, 1 H). Example 2 (compound No. 56) 4- (1 H-indol-1-yl) butylcarbamate 2- (methylamino) -2-oxoethyl 2. 1 . 1- (4-bromobutyl) -1H-indole To a solution of 2 g (17.07 mmol) of 1 H-indole and 1.15 ml (51.22 mmol) of 1,4-dibromobutane in 80 ml of dimethylformamide, cooled in a bath of ice water, 0.96 g (17.07 mmol) of sodium hydroxide are added in small portions. The bath is removed and stirring is maintained at room temperature for 1 5 hours. After concentrating under reduced pressure, the residue is taken up with water and ethyl acetate. The aqueous phase is separated, extracted twice with ethyl acetate, the organic phases are washed together with A saturated aqueous solution of sodium chloride is dried over sodium sulfate and the filtrate is concentrated under reduced pressure. The residue obtained in this way is purified by chromatography on silica gel, eluting with a 1/99 mixture of ethyl acetate and cyclohexane. 3 g of product are obtained in the form of a yellow oil. 2. 2. 3- [4- (1 H-indol-1-yl) butyl] -1,3-oxazolidin-2,4-dione A solution of 3 g (1 g) is refluxed for 14 hours under an inert atmosphere. 1.90 mmol) of 1- (4-bromobutyl) -1 H-indoI, prepared in step 2.1. , of 2.41 g (23.80 mmol) of 1,3-oxazolidin-2,4-dione (J. Med. Chem., 1 991, 34, 1 538-1544) and of 2.74 g (23 , 80 mmoles) of 1, 1, 3,3-tetramethylguanidine, in 30 ml of tetrahydrofuran. It is concentrated under reduced pressure. The residue is taken up in ethyl acetate and water, the aqueous phase is separated, extracted twice with ethyl acetate, the organic phases are washed together with a saturated aqueous solution of sodium chloride and dried over sodium sulfate. After evaporation of the solvent, the residue obtained is purified by chromatography on silica gel eluting with a 10/90 and 20/80 mixture of ethyl acetate and cyclohexane. 2 g of product are obtained in the form of a white solid. 2.3. 2- (Methylamino) -2-oxoethyl 4- (1 H-indol-1-yl) butylcarbamate The procedure is as described in example 1 (step 1 .4.). From 0.90 g (3.31 mmol) of 3- [4- (1 H -indol-1-yl) butyl] -1, 3-oxazolidin-2,4-dione, obtained in step 2.2. and 5 ml (9.93 mmoles) of a solution of methylamine (2M) in tetrahydrofuran, and after chromatograph on silica gel eluting with a 98/2 mixture of dichloromethane and methanol to give 0.70 g of product as an amorphous white solid. LC-MS: M + H = 304 PF (° C): 64-67 ° C NMR1H (CDCl 3) d (ppm): 1.50 (m, 2H); 1.90 (m, 2H); 2.80 (d, 3H); 3.20 (q, 2H); 4.20 (t, 2H); 4.55 (s, 2H); 5.95 (broad s, 1H); 6.10 (broad s, 1H); 6.50 (d, 1H); 7.20 (m, 3H); 7.40 (d, 1H); 7.70 (d, 1H). Example 3 (compound No. 71) (2-amino-2-oxoethyl 5-naphthalen-1-ylpent-4-yn-1-yl) carbamate 3. 1.5-naphthalene-1-ylpent-4-yn-1-ol Under an argon atmosphere, a solution of 0.59 g (7 mmol) of 4-pentyin-1-ol in 3 ml of acetonitrile is added dropwise. a suspension of 1.78 g (7 mmol) of 1-iodophthalene of 1.48 ml (10.5 mmol) of triethylamine, 0.066 g (0.35 mmol) of cuprous iodide and 0.147 g (0.21 mmol) of di (triphenylphosphine) palladium dichloride (Ph3P) 2PdCl2 in 4 ml of acetonitrile. Stir 3 hours at room temperature, add 4 g of silica and evaporate to dryness. The product is purified by chromatography on silica gel eluting with an 80/20 and 60/40 mixture of cyclohexane and ethyl acetate to obtain 1.22 g of product as a yellow oil. 3. 2. 5-naphthalen-1-ylpent-4-yn-1-yl methanesulfonate To a solution of 1.2 g (5.71 mmoles) of 5-naphthalen-1-ylpent-4-yn-1-yl, obtained in step 3.1, and of 1.6 ml (11.4 mmol) of triethylamine in 12 ml of dichloromethane, cooled in an ice bath, a solution of 0.85 g (7.42 g) is added dropwise. mmoles) of methanesulfonyl chloride in 5 ml of dichloromethane. Stir 1 hour at 0 ° C and 2 hours at room temperature. 25 ml of water and 75 ml of dichloromethane are added. The organic phase is decanted, washed with 25 ml of water and with 25 ml of a saturated aqueous solution of sodium chloride. Dry over magnesium sulfate and evaporate to dryness to obtain 1, 68 g of product in the form of orange oil, which is used directly in the next stage. 3.3. 3- (5-naphthalen-1 -ylpent-4-yn-1-yl) -1) 3-oxazolidin-2,4-dione. 1.64 g (5.70 mmol) of methanesulfonate of 5-naphthalen-1-ylpent-4-yn-1-yl obtained in step 3.2, and 0J2 g (7.1 mmoles) of 1.3 are dissolved. oxazolidin-2,4-dione in 9 ml of tetrahydrofuran. 1.3 g (11.4 mmol) of 1,1-3,3-tetramethylguanidine in solution in 3 ml of tetrahydrofuran are added. Heat to reflux overnight. 25 ml of ethyl acetate and 6 g of silica are added. It evaporates to dryness. The residue is purified by chromatography on silica gel eluting with a 90/10, 80/20 and 70/30 mixture of cyclohexane and ethyl acetate to obtain 1.33 g of product as a white solid. PF (° C): 99-1 01 ° C 3.4. (2-amino-2-oxoethyl 5-naphthalen-1 -ylpent-4-yn-1-yl) carbamate Dissolve 0.75 g (2.56 mmol) of 3- (5-naphthalen-1 -ylpent-4-yn-1-yl) -1, 3-oxazolidin-2,4-dione obtained in step 3.3, in 1 8 ml of a 7M solution of ammonia (126 mmol) in methanol. Leave overnight at room temperature. 3 g of silica are added and evaporated to dryness. The remainder is purified by chromatography on silica gel eluting with a 98/2, 96/4 and 94/6 mixture of dichloromethane and methanol. It is recrystallized from a mixture of ethyl acetate and diisopropyl ether to obtain 0.59 g of product in the form of white crystals. LC-MS: M + H = 31 1 PF (° C): 1 05-1 08 ° C NMR1H (CDCl 3) d (ppm): 8.33 (d, 1 H); 7.85 (m, 2H); 7.70-7.40 (m, 4H); 5.90 (broad m, 1 H); 5.50 (broad m, 1 H); 5.20 (broad m, 1 H); 4.55 (s, 2H); 3.50 (m, 2H); 2.70 (t, 2H); 1.95 (m, 2H). Example 4 (compound No. 29) 2- (methylamino) -2-oxoethyl 3- (3- (4-chlorophenyl) isoxazol-5-yl] propyl) carbamate 4. 1 . 3- [3- (4-chlorophenyl) isoxazol-5-yl] propan-1 -ol 1.6 ml (11.5 mmol) of triethylamine are added dropwise to a solution of 1.18 ml (12 ml). 6 mmole) of pent-4-in-1 -ol and 2.0 g (10.5 mmoles) of 4-chloro-N-hydroxybenzenecarboximidoyl chloride (J. Med. Chem. 1998, 41, 4556-4566) in 30 ml of dichloromethane cooled in an ice bath. It is left to react overnight at room temperature. 50 ml of dichloromethane and 70 ml of water are added. The organic phase is separated and the aqueous phase is extracted twice with 50 ml of dichloromethane. The organic phases are washed twice with 70 ml of water and 70 ml of a saturated aqueous solution of sodium chloride, dried over sodium sulphate and evaporated. The remainder is purified by chromatography on silica gel eluting with a mixture of cyclohexane and ethyl acetate to obtain 1.3 g (5.47 mmol) of product as a white solid. PF (° C): 60-62 ° C 4.2. 3-. { 3- [3- (4-chlorophenyl) isoxazol-5-yl] propyl} -1, 3-oxazolidin-2,4-dione To a solution of 1.30 g (5.47 mmol) of 3- [3- (4-chlorophenyl) isoxazol-5-yl] propan-1-ol, prepared In step 4.1, and 0.9 ml (7.1 mmol) of triethylamine in 70 ml of dichloromethane, cooled in an ice bath, 0.5 ml (6.0 mmol) of the mixture is added dropwise. methanesulfonyl chloride. Stir 2 hours at room temperature. 70 ml of water are added and the organic phase is separated. The aqueous phase is extracted twice with 70 ml of dichloromethane. The organic phases are washed with 100 ml of water and 100 ml of a saturated aqueous solution of sodium chloride, dried over sodium sulphate and evaporated. The residue is redissolved in 60 ml of tetrahydrofuran and 0.9 g (8.9 mmoles) of 1,3-oxazolidin-2,4-dione and 1.1 ml (8.7 mmoles) of 1.1 are added. 3,3-tetramethylguanidine. It is heated at 65 ° C overnight. It is collected in a mixture of 100 ml of water and 100 ml of ethyl acetate. The organic phase is separated and the aqueous phase is extracted twice with 80 ml of ethyl acetate. The organic phases are washed with 100 ml of water and 1000 ml of a saturated aqueous solution of sodium chloride, dried over sodium sulphate and evaporated. The residue is purified by chromatography on silica gel eluting with a 90.5 / 0.5 mixture of dichloromethane and methanol to obtain 1.0 g (3.1 mmol) of product as a white solid. 4.3. . { 3- [3- (4-chlorophenyl) isoxazol-5-yl] propyl} 2- (methylamino) -2-oxoethyl carbamate 0.6 g (1.87 mmol) of 3- are dissolved. { 3- [3- (4-chlorophenyl) isoxazol-5-yl] propyl} -1, 3-oxazolidin-2,4-dione, prepared in step 4.2. , in a mixture of 8 ml of tetrahydrofuran and 15 ml of methanol. 2.8 ml of a 2M solution of methylamine (5.6 mmol) in tetrahydrofuran are added. It is left to react overnight at room temperature and evaporated. The remainder is purified by chromatography on silica gel eluting with a 98/2, 95/5 and 90/10 mixture of dichloromethane and methanol. It is recrystallized from a mixture of ethyl acetate and methanol to obtain 0.49 g (1.4 mmol) of white crystals. LC-MS: M + H = 352 PF (° C): 158-160 ° C H-NMR1 (CDCl3) d (ppm): 7.75 (d, 2H); 7.45 (d, 2H); 6.35 (s, 1 HOUR); 6, 10 (broad s, 1 H); 5.00 (broad s, 1 H); 4.60 (s, 2H); 3.35 (m, 2H); 2.85 (m + d, 5H); 2.05 (m, 2H). Example 5 (compound No. 20) 2- (methylamino) -2-oxoethyl 3- (6- (4-chlorophenyl) pyrimidin-4-yl] propyl) carbamate . 1 . 1- (4-chlorophenyl) -6- (tetrahydro-2 / -pyran-2-yloxy) hex-2-in- 1-ol To a solution of 13.25 g (78.8 mmol) of 2- ( pent-4-in-1-yloxy) tetrahydro-2-pyran in 130 mL of anhydrous tetrahydrofuran cooled to -78 ° C under argon, 61.5 mL of a solution of n-butyllithium 1.6 are added dropwise. M (98.4 mmol) in hexane. Stirring is maintained for 1 hour at -78 ° C and a solution of 12.18 g (86.6 mmol) of 4-chlorobenzaldehyde in 40 ml of tetrahydrofuran is added dropwise. Stirring is maintained for 2 hours at -78 ° C, the solution is reheated to 0 ° C and poured into 300 ml of a saturated aqueous solution of ammonium chloride. It is extracted with 450 ml of ethyl acetate. The organic phase is washed with 50 ml of water and with 50 ml of a saturated aqueous solution of sodium chloride. Dry over sodium sulfate and evaporate. The remainder is purified by chromatography on silica gel eluting with a 70/30 mixture of n-hexane and ethyl acetate to obtain 6.64 g (53.38 mmol) of product as a colorless oil. 5.2. 1- (4-chlorophenyl) -6- (tetrahydro-2 / - / - pyran-2-yloxy) hex-2-in-1 -one A solution of 16.60 g (53.7 mmol) is added dropwise. ) of 1- (4-chlorophenyl) -6- (tetrahydro-2-pyran-2-yloxy) hex-2-in-1 -ol, prepared in step 5.1. , to a suspension of 93 g (1.07 moles) of manganese dioxide in 500 ml of dichloromethane cooled in an ice bath. Stirring is maintained for 1.5 hours, filtered over celite and washed with dichloromethane. The filtrates are evaporated to obtain 16.3 g (53.1 mmol) of product in the form of a yellowish oil. 5.3 4- (4-chlorophenyl) -6- [3- (tetrahydro-2 / - / - pyran-2-yloxy) propyl] pyrimidine A mixture of 3.60 g (1 liter) is stirred at 40 ° C for 5 hours. , 73 mmoles) of 1- (4-chlorophenyl) -6- (tetrahydro-2H-pyran-2-yloxy) hex-2-in-1 -one, prepared in step 5.2. , of 9.45 g (1-1.7 mmol) of formamidine hydrochloride and of 25 g (234 mmol) of sodium carbonate in suspension in 1 08 ml of acetonitrile and 0.1 ml of water. It is collected with 600 ml of water and 400 ml of a saturated aqueous solution of sodium carbonate. The organic phase is decanted, washed with 200 ml of water and 200 ml of a saturated aqueous solution of sodium chloride, dried over sodium sulphate and evaporated. The residue is purified by chromatography on silica gel eluting with a 70/30 mixture of n-hexane and ethyl acetate to obtain 3.22 g (9.67 mmol) of product in the form of a yellowish oil. 5.4. 3- [6- (4-chlorophenyl) pyrimidin-4-yl] propan-1 -ol 3.22 g (9.67 mmol) of 4- (4-chlorophenyl) -6- [3- (tetrahydro- 2H-pyran-2-yloxy) propyl] pyrimidine, prepared in step 5.3., In 32 ml of methanol and 16 ml of a solution of 4N hydrochloric acid in dioxane are added. The mixture is stirred at room temperature for 1.5 hours and 150 ml of a half-saturated aqueous sodium hydrogencarbonate solution are added. It is extracted with 350 ml of ethyl acetate.

The organic phase is washed with 50 ml of water and 50 ml of a saturated aqueous solution of sodium chloride, dried over sodium sulphate and evaporated to obtain 2.33 g (9.36 mmol) of product as a solid. White. PF (° C): 75-76 ° C 5.5. 3-. { 3- [6- (4-chlorophenyl) pyrimidin-4-yl] propyl} -1, 3-oxazolidin-2,4-dione To a solution of 0.1 1 g (0.44 mmoles) of 3- [6- (4-chlorophenyl) pyrimidin-4-yl] propan-1-ol , prepared in step 5.4. of 0,077 g (0,76 mmoles) of 1,3-oxazolidin-2,4-dione and 0,235 g (0,89 mmoles) of triphenylphosphine in 4 ml of tetrahydrofuran, cooled in an ice bath, are added 0 , 4 ml of a 40% solution of diethyl azodicarboxylate (0.9 mmol) in toluene. Stir overnight at room temperature. It is collected by a mixture of ethyl acetate and water. The organic phase is washed with a saturated aqueous solution of sodium chloride, it is dried over sodium sulphate and evaporated. The remainder was purified by chromatography on silica gel eluting with a 97/3 mixture of dichloromethane and methanol to obtain 0.17 g (0.35 mmol) of product as a solid. 5.6. . { 3- [6- (4-chlorophenyl) pyrimidin-4-yl] propyl} 2- (methylamino) -2-oxoethyl carbamate 0.13 g (0.34 mmol) of 3- are redissolved. { 3- [6- (4-chlorophenyl) pyrimidin-4-yl] propyl} -1, 3-oxazolidin-2,4-dione, prepared in step 5.5. , in a mixture of 4 ml of ethanol, 1 ml of methanol and 1 ml of dichloromethane. 2 ml of an 8 M solution of methylamine (16 mmoles) in ethanol. It is stirred for 2 hours at room temperature and evaporated. The solid residue is collected by diethyl ether to obtain 0.127 g (0.34 mmol) of product as a white solid. LC-MS: M + H = 363 PF (° C): 147-149 ° C 1 H NMR (CDCl 3) d (ppm): 9, 15 (s, 1 H); 8.05 (d, 2H); 7.65 (s, 1 H); 7.55 (d, 2H); 6, 15 (broad s, 1 H); 5.30 (broad s, 1 H); 4.55 (s, 2H); 3.35 (m, 2H); 2.85 (m + d, 5H); 2, 1 0 (m, 2H). Table 1 below illustrates the chemical structures and physical properties of some compounds according to the invention. In this table: all the compounds are in the form of free base, -i-propyl, n-butyl and t-butyl represent, respectively, the isopropyl, linear butyl and tertiary butyl groups. Table 1 (l) The compounds of the invention have been the target of pharmacological tests that allow to determine their inhibitory effect on the FAAH (Fatty Acid amido Hydrolase) enzyme. The inhibitory activity has been demonstrated in a radioenzymatic assay based on the determination of the product of hydrolysis (ethanolamine [1 -3H]) of anandamide [ethanolamine 1 -3H] by FAAH. { Life Sciences (1995), 56, 1999-2005 and Journal of Pharmacology and Experimental Therapeutics (1997), 283, 729-734). Thus, mouse brains (minus the cerebellum) are removed and stored at -80 ° C. The membrane homogenates are prepared extemporaneously by homogenizing the tissues with a Polytron in a 10 mM Tris-HCl buffer (pH 8.0) containing 150 mM NaCl and 1 mM EDTA. The enzymatic reaction is then carried out in 70 μl of buffer containing bovine serum albumin without fatty acids (1 mg / ml). In succession, the compounds tested in different concentrations were added, anandamide [ethanolamine 1 -3H] (specific activity 15-20 Ci / mmol) diluted to 10 μM with cold anandamide and the membrane preparation (400 μg frozen tissue per test). ). After 15 minutes at 25 ° C, the enzymatic reaction is stopped by addition of 140 μl of chloroform / methanol (2: 1). The mixture is stirred 10 minutes and centrifuged for 1 5 minutes at 3500g. An aliquot (30 μl) of the aqueous phase containing the ethanolamine [1 -3 H] is counted by liquid scintillation. Under these conditions, the most active compounds of the invention have values of Cl50 (concentration that inhibits 50% of the control enzymatic activity of the FAAH) comprised between 0.001 and 1 μM. For example, compound No. 68 of the table presents a IC 50 of 0.267 μM. It appears, therefore, that the compounds according to the invention have an inhibitory activity on the FAAH enzyme. The in vivo activity of the compounds of the invention has been evaluated in an analgesic assay.

Thus, intraperitoneal (ip) administration of PBQ (phenylbenzoquinone, 2 mg / kg in a 0.9% sodium chloride solution containing 5% ethanol) to male OF1 rats from 25 to 30 g, causes abdominal stretches, Twists or contractions of average during the period of 5 to 15 minutes after the injection. The tested compounds are administered orally (p.o.) or intraperitoneally (i.p.) in suspension in 0.5% Tween 80, 60 minutes or 120 minutes before administration of PBQ. Under these conditions, the most potent compounds of the invention reduce from 35 to 70% the number of stretches induced by PBQ, in a dose range comprised between 1 and 30 mg / kg. For example, compound No. 48 of the table reduces 53% and 62% the number of stretches induced by PBQ, at the dose 10 mg / kg p.o. respectively at 60 minutes and 120 minutes. The FAAH enzyme. { Chemistry and Physics of Lipids, (2000), 108, 1 07-121) catalyzes the hydrolysis of the endogenous derivatives of amides and esters of different fatty acids such as? / - arachidonoylethanolamine (anandamide),? / - palmtoxylethanolamine,? / - oleoylethanolamine, oleamide or 2-arachidonoylglycerol . These derivatives exert different pharmacological activities interacting, among others, with the cannabinoid and vanilloid receptors. The compounds of the invention block this degradation pathway and increase the tissue rate of these endogenous substances.

They can be used in this way in the prevention and treatment of pathologies in which endogenous cannabinoids are involved and / or any other substrate metabolized by the FAAH enzyme. For example, the following diseases and conditions can be mentioned: Pain, mainly acute or chronic neurogenic pains: migraine, neuropathic pain including the forms associated with the herpes virus and diabetes; Acute or chronic pains associated with inflammatory diseases: arthritis, rheumatoid arthritis, osteoarthritis, spondylitis, gout, vascularitis, Crohn's disease, irritable bowel syndrome; acute or chronic peripheral pain; dizziness, vomiting, nausea in particular those resulting from chemotherapy; eating behavior disorders in particular anorexia and cachexia of different natures; neurological and psychiatric pathologies: tremors, dyskinesias, dystonia, spasticity, compulsive and obsessive behaviors, Tourette syndrome, all forms of depression and anxiety of any nature and origin, mood disorders, psychosis; Acute and chronic neurodegenerative diseases: Parkinson's disease, Alzheimer's disease, senile dementia, Huntington's chorea, lesions linked to cerebral ischemia and cranial and spinal injuries; epilepsy; sleep disorders including sleep apneas; cardiovascular diseases in particular hypertension, cardiac arrhythmias, arteriosclerosis, cardiac crisis, cardiac ischemia; renal ischemia; cancers: benign skin tumors, papillomas and brain tumors, tumors of the prostate, brain tumors (glioblastomas, medulloepitheliomas, medulloblastomas, neuroblastomas, tumors of embryonic origin, astrocytomas, astroblastomas, ependiomas, oligodendrogliomas, plexus tumor, neuroepitheliomas, tumor the epiphysis, ependymoblastomas, malignant meningiomas, sarcomatosis, malignant melanomas, schwannomas); disorders of the immune system, mainly autoimmune diseases: psoriasis, lupus erythematosus, connective tissue diseases or connective tissue disease, Sjogren syndrome, ankylosing spondylitis, undifferentiated spondylarthritis, Behcet's disease, autoimmune hemolytic anemias, sclerosis in plaques, amyotrophic lateral sclerosis , amyloidosis, rejection of grafts, diseases that affect the plasmocitary line; allergic diseases: immediate or delayed hypersensitivity, allergic rhinitis or conjunctivitis, contact dermatitis; infectious parasitic, viral or bacterial diseases: AIDS, meningitis; inflammatory diseases, mainly joint diseases: arthritis, rheumatoid arthritis, osteoarthritis, spondylitis, gout, vascularitis, Crohn's disease, irritable bowel syndrome; osteoporosis; ocular conditions: ocular hypertension, glaucoma; pulmonary conditions: diseases of the ways respiratory, bronchospasm, cough, asthma, chronic bronchitis, chronic obstruction of the respiratory tract, emphysema; gastro-intestinal diseases: irritable bowel syndrome, inflammatory bowel disorders, ulcers, diarrhea; urinary incontinence and bladder inflammation. The use of a compound of formula (I), in the form of a base, of salt, hydrate or solvate acceptable from a pharmaceutical point of view, for the preparation of a medicament intended to treat the aforementioned pathologies forms an integral part of the invention. The invention also relates to medicaments comprising a compound of formula (I), or a salt, or alternatively a pharmaceutically acceptable hydrate or solvate of the compound of formula (I). These drugs find application in therapy, mainly in the treatment of the aforementioned pathologies. According to another of its aspects, the present invention relates to pharmaceutical compositions containing, as active ingredient, at least one compound according to the invention. These pharmaceutical compositions contain an effective dose of a compound according to the invention, or a salt, or a hydrate, or a pharmaceutically acceptable solvate of said compound, and optionally one or more pharmaceutically acceptable excipients. Said excipients are selected according to the pharmaceutical form and the desired mode of administration among the usual excipients which they are known to those skilled in the art. In the pharmaceutical compositions of the present invention for oral, sublingual, subcutaneous, intramuscular, intravenous, topical, local, intrathecal, intranasal, transdermal, pulmonary, ocular or rectal administration, the active ingredient of formula (I) above, or its salt , optional solvate or hydrate, can be administered in unitary administration form or mixed with conventional pharmaceutical excipients, animals and humans for the prophylaxis or treatment of the disorders or diseases mentioned above. Suitable unit dosage forms comprise oral forms, such as tablets, soft or hard capsules, powders, granules, chewing gums and oral solutions or suspensions, sublingual, buccal, intratracheal, intraocular, intranasal, inhalation, forms of subcutaneous, intramuscular or intravenous administration, and forms of rectal or vaginal administration. For topical application, the compounds according to the invention can be used in creams, ointments or lotions. By way of example, a unitary form of administration of a compound according to the invention in the tablet form can comprise the following components: Compound according to the invention 50.0 mg Mannitol 223.75 mg Croscarmellose sodium 6.0 mg Corn starch 15 , 0 mg Hydroxypropyl methylcellulose 2.25 mg Magnesium stearate 3.0 mg 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 galenic form. There may be particular cases in which higher or lower doses are appropriate, said doses also belonging to the invention. According to the usual practice, the appropriate dosage for each patient is determined by the doctor according to the mode of administration, the weight and the response of said patient. The invention according to another of its aspects, also refers to a method of treating the aforementioned pathologies comprising the administration of an effective dose of a compound according to the invention, one of its pharmaceutically acceptable salts, a solvate or a hydrate of said compound.

Claims (12)

1. CLAIMS 1. Compound that corresponds to the general formula (I) (I) wherein: A is selected from one or more groups X, Y and / or Z; X represents a methylene group optionally substituted with one or two C 1 -C 6 -alkyl, C 3-7 cycloalkyl or C 3-7 cycloalkyl-C 1-3 -alkylene groups; Y represents either a C2-alkenylene group optionally substituted with one or two C1-6 alkyl, C3-7 cycloalkyl or C3-7 cycloalkyl-C1-3 alkylene groups; either an alkynylene-C2 group; Z represents a group of formula: m represents an integer ranging from 1 to 5; p and q represent integers and are defined so that p + q is a number that goes from 1 to 5; n represents an integer ranging from 1 to 7; Ri represents a group R2 optionally substituted with one or more groups R3 and / or R4; R 2 represents a group selected from pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, pyrrolyl, furanyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, naphthalenyl, quinolinyl, tetrahydroquinolinyl, isoquinolinyl, tetrahydroisoquinolinyl, 2-oxo-3,4-dihydroquinolinyl, 1 -oxo-3,4-dihydroisoquinolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, cinolinyl, naphthyridinyl, benzofuranyl, dihydrobenzofuranyl, benzothienyl, dihydrobenzothienyl, indolyl, indolinyl, indazolyl, isoindolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzoxadiazolyl, benzothiadiazolyl, pyrrolopyridinyl, furopyridinyl, thienopyridinyl, imidazopyridinyl, oxazolopyridinyl, thiazolopyridinyl, pyrazolopyridinyl, isoxazolopyridinyl or isothiazolopyridinyl; R3 represents a group selected from halogen atoms, cyano, nitro, C6-alkyl, C3-cycloalkyl, C1-6-alkoxy, hydroxyl, fluoroalkyl-C1-6, fluoroalkoxy-C1 -6, fluorothioalkyl-C? -6, NR5R6, NR5COR6, NR5CO2R6, NR5SO2R6, COR5, CO2R5, CONR5R6, SO2R5, SO2NR5R6, -O- (alkylene-C1-3) -O and phenyl, the phenyl group being optionally substituted with one or more halogen atoms; R represents a group selected from the group phenyl, phenyloxy, benzyloxy, naphthalenyl, pyridinyl, pyrimidinyl, pyridazinyl or pyrazinyl; the R4 group (s) having one or more R3 groups identical or different from one another may be substituted; Rs and Re represent independently of one another a hydrogen atom or a C1-C6 alkyl group, or form with the atoms containing them a cycle chosen from an azetidine, pyrrolidine, piperidine, morpholine, thiomorpholine, azepine or piperazine cycle, this cycle optionally being substituted with a C 1-6 alkyl or benzyl group; R7 represents a hydrogen atom or a C1-C6 alkyl group; R8 represents a hydrogen atom or a C1-C6 alkyl or C3-7 cycloalkyl, cycloalkyl-Cs-7-alkylen-C-? _3 group; in the form of a base, of addition salt with an acid, hydrate or solvate. Compound of formula (I) according to claim 1, characterized in that: A is chosen from one or several groups X and / or Y; X represents a methylene group; Y represents a C2-alkynylene group; n represents an integer ranging from 1 to 5; RT represents a group R2 optionally substituted with one or more groups R3 and / or R; R 2 represents a group chosen from pyridinyl, pyrimidinyl, pyridazinyl, imidazolyl, oxazolyl, pyrazolyl, isoxazolyl, oxadiazolyl, naphthalenyl, quinolinyl, isoquinolinyl, dihydroisoquinolinyl, 2-oxo-3,4-dihydroquinolinyl, indolyl, benzimidazolyl or pyrrolopyridinyl; R 3 represents a group selected from halogen atoms, C 1-6 alkyl, C 3-7 cycloalkyl, C 1-6 alkoxy, NR 5 R 6 and phenyl groups; R4 represents a group chosen from the phenyl, naphthalenyl or pyridinyl groups; the R4 group (s) can be substituted one or several R3 groups identical or different from one another; R5 and R6 independently represent a C1-C6 alkyl group; R7 represents a hydrogen atom or a C1-C6 alkyl group; R8 represents a hydrogen atom or a C1-6 alkyl, C3-7 cycloalkyl or C3.7-cycloalkyl-d -3-alkylene group; in the form of a base, of addition salt with an acid, hydrate or solvate. 3. Compound of formula (I) according to any of claims 1 or 2, characterized in that: R2 represents a group chosen from pyridinyl, pyrimidinyl, oxazolyl, isoxazolyl, naphthalenyl, quinolinyl or isoquinolinyl. 4. Compound of formula (I) according to any one of claims 1 to 3, characterized in that: R7 represents a hydrogen atom; R8 represents a hydrogen atom or a C1-C6 alkyl group; in the form of a base, of addition salt with an acid, hydrate or solvate. 5. Process for the preparation of a compound of formula (I) according to any one of claims 1 to 4, comprising the step of converting the carbamate ester of the general formula (IV) wherein A, n, R1 and R7 are as defined in formula (I) according to claim 1 and R represents a methyl group or ethyl, by aminolysis by an amine of general formula R8NH2 wherein R8 is as defined in formula (I) according to claim 1. 6. Process for the preparation of a compound of formula (I) according to any one of claims 1 to 4, comprising step which consists of transforming the oxazolidinedione derivative of the general formula (VII) in which A, n, Ri and R7 are such as defined in the formula (I) according to claim 1, by aminolysis by means of an amine of the formula R8NH2 wherein R8 is as defined in formula (I) according to claim 1. 7. Compound that corresponds to the general formula (IV), wherein A, n, Ri and R7 are as defined in formula (I) according to claim 1 and R represents a methyl or ethyl group, the following compounds being excluded: -2 - [( { [ Ethyl 2- (5-hydroxy-1 H -indol-3-yl) ethyl] amino.} Carbonyl) -oxijpropanoate; -2 - [( { [2- [5- (phenylmethoxy) -1 H -indol-3-yl] ethyl.}. Amino) - carbonyl] oxy] ethyl propanoate. 8. Compound that responds to the general formula (VII), wherein A, n, Ri and R7 are as defined in formula (I) according to claim 1, the following compounds being excluded: 2- [2- (2,4-dioxo-3-) iodide oxazolidinyl) ethyl] -1-methylpyridinium; 2- [2- (2,4-dioxo-3-oxazolidinyl) ethyl] -5-ethyl-1-methylpyridinium iodide; 4- [2- (2,4-dioxo-3-oxazolidinyl) ethyl] -1-methylpyridinium iodide; 5-methyl-3- [2- (4-pyridinyl) ethyl] -2,4-oxazolidinedione hydrochloride; 5-methyl-3- [2- (2-pyridinyl) ethyl] -2,4-oxazolidinedione hydrochloride; -3- (5-imidazo [1,2- a] pyridin-5-ylpentyl) -2,4-oxazolidinedione; -3- [2- (5-methyl-4-thiazolyl) ethyl] -2,4-oxazole dinandone; -3- [2- (1 H-pyrrol-2-yl) ethyl] -2,4-oxazolidinedione; -3- [2- (2-thienyl) ethyl] -2,4-oxazolidinedione; -3- [3- (2-thienyl) propyl] -2,4-oxazolidinedione; -3- [4- (2-thienyl) butyl] -2,4-oxazolidinedione; -5-methyl-3- [2- (2-thienyl) ethyl] -2,4-oxazolidinedione; -5-ethyl-3- [2- (2-thienyl) ethyl] -2,4-oxazolidinedione; -3- [2- (3-thienyl) ethyl] -2,4-oxazolidinedione; -3- [2- (5-methyl-2-thienyl) ethyl] -2,4-oxazolidinedione; -3- [2- (5-acetyl-2-thienyl) ethyl] -2,4-oxazolidinedione; -3- [2- (5-Bromo-2-thienyl) ethyl] -2,4-oxazolidinedione; -5- [2- (2,4-dioxo-3-oxazolidinyl) ethyl] -2-thiophenecarboxaldehyde; -3- [3- (1 -indolinyl) propyl] -2,4-oxazolidinedione; -3- [3- (1-indolenyl) propyl] -5-methyl-2,4-oxazolidinedione; -3- [2- (2-pyridinyl) ethyl] -2,4-oxazolidinedione; -3- [2- (5-ethyl-2-pyridinyl) ethyl] -5-methyl-2,4-oxazolidinedione; -5-ethyl-3- [2- (5-ethyl-2-pyridinyl) ethyl] -2,4-oxazolidinedione; -3- [2- (5-ethyl-2-pyridinyl) ethyl] -5-isopropyl-2,4-oxazolidinedione; -3- [2- (4-pyridinyl) ethyl] -2,4-oxazolidinedione; -5-ethyl-3- [2- (4-pyridinyl) ethyl] -2,4-oxazolidinedione; -5-ethyl-3- [2- (2-pyridinyl) ethyl] -2,4-oxazolidinedione; -5-isopropyl-3- [2- (4-pyridinyl) ethyl] -2,4-oxazolidinedione; -5-isopropyl-3- [2- (2-pyridinyl) ethyl] -2,4-oxazolidinedione; -3- [2- (5-ethyl-2-pyridinyl) ethyl] -2,4-oxazolidinedione. 9. A pharmaceutical composition comprising at least one compound of formula (I) according to any one of claims 1 to 4, in pharmaceutically acceptable base, salt, hydrate or solvate form and optionally one or more acceptable excipients from a pharmaceutical point of view. 10. Compound of formula (I) according to any one of claims 1 to 4, in the form of a base, salt, hydrate or solvate acceptable from a pharmaceutical point of view, for use as a medicine. eleven . Use of a compound of formula (I) according to any one of claims 1 to 4, in pharmaceutically acceptable base, salt, hydrate or solvate form, for the preparation of a medicament intended to prevent or treat a pathology in which endogenous cannabinoids and / or any other substrate metabolized by the FAAH enzyme are involved. 12. Use of a compound of formula (I) according to any one of claims 1 to 4in the form of a base, salt, hydrate or solvate acceptable from a pharmaceutical point of view, for the preparation of a medicament intended to prevent or treat acute or chronic pain, dizziness, vomiting, nausea, eating behavior disorders, neurological and psychiatric pathologies, acute or chronic neurodegenerative diseases, epilepsy, sleep disorders, cardiovascular diseases, renal ischemia, cancers, immune system disorders, allergic diseases, infectious parasitic, viral or bacterial diseases, inflammatory diseases, osteoporosis, ocular affections , pulmonary affections, gastro-intestinal diseases or urinary incontinence.