BR102012019586A2 - alkyl heterocycle carbamate derivatives, their preparation and their therapeutic application - Google Patents

Abstract

alkyl heterocycle carbamate derivatives, their preparation and their therapeutic application. The invention relates to the compounds corresponding to the general formula (1): wherein r2 represents a hydrogen, fluorine, hydroxyl, damage, trifluoromethyl, C1-4 alkyl, c14-alkoxy or -nr8r9; n and m independently represent an integer equal to 1, 2 or 3, the sum being m + n being at most 5; a represents a covalent bond, an oxygen, a C14-alkylene or -o-C1-6 alkylene; R1 represents a phenyl or a heterocycle which is optionally substituted; R3 represents hydrogen, fluorine, C14-alkyl or trifluoromethyl; R4 represents an optionally substituted 5-membered heterocycle; in the form of the base or an addition salt with an acid; excluding 5-methylisoxazol-3-ylmethyl 4-hydroxy-4- (4-chlorophenyl) piperidyl-1-carboxylate. The invention also relates to a process for the preparation of the compounds of formula (1), the compositions comprising them and their therapeutic application.

Description

Report of the Invention Patent for "ALKYL HYPEROCYCLE CARBAMATE DERIVATIVES, THEIR PREPARATION AND THERAPEUTIC APPLICATION".

One subject matter of the invention is alkyl heterocycle carbamate derivatives, their preparation and their therapeutic application.

In this context there is still a need to discover and develop products that are FAAH (Fatty Acid Hydrolase) enzyme inhibitors. The compounds of the invention achieve this goal.

In addition, these compounds must exhibit metabolic and pharmacokinetic properties and a safety index that allow them to be used as medicines.

The compounds of the invention correspond to the general formula (I): wherein:. R2 represents a hydrogen or fluorine atom or a hydroxyl, cyano, trifluoromethyl, C1-6 alkyl, C1-6 alkoxy or -NRe R6 group; - and, independently of each other, do not represent an integer of 1, 2 or 3, the sum being m + n being at most 5; - A represents a covalent bond, an oxygen atom, a C1-6 alkylene group or a -0-C1-6 alkylene group wherein the end represented by an oxygen atom is attached to the group R-i; R1 represents a group R5 optionally substituted by one or more groups R6 and / or R7; R5 representing a chosen group of phenyl, pyridinyl, pyridinyl, pyrimidinyl, pyrazinyl, triazinyl, naphthyl, quinolinyl, isoquinolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, cinolinyl, naphthyridinyl, benzothiazolyl, benzoxazol, benzoxazol isobenzofuranila, benzofuranyl, benzotiofenila, benzotiadiazolila, benzoxadiazolila, indazolila, indolizinila, indolyl, isoindolila, imidazopiridinila, imidazopirimidinila, imidazo-pyrazinyl, imidazopiridazinila, triazolopiridinila, pirrolopiridinila, pirrolopirimidi-nila, pirrolopirazinila, pirrolopiridazinila, pirrolotriazinila, pirazolopiridinila pi-razolopirimidinila, pirazolopirazinila, pyrazolopyridazinyl, furopyridinyl, furopyrimidinyl, furopyrazinyl, furopiridazinyl, furotriazinyl, oxazolopyridinyl, oxazolopyrimidinyl, oxazolopyrazinyl, oxazolopyridazinyl, isoxazolopyridinyl, isoopyrazolazole la, thienopyridinyl, thienopyrimidinyl, thienopyrazinyl, thienopyridazinyl, thienotriazinyl, thiazolopyridinyl, thiazolopyrimidinyl, thiazolopyridazinyl, thiazolopyridazinyl, isothiazolopyridinyl thiazolyridazinyl, isothiazolyridazinyl

Re represents a halogen atom or a cyano group, -CH 2 CN, nitro, hydroxyl, C 1-8 alkyl, C 1-6 alkoxy, C 1-6 thioalkyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 1-6 -halothioalkyl, C 3-7 -cycloalkyl, C 3-7 -cycloC 1-3 alkylene, C 3-7 cycloalkylC 1-3 alkylene-O-, (CH 2) P-NR 8 R 9, -NReCORg, -NR 8 CO 2 R 9i -NR 8 SO 2 R 9j - NR8SO2NR8R9, -COR8i-CO2Rs, - (CH2) p-CONR8R9, -SO2R8i -SO2NR8R9 or -CHC4-alkylene-J-; R 7 representing a group selected from phenyl, phenyl-C 1-4 alkylene-, phenyl- (CH 2) p -0-, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, furanyl, thienyl, imidazolyl, oxazolyl, isoxazolyl, pyrrolyl, pyrazolyl, te-bringsolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, imidazopyrimidinyl, thienopyrimidinyl, benzofuranyl, benzothienyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, pyridylazole, indolylidazinyl, pyridylimidazole oxazolopyridinyl, isoxazolopyridinyl or thiazolopyridinyl; being possible for the group or groups R7 to be substituted by one or more groups R6 which are identical to or different from each other; p represents a number which may have the value 0, 1, 2 or 3; R3 represents a hydrogen or fluorine atom, a C1-6 alkyl group or a trifluoromethyl group; R4 represents a 5-membered heterocycle chosen from furanyl, pyrrolyl, thienyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, imidazolyl, triazolyl or tetrazolyl; this heterocycle optionally being substituted by one or more substituents selected from a halogen atom or a C1-6-alkyl, C1-6-haloalkyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-6 alkylene group, C1.6 -haloalkoxy, cyano, -NR 8 R 9, -NR 8 C (0) R 9, -NR 8 CO 2 R 9, -NR 8 SO 2 R 9, -NR 8 SO 2 N R 8 R 9, -C (0) R 8j -C 2 R 8i -C (0) NR 8 R 9j -C (0) N (R 8) (Ci- 3-alkylene-NR 10 R 11), -SO 2 R 8, -SO 2 NR 8 R 9 or -0- (C 1-3 alkylene) -0-; R8 and Rg independently representing a hydrogen atom or a C1-6 alkyl group, or forming with the nitrogen atom or atoms which carry them, in the case of NR8Rg, a ring chosen from the azetidine, pyrrole rings -lidine, piperidine, morpholine, thiomorpholine, azepine, oxazepine or piperazine, this ring being optionally substituted by a C1-6 alkyl or benzyl group; in the case of NR8CORg, a lactam ring; in the case of NR 8 CO 2 R 9, an oxazolidinone, oxazinone or oxazepinone ring; in the case of NR8S02Rg, a sultam ring; in the case of NR8 SO2 NR8 R9, a thiazolidine dioxide or thiadiazinane dioxide ring; R10 and R11 independently of one another represent a hydrogen atom or a C1-6 alkyl group; excluding the following compound: 5-methylisoxazol-3-ylmethyl 4-hydroxy-4- (4-chlorophenyl) -1-piperidine-1-carboxylate.

Among the compounds of general formula (I), a first subgroup of compounds is composed of compounds for which R2 represents a hydrogen atom.

Among the compounds of general formula (I), a second subgroup of compounds is composed of compounds for which m and n independently represent 1 or 2.

Among the compounds of general formula (I), a third subgroup of compounds is composed of compounds for which m and n each represent the value 2.

Among the compounds of general formula (I), a fourth subgroup of compounds are those compounds for which A represents a -0-C1-6 alkylene group in which the end represented by an oxygen atom is attached to the group R1, in particular a group -0- (CH2) 2-, also known as an ethyleneoxy group.

Among the compounds of general formula (I), a fifth subgroup of compounds are those compounds for which A represents an -O-C1- and alkylene group wherein the end represented by an oxygen atom is attached to the group R1, in particular a -O-CH 2 - group, also known as a methyleneoxy group.

Among the compounds of general formula (I), a sixth subgroup of compounds is composed of compounds for which R1 represents a group R5 optionally substituted by one or more groups Re and / or R7; R5 representing a chosen group of phenyl, pyridinyl, pyridinyl, pyrimidinyl, pyrazinyl, triazinyl, naphthyl, quinolinyl, isoquinolinyl, phthalazinyl, quinoxalinyl, quinazolinyl, cinolinyl, naphthyridinyl, benzothiazolyl, benzoxazol, benzoxazol isobenzofuranyl, benzofuranyl, benzothiophenyl, indazolyl, indolizinyl, indolyl, isoindolyl, pyrro-lopyridinyl, furopyridinyl or thienopyridinyl; R 6 representing a halogen atom or a cyano group, -CH 2 CN, nitro, hydroxyl, C 1-8 alkyl, C 1-6 alkoxy, C 1-6 thioalkyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 1-6 6-halothioalkyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-3 alkylene, C3-7-cycloalkyl-C1-3 alkyl [eno-O-, - (CH2) P-NR8 R9, -NRsCORg, -NR8 CO2 R9 , -NR 8 SO 2 R 9, -NR 8 SO 2 NR 8 R g, -COR 8, -C 2 R 8i - (CH 2) p -CONR 8 R 9, -SO 2 R 8, -SO 2 NR 8 R 9 or -0- (C 1-3 alkylene) -0-; R 7 represents a group selected from phenyl, phenyl-C 1-4 alkylene-, phenyl- (CH 2) p -0-, pyridinyl, pyridazinyl, isoxazolyl, benzothiazolyl, pyrrolyl, pyrazolyl, tetrazolyl, pyrimidinyl, thiazolyl, pyrazinyl, triazinyl or benzoxazolyl; being possible for the group or groups R7 to be substituted by one or more groups R6 which are identical to or different from each other as defined above; p represents a number which may have the value 0, 1, 2 or 3;

R5 and R5 independently of one another represent a hydrogen atom or a C1-6 alkyl group; or forming, with the nitrogen atom (s) carrying them, in the case of NR8Rg, a ring chosen from the rings azetidine, pyrrolidine, piperidine, morpholine, thiomorpholine, azepine, oxazepine or piperazine, this ring optionally being substituted by a C1-6 alkyl or benzyl group; in the case of NR8COR9, a lactam ring; in the case of NR 8 CO 2 R 9, an oxazolidinone, oxazinone or oxazepinone ring; in the case of NR8S02R9, a ring results; in the case of NR8 SO2 NR8 R9, a thiazolidine dioxide or thiadiazinane dioxide ring.

Among the compounds of general formula (I), a seventh subgroup of compounds is comprised of compounds for which R1 represents an Rg group optionally substituted by one or more R8 and / or R7 groups; R5 represents a group selected from phenyl, benzothiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, naphthyl, quinolinyl, iso-quinolinyl, phthalazinyl, quinoxalinyl, cinolinyl, naphthyridinyl or indolyl; R 6 representing a halogen atom or a cyano group, -CH 2 CN, nitro, hydroxyl, C 1-8 alkyl, C 1-6 alkoxy, C 1-6 thioalkyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 1-6 halothioalkyl, C3.7-cycloalkyl, C3.7-cycloalkyl-C1-3-alkylene, C3-7-cycloalkyl-C1-3-alkylene-0-, - (CH2) P-NR8R9, -NR8CORg, -NR8CO2R9, -NR8SO2Rg -COR8, -0O2R8, - (CH2) p -CONR8R9, -SO2 R8, -SO2 NR8 R9 or -0- (C1-3 alkylene) -0-; R7 representing a group selected from phenyl, phenyl-C1-4-alkylene-, phenyl- (CH2) p-0-, pyridinyl, pyridazinyl, isoxazolyl, benzothiazolyl, pyrrolyl, pyrazolyl, tetrazolyl, pyrimidinyl, thiazolyl, pyrazinyl, triazinyl or benzoxazolyl ; being possible for the group or groups R7 to be substituted by one or more groups R6 which are identical to or different from each other; p represents a number which may have the value 0, 1, 2 or 3; R8 and Rg independently representing a hydrogen atom or a C1-6 alkyl group, or forming, with the nitrogen atom which carries them, in the case of NRsR9, a ring chosen from the azetidine, pyrrho- lidine, piperidine, morpholine, thiomorpholine, azepine, oxazepine or piperazine, this ring being optionally substituted by a C1-6 alkyl or benzyl group; in the case of NRaCORg, a lactam ring; in the case of NR 8 CO 2 R 9, an oxazolidinone, oxazinone or oxazepinone ring; in the case of NR8S02R9, a ring results; in the case of NRsSC4 NRgRg, a thiazolidine dioxide or thiadiazinane dioxide ring.

Among the compounds of formula (I), an eighth subgroup of compounds are those compounds for which R1 represents a group selected from phenyl, benzothiazolyl, naphthyl, quinolinyl, isoquinolinyl or indolyl, optionally substituted by one or more groups Re and / or R7;

Re represents a halogen atom or a cyano, C 1-8 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 3-7 cycloalkyl, - (CH 2) p -NR 8 R 9, -NR 8 COR 9 1 -C 2 R 8, - (CH 2) p -CONR 8 R 9, -SO 2 R 8 or -SO 2 NR 8 R g; R7 represents a group selected from phenyl, phenyl-C1-4-alkylene-, phenyl- (CH2) p-O-, isoxazolyl, benzothiazolyl, pyrrolyl, pyrazolyl, te-bringolyl, thiazolyl or benzoxazolyl; being possible for the group or groups R7 to be substituted by one or more groups R6 which are identical to or different from each other as defined above; p represents a number that can have the value 0 or 1;

R5 and R9 independently of one another represent a hydrogen atom or a C1-6 alkyl group; or R8 and R9 forming, with the nitrogen atom carrying them, in the case of -NR8 Rg, a morpholine ring; in the case of -NR8CORg, a lactam ring.

Among the compounds of general formula (I), a ninth subgroup of compounds is composed of the compounds for which R3 represents a hydrogen atom.

Among the compounds of general formula (I), a tenth subgroup of compounds are those compounds for which R4 represents a 5-membered heterocycle chosen from pyrazolyl, imidazolyl, thiazolyl, isothiazolyl, oxazole or isoxazolyl; this heterocycle is optionally substituted by one or more -C (O) NR 8 R 6 substituents wherein R 8 and R 8 each represent a hydrogen atom.

Among the compounds of general formula (I), an eleventh subgroup of compounds are those compounds for which R4 represents a 5-membered heterocycle chosen from thiazolyl or isoxazolyl; this heterocycle is optionally substituted by one or more substituents of -C (O) NR 8 R 9 wherein R 8 and R 6 each represent a hydrogen atom.

Among the compounds of general formula (I), mention may be made of a twelfth subgroup represented by the compounds of formula (II): wherein R 1, R 4, n and m are as defined above.

Other compound subgroups of the compounds of formula (II) also come into the present invention.

Thus, among the compounds of formula (li) above, a subgroup of compounds is composed of the compounds for which A represents a group -0- (CH2) 2- · Among the compounds of formula (li) above A subgroup of compounds is composed of compounds for which A represents a group -O-CH 2 -.

Among the compounds of the general formula (I), mention may be made of a thirteenth subgroup represented by the compounds of the formula (III): wherein R1, A are not even as defined above.

Other subgroups consisting of the compounds of formula (III) also come into the present invention.

Thus, among the compounds of formula (lii) mentioned above, a subgroup of compounds is comprised of compounds for which A represents a group -0- (CH 2) 2 -.

Thus, among the compounds of formula (lii) mentioned above, a subgroup of compounds is composed of compounds for which A represents a group -0-CH 2 -.

Among the compounds of the general formula (I), a fourteenth subgroup consists of the compounds of the general formula (I) wherein: R2 represents a hydrogen atom; m and n independently represent 1 or 2; A represents a -O-C 1-6 alkylene group in which the end represented by an oxygen atom is attached to the R-η group, in particular an ethyleneoxy or methyleneoxy group; R 1 represents a group selected from phenyl, benzothiazolyl, naphthyl, quinolinyl, isoquinolinyl or indolyl, optionally substituted by one or more R 6 and / or R 7 groups; R 6 representing: - a halogen atom, in particular a chlorine, fluorine or bromine; - a cyan group; a C1-6 alkyl group, in particular methyl, isopropyl, 1,1,3,3-tetramethylbutyl or tert-butyl; a C1-6 alkoxy group, in particular methoxy, hexyloxy, butoxy, ethoxy; a C1-6 haloalkyl group, in particular trifluoromethyl, pentafluoroethyl; a C1-6 haloalkoxy group, in particular trifluoromethoxy or difluoromethoxy; a C 3-7 cycloalkyl group, in particular cyclopentyl; - - (CH2) p-NR8 R9, where p is 0 or 1; Rs and Rg each represent a hydrogen atom or Rs and Rg each represent methyl, or Rs and Rg form, with the nitrogen atom carrying them, a morpholine ring; - a group -NRsCORg, wherein Rs represents a hydrogen atom and Rg represents methyl, or Rs and Rg form, with the nitrogen atom carrying them, a lactam ring, in particular a β-lactam ring; - a group -CO 2 R 8. wherein Rs represents methyl; - (CH 2) p -CONR 8 R 9, wherein p is 0 or 1 and R 8 and R 8 each represent a hydrogen atom; - a group -SO 2 R 8, wherein R 8 represents methyl; - a group -SO2 NR8 R9, wherein R8 and R6 each represent a hydrogen atom; R7 represents a group selected from a phenyl group; a phenyl-C 1-4 alkylene- group, in particular 1,1-dimethyl-1-phenylmethylene or benzyl; a phenyl- (CH 2) p -O- group wherein p has a value of 0 or 1; or an isoxazolyl, benzothiazolyl, pyrrolyl, pyrazolyl, tetrazolyl, thiazolyl or benzoxazole group; being possible for the group or groups R 7 to be substituted by one or more groups R 6 which are identical to or different from each other as defined above such as a halogen atom or a cyano group; R3 represents a hydrogen atom; R4 represents a 5 membered heterocycle chosen from thiazolyl or isoxazolyl; this heterocycle is optionally substituted by one or more substituents of -C (O) NR 8 R 9 wherein R 8 and R 9 each represent a hydrogen atom.

Among the compounds of the general formula (I), a fifteenth subgroup of compounds consists of the compounds of the general formula (I) wherein simultaneously R 1 and / or R 2 and / or R 3 and / or R 4 and / or n and / or me and / or A are as defined in the above subgroups.

Among the compounds of general formula (I), the following compounds may be cited (IUPAC nomenclature generated by AutoNom software): 1. thi 4- [2- (4-chioronaph-1-yloxy) ethyl] piperidine-1-carboxylate -azol-2-ylmethyl 2. thiazol-2-ylmethyl 4- [2- (4-fluorophenoxy) ethyl] piperidine-1-carboxylate 3. 4- [2- (4-fluorophenoxy) ethyl] piperidine-1-carboxylate 4. thiazol-4-ylmethyl 4- [2- (4- {trifluoromethyl} phenoxy) ethyl] piperidine-1-carboxylate of thiazol-4-ylmethyl 5. 4- [2- (4-chlorophenoxy) ethyl] piperidine Thiazol-4-ylmethyl 1-carboxylate 6. thiazol-5-ylmethyl 4- [2- (4-fluorophenoxy) ethyl] piperidine-1-carboxylate 7. 4- [2- (4-chlorophenoxy) ethyl] piperidine-1 Thiazol-5-ylmethyl 1-carboxylate 8. 4- [2- (4- {trifluoromethyl} phenoxy) ethyl] piperidine-1-thiazol-5-ylmethyl 9-carboxylate 9. 4- [2- (7-methoxynaph-2 thiazol-4-ylmethyl-4-ylmethyl] -piperidine-1-carboxylate 10. thiazol-4-ylmethyl 4- [2- (4-cyanophenoxy) ethyl] -piperidine-1-carboxylate 11. (+/-) -3 - (6-methoxynaphth-2-yloxymethyl) pyrrolidine-1-carboxylate 12. (+/-) -3- (7-methoxynaphth-2-yloxymethyl) pyrrolidin-1-thiazol-4-ylmethyl 13. (+/-) -3- (3,4) thiazol-4-ylmethyl ester thiazol-4-ylmethyl-4- dichlorophenoxymethyl) pyrrolidin-1-carboxylate 14. thiazol-4-ylmethyl 4- [2- (6-methoxynaphth-2-yloxy) ethyl] piperidine-1-carboxylate 15. 4- [2- thiazol-4-ylmethyl (naphth-2-yloxy) ethyl] piperidine-1-carboxylate 16. (+/-) -3- (4-chloronaph-1-yloxymethyl) pyrrolidine-1-carboxylate of thiazol-4-ylmethyl 17. thiazol-4-ylmethyl (+/-) -3- (naphth-2-yloxymethyl) pyrrolidin-1-carboxylate 18. 4- [2- (4'-fluorobiphenyl-4-yloxy) ethyl] piperidine Thiazol-4-ylmethyl 1-carboxylate 19. thiazol-4-ylmethyl 4- [2- (quinolin-6-yloxy) ethyl] piperidine-1-carboxylate and its hydrochloride 20. 4- [2- ( thiazol-4-ylmethyl isoquinolin-6-yloxy) ethyl] piperidine-1-carboxylate and its hydrochloride 21. (+/-) -3- (3'-cyanobiphenyl-3-yloxymethyl) pyrrolidine-1-carboxylate thiazol-4-ylmethyl 22. (+/-) -3- (4'-fluorobiphenyl-4-yloxymethyl) pyrrolidin-1-thiazol-4-ylmethyl 23. (+/-) -3- (5-chloron) thiazol-4-ylmethyl aft-2-yloxymethyl) pyrrolidin-1-carboxylate 24. (+/-) -3- (3- {trifluoromethoxy} phenoxymethyl) pyrrolidine-1-carboxylate 25. (+ / -) - Thiazol-4-ylmethyl 3- [4- (1-methyl-1-phenylethyl) phenoxymethyl] pyrrolidine-1-carboxylate 26. (+/-) -3- (quinolin-3-yloxymethyl) pyrrolidine-1 Thiazol-4-ylmethyl 1-carboxylate 27. (+/-) -3- (isoquinolin-6-yloxymethyl) pyrrolidine-1-thiazol-4-ylmethyl 1-carboxylate 28. (+/-) -3- (quinolinyl) Thiazol-4-ylmethyl 7-yloxymethyl) pyrrolidin-1-carboxylate 29. (+/-) -3- (isoquinolin-7-yloxymethyl) thiazol-4-ylmethyl 3- (isoquinolin-7-yloxymethyl) -pyrrolidine-1-carboxylate 30. (+/-) Thiazol-4-ylmethyl -3- (4-chloro-3- {trifluoromethyl} phenoxymethyl) pyrrolidine-1-carboxylate 31. (+/-) -3- (5-fluoronaph-2-yloxymethyl) pyrrolidine-1-carboxylate thiazol-4-ylmethyl 32. 4- [2- (2,4-dimethylphenoxy) ethyl] piperidine-1-carboxylate of thiazol-2-ylmethyl 33. 4- [2- (2,3-dichlorophenoxy) ethyl ] thiazol-2-ylmethyl piperidine-1-carboxylate 34. thiazol-2-ylmethyl 4- [2- (2,4-dichlorophenoxy) ethyl] piperidine-1-carboxylate zol-2-ylmethyl 35. thia-ζοΙ-2-ylmethyl 4- [2- (2,5-dichlorophenoxy) ethyl] piperidine-1-carboxylate 36. 4- [2- (3,4-dichlorophenoxy) ethyl] thiazol-2-ylmethyl piperidine-1-carboxylate 37. thiazol-2-ylmethyl 4- [2- (3,5-dichlorophenoxy) ethyl] piperidine-1-carboxylate 38. 4- [2- ( Thiazol-2-ylmethyl 4-cyclopentylphenoxy) ethyl] piperidine-1-carboxylate 39. thiazole-2-4- [2- (2- {benzoxazoyl-2-yl} phenoxy) ethyl] piperidine-1-carboxylate ylmethyl 40. thiazol-2-ylmethyl 4- [2- (4- {benzyloxy} phenoxy) ethyl] piperidine-1-carboxylate 41. 4- [2- (4- {carbamoylmethyl} phenoxy) ethyl] piperidine-1- thiazol-2-ylmethyl carboxylate 42. thiazol-2-ylmethyl 4- [2- (quinolin-7-yloxy) ethyl] piperidine-1-carboxylate and its trifluoroacetate 43. 4- [2- (quinolin-6 thiazol-2-ylmethyl-3-piperidine-1-carboxylate and its trifluoroacetate 44. Thiazol-2-ylmethyl 4- [2- (4-cyano-3-fluorophenoxy) ethyl] piperidine-1-carboxylate 45. Thiazoyl-2-ylmethyl 4- [2- (biphenyl-2-yloxy) ethyl] piperidine-1-carboxylate 46. 4- [2- (2-isopropyl) thiazol-2-ylmethyl 1-5-methylphenoxy) ethyl] piperidine-1-carboxylate 47. thiazol-2-ylmethyl 4- [2- (3- {trifluoromethyl} phenoxy) ethyl] piperidine-1-carboxylate 48. 4 - thiazol-2-ylmethyl {2- [4- (1,1,3,3-tetramethylbutyl) phenoxy] ethyl} piperidine-1-carboxylate 49. 4- [2- (4-benzylphenoxy) ethyl] piperidine-1 thiazol-2-ylmethyl-carboxylate 50. thiazol-2-ylmethyl 4- [2- (4- {pyrrol-1-yl} phenoxy) ethyl] piperidine-1-carboxylate and its trifluoroacetate 51. 4- [2 - (4-carbamoylphenoxy) ethyl] piperidine-1-carboxylate and thiazol-2-ylmethyl 52. thiazol-2-ylmethyl 4- [2- (3-cyanophenoxy) ethyl] piperidine-1-carboxylate 53. 4- Thiazol-2-ylmethyl [2- (3,5-di {tert-butyl} phenoxy) ethyl] piperidine-1-carboxylate 54. thiazole 4- [2- (2-benzylphenoxy) ethyl] piperidine-1-carboxylate - 2-ylmethyl 55. thiazol-2-ylmethyl 4- [2- (8- {acetylamino} naphth-2-yloxy) ethyl] piperidin-1-carboxylate 56. 4- [2- (3- {methoxycarbonyl} naphtho Thiazol-2-ylmethyl 2-yloxy) ethyl] piperidine-1-carboxylate 57. 4- [2- (3-phenoxyphenoxy) ethyl] piperidine-1-carboxylate thiazol-2-ylmethyl 58. 4- [2- (isoquinolin-7-yloxy) ethyl] piperidine-1-carboxylate of thiazol-2-ylmethyl and its trifluoroacetate 59. 4- [2- (4-hexyloxyphenoxy thiazol-2-ylmethyl ethyl] piperidine-1-carboxylate 60. thiazol-2-ylmethyl 4- [2- (3-butoxyphenoxy) ethyl] piperidine-1-carboxylate 61. 4- [2- (quinolin Thiazol-2-ylmethyl-5-yloxy) ethyl] piperidine-1-carboxylate and its trifluoroacetate 62. 4- [2- (3- {pentafluoroethyl} phenoxy) ethyl] piperidine-1-carboxylate -ylmethyl 63. thiazol-2-ylmethyl 4- [2- (5- {acetylamino} naphth-2-yloxy) ethyl] piperidine-1-carboxylate 64. 4- [2- (5-bromo-2-chlorophenoxy) ethyl] thiazol-2-ylmethyl piperidine-1-carboxylate 65. thiazol-2-ylmethyl 4- [2- (2-methylquinolin-6-yloxy) ethyl] piperidine-1-carboxylate and its trifluoroacetate 66. 4- [ Thiazol-2-ylmethyl 2- (4'-cyanobiphenyl-3-yloxy) ethyl] piperidine-1-carboxylate 67. thiol 4- [2- (6-cyanonaphth-2-yloxy) ethyl] piperidine-1-carboxylate -azol-2-ylmethyl 68. 4- [2- (4- {thiazol-2-yl} phenoxy) ethyl] piperidine-1-carboxylate thiazol-2-ylmethyl 69. thiazol-2-ylmethyl 4- [2- (biphenyl-3-yloxy) ethyl] piperidine-1-carboxylate 70. 4- [2- (biphenyl-4-yloxy) ethyl] piperidine Thiazol-2-ylmethyl 1-carboxylate 71. thiazol-2-ylmethyl 4- [2- (2-cyanoquinolin-8-yloxy) ethyl] piperidine-1-carboxylate and its trifluoroacetate 72. 4- [2- (4 thiazol-2-ylmethyl-piperidine-1-carboxylate thiazol-2-ylmethyl-trifluoroacetate and its trifluoroacetate 73. thiazol-2 4- [2- (2-methylbenzothiazol-5-yloxy) ethyl] -piperidine-1-carboxylate -ylmethyl 74. thiazol-2-ylmethyl 4- [2- (4'-cyanobiphenyl-4-yloxy) ethyl] piperidine-1-carboxylate 75. 4- [2- (2- {morpholin-4-yl} phenoxy thiazol-2-ylmethyl] ethyl] piperidin-1-carboxylate 76. thiazol-2-ylmethyl 4- [2- (4-chloro-2- {isoxazol-5-yl} phenoxy) ethyl] piperidin-1-carboxylate 77. thiazol-4-ifmethyl 4- [2- (2,4-dimethylphenoxy) ethyl] piperidine-1-carboxylate 78. 4- [2- (2,3-dichlorophenoxy) ethyl] piperidine-1-carboxylate thiazol-4-ylmethyl ester 79. thiazol-4-ylmethyl 4- [2- (naphth-1-yloxy) ethyl] piperidine-1-carboxylate 80. 4- [2- (3- thiazol-4-ylmethyl {dimethylamino} phenoxy) ethyl] piperidine-1-carboxylate and its trifluoroacetate 81. thiazol-4-ylmethyl 4- [2- (3- {trifluoromethyl} phenoxy) ethyl] piperidine-1-carboxylate 82 Thiazol-4-ylmethyl 4- [2- (4-benzylphenoxy) ethyl] piperidine-1-carboxylate 83. thiazol-4-ylmethyl 4- [2- (2-ethoxyphenoxy) ethyl] piperidine-1-carboxylate 84 Thiazol-4-ylmethyl 4- {2- [4- (1-methyl-1-phenylethyl) phenoxy] ethyl} piperidine-1-carboxylate 85. 4- [2- (4-phenoxyphenoxy) ethyl] piperidine-1 thiazol-4-ylmethyl-carboxylate 86. 4- [2- (2-bromo-4-fluorophenoxy) ethyl] piperidine-1-thiazol-4-ylmethyl carboxylate 87. 4- [2- (2-benzylphenoxy) ethyl ] thiazol-4-ylmethyl piperidine-1-carboxylate 88. thiazol-4-ylmethyl 4- [2- (3-phenoxyphenoxy) ethyl] piperidine-1-carboxylate 89. 4- [2- (4- {hexyloxy} thiazol-4-ylmethyl phenoxy) ethyl] piperidine-1-carboxylate 90. thiazol-4-ylmethyl 4- [2- (3-butoxyphenoxy) ethyl] piperidine-1-carboxylate 91. 4- [2- ( Thiazoi-4 4-chloro-5-isopropyl-2-methylphenoxy) ethyl] piperidine-1-carboxylate 92. 4- [2- (5- {acetylamino} naphthyl] -ethylmethyl 92. thiazol-4-ylmethyl 4- [2- (3- {pentafluoroethyl} phenoxy) ethyl] piperidin-1-carboxylate 93. Thiazol-4-ylmethyl 2-yloxy) ethyl] piperidin-1-carboxylate 94. thiazol-4-ylmethyl 4- [2- (5-bromo-2-chlorophenoxy) ethyl] piperidine-1-carboxylate 95. 4- Thiazol-4-ylmethyl [2- (4'-cyanobiphenyl-3-yloxy) ethyl] piperidine-1-carboxylate 96. 4- [2- (6-cyanonaphth-2-yloxy) ethyl] piperidine-1-carboxylate thiazol-4-ylmethyl 97. thiazol-4-ylmethyl 4- [2- (4- {thiazol-2-yl} phenoxy) ethyl] piperidin-1-carboxylate 98. 4- [2- (biphenyl-3 thiazol-4-ylmethyl-4-ylmethyl-piperidine-1-carboxylate 99. thiazol-4-ylmethyl-4- [2- (biphenyl-4-yloxy) ethyl] -piperidin-1-carboxylate 100. 4- [2- Thiazol-4-ylmethyl (4-chloro-2-cyanophenoxy) ethyl] piperidine-1-carboxylate 101. thiazol-4-4- [2- (2-methylbenzothiazol-5-yloxy) ethyl] piperidine-1-carboxylate ylmethyl 102. thiazol-4-ylmethyl 4- [2- (4'-cyanobiphenyl-4-yloxy) ethyl] piperidine-1-carboxylate 103. 4- [2- (2- {morpholin-4-ii} phenoxy) ethyl] thiazol-4-ylmethyl piperidin-1-carboxylate and its trifluoroacetate 104. thiazol-4-ylmethyl 4- [2- (4-chloro-2- {isoxazol-5-yl} phenoxy) ethyl] piperidine-1-carboxylate 105. Thiazol-2-ylmethyl 4- [2- (4- {dimethylaminomethyl} phenoxy) ethyl] piperidine-1-carboxylate and its trifluoroacetate 106. 4- [2- (naphth-2-yloxy) ethyl] piperidine-1 -thiazol-2-ylmethyl-carboxylate 107. thiazol-2-ylmethyl 4- [2- (naphth-1-yloxy) ethyl] piperidine-1-carboxylate 108. 4- [2- (7-methoxynaphth-2-yloxy thiazol-2-ylmethyl ethyl] piperidine-1-carboxylate 109. thiazol-4-ylmethyl 4- [2- (2-cyclopentylphenoxy) ethyl] piperidine-1-carboxylate 110. 4- [2- (2 thiazol-4-ylmethyl-piperidine-1-carboxylate thiazol-4-ylmethyl 111.-thiazol-4-ylmethyl 4- [2- (isoquinolin-7-yloxy) ethyl] piperidine-1-carboxylate and its trifluoroacetate 112. thiazol-4-ylmethyl 4- [2- (quinolin-5-yloxy) ethyl] piperidine-1-carboxylate and its trifluoroacetate 113. 4- [2- (2-methylquinolin-6-yloxy) ethyl] thiazol-4-ylmethyl piperidine-1-carboxylate and its trifluoroace tate 114. Thiazol-4-ylmethyl 4- [2- (2-cyanoquinolin-8-yloxy) ethyl] piperidine-1-carboxylate and its trifluoroacetate 115. 4- [2- (2,4-dichlorophenoxy) ethyl] piperidine Thiazol-4-ylmethyl -1-carboxylate 116. 4- [2- (4-cyclopentylphenoxy) ethyl] piperidine-1-carboxy [thiazol-4-ylmethyl actin 117. 4- [2- (2 - thiazol-4-ylmethyl {benzoxazol-2-yl} phenoxy) ethyl] piperidine-1-carboxylate 118. thiazol-4 4- [2- (4-cyano-3-fluorophenoxy) ethyl] piperidine-1-carboxylate -ylmethyl 119. thiazol-4-ylmethyl 4- {2- [4- (1,1,3,3-tetramethylbutyl) phenoxy] ethyl} piperidine-1-carboxylate 120. 4- [2- (4- {pyrrole Thiazol-4-ylmethyl -1-yl} phenoxy) ethyl] piperidine-1-carboxylate and its trifluoroacetate 121. 4- [2- (3,5-di {tert-butyl} phenoxy) ethyl] piperidine-1-carboxylate -thiazol-4-ylmethyl 122. 4- [2- (4- {dimethylaminomethyl} phenoxy) ethyl] piperidine-1-carboxylate of thiazol-4-ylmethyl and its trifluoroacetate 123. 4- [2- (2-methylquinolin-8 thiazol-4-ylmethyl-piperidine-1-carboxylate and its trifluoroacetate 124. 4- [2- (3-cyanophenoxy) ethyl] thiazol-4-ylmethyl piperidine-1-carboxylate 125. thiazol-5-ylmethyl 4- (2-phenoxyethyl) piperidine-1-carboxylate 126. 4- [2- (biphenyl-4-yloxy) ethyl] piperidine Thiazol-5-ylmethyl -1-carboxylate 127. thiazol-5-ylmethyl 4- [2- (4-carbamoylphenoxy) ethyl] piperidine-1-carboxylate 128. 4- [2- (4-fluorophenoxy) ethyl ] thiazol-5-ylmethyl piperidine-1-carboxylate 129. thiazol-5-ylmethyl 4- [2- (2,4-dimethylphenoxy) ethyl] piperidine-1-carboxylate 130. 4- [2- (4 - thiazol-5-ylmethyl {dimethylaminomethyl} phenoxy) ethyl] piperidine-1-carboxylate and its trifluoroacetate 131. thiazol-5-4- [2- (2,3-dichlorophenoxy) ethyl] piperidine-1-carboxylate ylmethyl 132. thiazol-5-ylmethyl 4- [2- (2,4-dichlorophenoxy) ethyl] piperidine-1-carboxylate 133. 4- [2- (2,5-dichlorophenoxy) ethyl] piperidine-1-one thiazol-5-ylmethyl carboxylate 134. 4- [2- (3,5-dichlorophenoxy) ethyl] piperidine-1-thiazol-5-ylmethyl carboxylate 135. 4- [2- (4-cyclopentylphenoxy) thiazol-5-ylmethyl ethyl] piperidine-1-carboxylate 136. 4- [2- (naphth-2-yloxy) et thiazol-5-ylmethyl yl piperidine-1-carboxylate 137. thiazol-5-ylmethyl 4- [2- (naphth-1-yloxy) ethyl] piperidine-1-carboxylate 138. 4- [2- (2- thiazol-5-ylmethyl methylquinolin-8-yloxy) ethyl] piperidine-1-carboxylate 139. thiazol-5-4- [2- (2- {benzoxazol-2-yl} phenoxy) ethyl] piperidine-1-carboxylate ylmethyl 140. thiazol-5-ylmethyl 4- [2- (4- {benzyloxy} phenoxy) ethyl] piperidine-1-carboxylate 141. thiol 4- [2- (4-sulfamoylphenoxy) ethyl] piperidine-1-carboxylate azol-5-ylmethyl 142. 4- [2- (isoquinolin-5-yloxy) ethyl] piperidine-1-carboxylate of thiazol-5-ylmethyl 143. 4- [2- (4- {carbamoylmethyl} phenoxy) thiazol-5-ylmethyl ethyl] piperidine-1-carboxylate 144. thiazol-5-ylmethyl 4- [2- (quinolin-7-yloxy) ethyl] piperidine-1-carboxylate 145. 4- [2- ( thiazol-5-ylmethyl quinoline-6-yloxy) ethyl [] piperidine-1-carboxylate 146. thiazol-5-4- [2- (quinolin-8-yloxy) ethyl] piperidine-1-carboxylate ylmethyl 147. thiazol-5-ylmethyl 4- [2- (3- {dimethylamino} phenoxy) ethyl] piperidine-1-carboxylate and its trifluoroacetate 148. Thiazol-5-ylmethyl 4- [2- (4-cyano-3-fluorophenoxy) ethyl] piperidine-1-carboxylate 149. 4- [2- (biphenyl-2-yloxy) ethyl] piperidine-1-carboxylate 150. 4- [2- (Biphenyl-3-yloxy) ethyl] piperidine-1-carboxylate of thiazol-5-ifmethyl 151. 4- [2- (3- {trifluoromethyl} phenoxy) ethyl] thiazol-5-ylmethyl piperidin-1-carboxylate 152. [4- (2- (2-ethoxyphenoxy) ethyl]] 4- [2- (4-benzylphenoxy) ethyl] thiazol-5-ylmethyl piperidine-1-carboxylate 153. 4- [2- (2-ethoxyphenoxy) ethyl] thiazol-5-ylmethyl piperidine-1-carboxylate 154. thiazol-5-ylmethyl 4- [2- (2-cyclopentylphenoxy) ethyl] piperidine-1-carboxylate 155. 4- {2- [4- (1 thiazol-5-ylmethyl-1-phenylethyl-phenoxy] -ethyl} -piperidine-1-carboxylate 156. thiazol-5-methyl-4- [2- (4-phenoxyphenoxy) ethyl] -piperidine-1-carboxylate 157. 4 - thiazol-5-methyl-methyl [1- (2-bromo-4-fluorophenoxy) ethyl] piperidine-1-carboxylate 158. 4- [2- (4- {pyrrol-1-yl} phenoxy) ethyl] piperidine Thiazol-5-ylmethyl 1-carboxylate 159. thiazol-5-4- 4- (2- (3-cyanophenoxy) ethyl] piperidine-1-carboxylate methyl 160. 4- (2- (3,5-di {tert-butyl} phenoxy) ethyl] piperidine-1-thiazol-5-ylmethyl 161. 4- [2- (2-benzylphenoxy) ethyl] piperidine-1-one Thiazol-5-ylmethyl 1-carboxylate 162. 4- (2- (2- {benzyloxy} phenoxy) ethyl] piperidine-1-thiazol-5-ylmethyl 1-carboxylate 163. 4- (2- (2-cyanoquinolin-8 thiazol-5-ylmethyl 4-ylmethyl] piperidine-1-carboxylate 164. thiazol-5-ylmethyl 4- [2- (3- {methoxycarbonyl} naphth-2-yloxy) ethyl] piperidine-1-carboxylate 165. Thiazol-5-4- [2- (3-phenoxyphenoxy) ethyl] piperidine-1-carboxylate 166. thiazol-5 4- [2- (4-chloro-2-cyanophenoxy) ethyl] piperidine-1-carboxylate 167. 4- [2- (4- (Hexyloxy} phenoxy) ethyl] piperidine-4-ylmethyl] piperidine-4-yl [2- (isoquinolin-7-yloxy) ethyl] piperidine-1-carboxylate Thiazol-5-ylmethyl 1-carboxylate 169. thiazol-5-ylmethyl 4- [2- (3-butoxyphenoxy) ethyl] piperidine-1-carboxylate 170. 4- [2- (4-chloro-5- thiazol-5-ylmethyl isopropyl-2-methylphenoxy) ethyl] piperidine-1-carboxylate 171. 4- [2- (2-methylbenzothiazol-5-yloxy) ethyl] piperid thiazol-5-ylmethyl-1-carboxylate 172. 4- thiazol-5-ylmethyl 4- [2- (quinolin-5-yloxy) ethyl] piperidine-1-carboxylate 173. 4- [2- (3- thiazol-5-ylmethyl {pentafluoroethyl} phenoxy) ethyl] piperidine-1-carboxylate 174. thiazol-5-ylmethyl 4- [2- (5-bromo-2-chlorophenoxy) ethyl] piperidine-1-carboxylate 175. 4 - thiazol-5-ylmethyl [1- (4- {difluoromethoxy} phenoxy) ethyl] piperidine-1-carboxylate 176. 4- {2- (4'-cyanobiphenyl-3-yloxy) ethyl] piperidine-1-carboxylate thiazol-5-ylmethyl 177. 4- [2- (6-cyanonaphth-2-yloxy) ethyl] piperidine-1-carboxylate thiazol-5-ylmethyl 178. 4- [2- (4- {thiazol-2 thiazol-5-ylmethyl-1-phenyloxy-ethyl-piperidine-1-carboxylate 179. thiazol-5-ylmethyl 4- [2- (7-methoxynaphth-2-yloxy) ethyl] -piperidine-1-carboxylate 180.4 - thiazol-5-ylmethyl [2- (4-chloro-2- {isoxazol-5-yl} phenoxy) ethyl] pipendin-1-carboxylate 181. 4- [2- (2-carbamoyl-4-chlorophenoxy) ethyl ] thiazol-5-ylmethyl piperidine-1-carboxylate 182. 4-1,2- (5- {acetylamino} naphth-2-yloxy) ethyl] thiazol-5-ylmethyl piperidine-1-carboxylate 183. thiazol-5-ylmethyl 4- [2- (4'-cyanobiphenyl-4-yloxy) ethyl] piperidine-1-carboxylate 184. 4- [2- (4- {methanesulfonyl} phenoxy) ethyl] piperidine-1 -thiazol-5-ylmethyl-carboxylate 185. 4- [2- (5-acetylamino-2-propylphenoxy) ethyl] piperidine-1-thiazol-5-ylmethyl carboxylate 186. 4- [2- (1H-indol-6 thiazol-5-ylmethyl-1-yloxyethyl) piperidine-1-carboxylate 187. 4- {2- [4-fluoro-2- (1H-pyrazol-3-yl) phenoxy] ethyl} piperidine-1-one thiazol-5-ylmethyl carboxylate 188. 4- [2- (4-cyano-2-fluorophenoxy) ethyl] piperidine-1-thiazol-5-ylmethyl carboxylate 189. 4- [2- (2-isopropyl-5- thiazol-5-ylmethyl methylphenoxy) ethyl] piperidin-1-carboxylate 190. thiazol-5-ylmethyl 4- [2- (2- {morpholin-4-yl} phenoxy) ethyl] piperidine-1-carboxylate and its trifluoroacetate 191. Thiazol-5-ylmethyl 4- [2- (2-methylquinolin-6-yloxy) ethyl] piperidine-1-carboxylate 192. 4- {2- [4- (2-oxopyrrolidin-1-yl) phenoxy] thiazol-5-methylmethyl} piperidine-1-carboxylate 193. thiazole-5-4- [2- (3- {tetrazol-1-yl} phenoxy) ethyl] thiazol-5-piperidine-1-carboxylate ylmethyl 194. (R) -3- (naphth-2-yloxymethyl) pyrrolidine-1-thiazol-2-ylmethyl (enantiomer I) 195. (S) -3- (naphth-2-yloxymethyl) pyrrolidine-1- thiazol-2-ylmethyl carboxylate (enantiomer II) 196. (+/-) -3- (5-chloronaph-2-yloxymethyl) pyrrolidine-1-thiazol-2-ylmethyl carboxylate 197. (+/-) -3 - Thiazol-2-ylmethyl (4'-fluorobiphenyl-4-yloxymethyl) pyrrolidine-1-carboxylate 198. 3-Carbamoylisoxazol-5-ylmethyl 4- [2- (4-fluorophenoxy) ethyl] piperidine-1-carboxylate 3-Carbamoylisoxazol-5-ylmethyl 4- [2- (4- {trifluoromethoxy} phenoxy) ethyl] piperidine-1-carboxylate 200. (-) - (R) -3- (naphth-2-yloxymethyl) pyrrolidine- 3-carbamoylisoxazol-5-ylmethyl 3-carbamoylisoxazol-5-ylmethyl 1-carboxylate (enantiomer I) 201. (+/-) -3- (6-methoxynaphth-2-yloxymethyl) pyrrolidine-1-carboxylate 202. ( +) - 3-Carbamoylisoxazol-5-ylmethyl (enantiomer II) (S) -3- (naphth-2-yloxymethyl) pyrrolidine-1-carboxylate (enantiomer II).

The compounds of the general formulas (I), (II) and (III) may comprise one or more asymmetric carbon atoms. They may exist in the form of enantiomers or diastereoisomers. These enantiomers and diastereoisomers and mixtures thereof, including racemic mixtures, come into the invention.

The compounds of formulas (I), (II) and (III) may exist in the form of bases or acid addition salts. Such addition salts come into the invention.

These salts are advantageously prepared with pharmaceutically acceptable acids, but salts of other acids, for example for use in purifying or isolating the compounds of formulas (I), (II) and (III), also come into the invention.

The compounds of formulas (I), (II) and (III) and / or salts thereof may form solvates or hydrates and the invention includes all such solvates and hydrates.

The terms "hydrates" and "solvates" mean that the compounds of formulas (I), (li) and (lii) according to the invention may be combined or associated with one or more water or solvent molecules. This is just a chemical characteristic of such compounds, which can be applied to all organic compounds of this type.

In the context of the invention: - Ct-z, where complexions may take values from 1 to 8, is understood to mean a carbon-comprising chain which may have from all carbon atoms, for example C1-3 is understood to mean a carbon-comprising chain which may have carbon atoms. may have from 1 to 3 carbon atoms; alkyl is understood to mean a straight or branched and saturated aliphatic group; for example, a C 1-6 alkyl group represents a chain comprising straight or branched carbon of 1 to 6 carbon atoms, more particularly methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl or hexyl; alkylene is understood to mean a linear or branched and saturated divalent alkyl group; for example, a C 1-3 alkylene group represents a chain comprising straight or branched divalent carbon of 1 to 3 carbon atoms, more particularly methylene, ethylene, 1-methylethylene or propylene; cycloalkyl is understood to mean a cyclic alkyl group; for example, a C 3-7 cycloalkyl group represents a group comprising cyclic carbon of 3 to 7 carbon atoms, more particularly cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloeptyl; alkoxy is understood to mean an -O-alkyl group comprising a straight or branched and saturated aliphatic chain; -thioalkyl is understood to mean a -S-alkyl group comprising a straight or branched and saturated aliphatic chain; haloalkyl is understood to mean an alkyl group, one or more hydrogen atoms which have been replaced by a halogen atom; haloalkoxy is understood to mean an alkoxy group, one or more hydrogen atoms which have been replaced by a halogen atom; halothioalkyl is understood to mean a thioalkyl group, one or more hydrogen atoms which have been replaced by a halogen atom; halogen atom is understood to mean a fluorine, chlorine, bromine or iodine; TFA is understood to mean trifluoroacetic acid; ACN is understood to mean acetonitrile.

Within the meaning of the present invention, it should be noted that the terms "ranging from ... to ..." and "between ... and ..." mean that the limits are also considered. The term "prevention" as used herein means reducing the risk of onset or decreasing the occurrence of a particular phenomenon, that is, in the present invention, a condition in which endogenous cannabinoids and / or other substrates metabolised by the FAAH enzyme are involved. as the pathologies as defined below.

Another subject matter of the invention is targeted in a process for the preparation of the compounds of formula (I) according to the invention, comprising the stage of reaction of an amine derivative, a compound of the following general formula (II): ( II) wherein R 1, R 2, A, nor are as defined in formula (I) defined above, with a carbonate of the following general formula (III): wherein U represents a hydrogen atom or a nitro group and R 3 and R 4 are as defined in the general formula (I) defined above, in the presence of a base such as triethylamine, pyridine, N, N-dimethylaminopyridine or N, N-diisopropylethylamine in an organic solvent such as toluene. acetonitrile or dichloroethane at a temperature between room temperature and the refluxing temperature of the solvent.

In addition, the compounds of the invention may be prepared according to different methods illustrated by the following schemes. These methods and the intermediate compounds used are also a subject matter of the present invention.

If appropriate, a compound of formula (II) may be protected, particularly in its amine functional group, according to methods well known to one of ordinary skill in the art.

Mention may be made, as examples of protecting groups as well as methods of protection and deprotection, to the work "Protective Groups in Organic Synthesis", Green et al., 2nd Edition (John Wiley & Sons, Inc., New York).

A preparation process employing a protected compound of formula (II) is, for example, described in the following scheme 1.

Most particularly for compounds of general formula (I) wherein A more particularly represents an oxygen atom or a -O-C 1-6 alkylene group, they may also be prepared according to the procedure described in the following scheme 1.

This preparation method (Scheme 1) consists in the reaction, in a first step, of an alcohol of the general formula (IIa), wherein R2, m and m are as defined in the general formula (I) as defined above, G represents a portion of group A as defined in general formula (I), that is, a covalent bond or the C1-6 alkylene moiety of the -0-C1-6 alkylene group, and PG represents a protecting group such as a Boc (tert-butyloxycarbonyl), a Cbz (benzyloxycarbonyl), a benzyl or a benzhydryl; - with an alcohol derivative of the general formula (IV), wherein R 1 is as defined above using the Mitsunobu reaction conditions (Synthesis, 1981, 1-28), - or with a halogenated derivative of the general formula (IVa), wherein R1 is as defined above and X represents a fluorine, chlorine, bro-mo or iodine atom using aromatic or heoaromatic nucleophilic substitution reactions or Buchwald O-heteroarylation or O-arylation reactions, for example using a palladium or copper catalyst; followed by a deprotection reaction, for example in the presence of trifluoroacetic acid or a solution of hydrochloric acid in isopropanol or dioxane, to yield the amine of general formula (IIb) wherein G, R2 and m are as defined in the amine of formula (IIa) above and R1 is as defined in general formula (I) as defined above. An alternative to the Mitsunobu reaction is the reaction of an alcohol derivative of formula (IV) with a compound said to be of formula (Ile) and derivatization of the activation by an tosylate group of the alcohol functional group of a compound of formula ( lia). The derivative of formula (11b) thus obtained is subsequently converted to the compound of formula (I) according to a condensation reaction with a carbonate of formula (III) as defined above under the conditions described above.

An alternative way of producing the compounds of formula (I) (Scheme 1) wherein A more particularly represents an oxygen atom or a group -O-C1- and alkylene is by deprotection of an alcohol of formula (IIa). as defined above according to a deprotection reaction as defined above to obtain an amino alcohol of the general formula (llc), and then in the reaction of this amino alcohol of the general formula (llc) wherein R2, m and n are as defined in formula (I) defined above and G represents a portion of group A as defined in general formula (I), that is, a covalent bond or the C1-6 alkylene portion of the group -O-C1- and alkylene with a carbonate of the general formula (III) as defined above under the conditions described above to yield the carbamate derivative of the general formula (Ia) wherein R2, R3, R4, m and n are as defined in the general formula (I) defined above and G represents a portion of group A as defined in the general formula (I), that is, a covalent bond or the C1-6 alkylene moiety of the -O-C1-6 alkylene group. The carbamate derivative (Ia) thus obtained is subsequently converted to the compound of general formula (I) by the action of an alcohol of the general formula R-iOH (IV) as defined above using the Mitsunobu reaction conditions or by the action of a halogenated derivative of the general formula R1X (IVa) as defined above using aromatic or heteroaromatic nucleophilic substitution reactions or Buchwald O-heteroarylation or O-arylation reactions, for example using a palladium or copper catalyst.

More particularly those compounds of formula (I) wherein R 1 represents a group R 5 substituted in particular by a group R 6 of the C 1-6 alkyl, C 3-7 cycloalkyl or C 1-6 cycloalkyl-C 1-6 alkylene type or by a group R 7 as defined in the general formula (I) defined above, they may also be prepared according to the procedure described in the following scheme 2.

Suzuki or Stille or Hegishi (I) Thus, the first stage is the reaction of an amine of the general formula (lld), wherein A, R2, Rs, m and m are as defined in the general formula (I) defined above and Ui represents a chlorine, bromine or iodine atom or a triflate group having a carbonate of the general formula (III) as defined above under the conditions described above to yield the carbamate derivative of the general formula (Ib) wherein A R2, R3, R4, R6, m and m are as defined in the general formula (I) defined above and Ui is as defined above. The transition metal catalyzed coupling reaction such as palladium (O) is subsequently performed on the key intermediate of the general formula (Ib) as defined above, U1 being in the position where it is desired to introduce the group R6 or R7 (Scheme 2): - by a Suzuki-type reaction, for example using an alkyl-, cycloalkyl-, aryl- or heteroarylboronic acid, - or according to a Stille-type reaction, for example using a trialkylaryl tin derivative or trialkyleteroaryl tin, - or by a Negishi-type reaction, for example using an alkyl-, cycloalkyl-, aryl- or heteroarylzinc halide derivative.

Alternatively, the other compounds of the general formulas (II), (Ha), (11b), (11c), (11d), (III), (IV) and (IVa) and the other reagents are commercially available or described in They may be prepared in accordance with the methods described herein or known to one of ordinary skill in the art.

Another subject matter of the present invention are the compounds of formula (Ia): wherein R2, R3, R4, m and n are as defined in general formula (I) and G represents a portion of group A as defined in general formula (I). that is, a covalent bond or the C1-6 alkylene moiety of the -O-C1-6 alkylene group. Among these compounds, mention may be made of: • thiazol-2-ylmethyl 4- (2-hydroxyethyl) piperidine-1-carboxylate • thiazol-4-ylmethyl 3- (hydroxymethyl) pyrrolidine-1-carboxylate.

Another subject matter of the present invention are compounds of general formula (II): wherein A, R 1, R 2, m and n are as defined in general formula (I).

Of these, mention may be made of: • 4- [2- (4-chloronaphth-1-yloxy) ethyl] piperidine • 3- (6-methoxynaphth-2-yloxymethyl) pyrrolidine • 3 '- (pyrrolidin-3 -ylmethoxy) biphenyl-3-carbonitrile • 3- (5-chloronaphth-2-yloxymethyl) pyrrolidine • 3- (3- {trifluoromethoxy} phenoxymethyl) pyrrolidine • 3- [4- (1-methyl-1-phenylethyl) phenoxymethyl] pyrrolidine • 7- (pyrrolidin-3-ylmethoxy) quinoline • 3- (pyrrolidin-3-ylmethoxy) quinoline • 3- (4-chloro-3- {trifluoromethyl} phenoxymethyl) pyrrolidine • 7- (pyrrolidin-3-ylmethoxy) isoquinoline • 3- (5-fluoronaph-2-yloxymethyl) pyrrolidine • 3- (4'-fluorobiphenyl-4-yloxymethyl) pyrrolidine The following examples illustrate the preparation of some compounds of the invention. These examples are not limiting and serve only to illustrate the invention. NMR and / or LC-MS (Liquid Chromatography-Mass Spectroscopy) spectra confirm the structures and purity of the obtained compounds. Mp (° C) represents the melting point in degrees Celsius.

Rf indicates retention time obtained by TLC (Thin Layer Chromatography) analysis.

The numbers shown in parentheses in the example titles correspond to those in the 1st column of the tables below. The International Union of Pure and Applied Chemistry (IUPAC) nomenclature was used to designate the compounds in the examples below. Example 1 (Compound No. 17) Thiazol-4-ylmethyl 3- (naphth-2-yloxymethyl) pyrrolidin-1-carboxylate 1.1 Thiazol-4-ylmethyl 3- (hydroxymethylpyrrolidine-1-carboxylate) A solution of 3.00 g (10.70 mmol) thiazof-4-ylmethyl 4-nitrophenyl carbonate in 20 ml dichloromethane is added at room temperature via a dropping funnel to a solution of 1.13 g (11.24 mmol of pyrrolidin-3-ylmethanol (commercial) in 20 ml of methanol The solution is stirred for 15 hours Water is subsequently added to the reaction medium After extraction of the aqueous phase with dichloromethane, the organic phases are successively washed with a solution of 1 M aqueous sodium hydroxide and then with a saturated aqueous sodium chloride solution After the organic phases are dried over sodium sulfate, the mixture is filtered and the filtrate is evaporated to dryness. of the desired product is thus obtained as an oil after purification over a silica gel column, elution being performed with a dichloromethane / methanol mixture (97/3 to 95/5). 1.2 Thiazol-4-ylmethyl 3- (naphth-2-yloxymethyl) pyrrolidine-1-carboxylate 0.25 g (1.03 mmol) of thiazol-4-ylmethyl 3- (hydroxymethyl) pyrrolidine-1-carboxylate is dissolved in 8 ml of toluene. 0.35 g (1.34 mmol) trifeylphosphine and 0.16 g (1.13 mmol) naphth-2-ol are added and then the medium is cooled to 0 ° C during the slow addition of a solution of 0.27 g (1.34 mmol) of diisopropyl azodicarboxylate in 2 ml of toluene. The medium is stirred at room temperature for 14 hours. The obtained residue is taken up in water and extracted twice with dichloromethane. The combined organic phases are washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated under vacuum. The residue is purified by silica gel chromatography, elution being carried out with a mixture of 99/1 to 98/2 dichloromethane and methanol. 0.15 g of expected product is obtained as a powder. (° C): 90-92 LC-MS: M + H = 369 1H NMR (de-DMSO) δ (ppm): 9.10 (s, 1H); 7.85 (m, 3H); 7.70 (m, 1H); 7.50 (m, 1H); 7.35 (m, 2H); 7.20 (m, 1H); 5.20 (s, 2H); 4.10 (m, 2H); 3.60 (m, 1H); 3.50 (m, 1H); 3.40 (m, 1H); 3.30 (m, 1H); 2.70 (m, 1H); 2.10 (m, 1H); 1.80 (m, 1H) Example 2 (Compound No. 22) Thiazol-4-ylmethyl 3- (4'-fluorobiphenyl-4-yloxymethyl) pyrrolidine-1-carboxylate 2,1S-4-fluorobiphenyl-yloxymethylpyrrolidine-1 tert-Butyl 1-carboxylate The procedure is the same as for example 1 (Stage 1.2) starting from 1.50 g (7.45 mmol) of tert-butyl 3- (hydroxymethyl) pyrrolidine-1-carboxylate (commercial ), 2.15 g (11.18 mmol) of 4'-fluorobiphenyl-4-ol, 2.93 g (11.18 mmol) of triphenylphosphine and 2.26 g (11.18 mmol) of di-azodicarboxylate isopropyl After purification by chromatography on a silica gel column, elution being performed with dichloromethane, 1.55 g of the expected product is obtained as an oil. 2.2 tert-Butyl 3- (4'-fluorobiphenyl-4-yloxymethyl) pyrrolidine 1.55 g (4.17 mmol) of tert-butyl 3- (4'-fluorobiphenyl-4-yloxymethyl) pyrrolidine-1-carboxylate is dissolved in 40 ml of dichloromethane and then at 0 ° C 6.00 ml (80.77 mmol) of trifluoroacetic acid are subsequently added. After stirring at room temperature for two hours, the mixture is concentrated to dryness and then the residue is taken up in water and dichloromethane. A saturated sodium hydrogen carbonate solution is added and then the aqueous phase is extracted with dichloromethane. The combined organic phases are washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated under vacuum. 0.98 g of product is obtained as an oil used as it is in the following stage. 2.3 Thiazol-4-ylmethyl 3- (4'-fluorobiphenyl-4-yloxymethyl) pyrrolidin-1-carboxylate 0.30 g (1.07 mmol) thiazol-4-ylmethyl 4-nitrophenyl carbonate, 0 34 g (1.28 mmol) 3- (4'-fluorobiphenyl-4-yloxymethyl) pyrrolidine, 0.20 g (1.61 mmol) Î ±, β-diisopropylethylamine and 0.01 g ( 0.11 mmol) of dimethylammonopyridine are dissolved in 10 ml of 1,2-dichloroethane. The mixture is stirred at 70 ° C for 4 hours. After returning to room temperature, water is added to the reaction medium. After extraction of the aqueous phase with dichloromethane, the organic phases are successively washed three times with a 1 M aqueous sodium hydroxide solution and then twice with a saturated aqueous ammonium chloride solution. After the organic phases are dried over sodium sulfate, they are filtered off and the filtrate is evaporated to dryness. After purification by chromatography on a silica gel column, elution being performed with dichloromethane and methanol (98/2), 0.16 g of the expected product is obtained as a powder. (° C): 115-117 LC-MS: M + H = 413 1H NMR (de-DMSO) δ (ppm): 9.10 (s, 1H); 7.70 (m, 3H); 7.60 (d, 2H); 7.30 (m, 2H); 7.05 (m, 2H); 5.20 (s, 2H); 4.05 (m, 2H); 3.60 (m, 1H); 3.50 (m, 1H); 3.35 (m, 1H); 3.20 (m, 1H); 2.70 (m, 1H); 2.10 (m, 1H); 1.80 (m, 1H) Example 3 (Compound No. 200) (-) - (R) -3-Carbamoylisoxazol-5-ylmethyl Chiral 3.1 fRV3-fnaft Tert-Butyl -2-yloxymethylPyrrolidine-1-carboxylate The procedure is the same as for example 1 (Stage 1.2) starting from 2.00 g (9.94 mmol) of (R) -3- (hydroxymethyl) pyrrolidine-1 Tert-butyl 1-carboxylate (commercial), 2.00 g (13.91 mmol) naphth-2-ol, 3.90 g (14.91 mmol) triphenylphosphine and 3.01 g (14.91 mmol) ) diisopropyl azodicarboxylate. 1.75 g of product is obtained as an oil after purification on a silica gel column, elution being performed with dichloromethane. 3.2 (R) -3- (naphth-2-yloxymethylpyrrolidine The procedure is the same as for example 2 (Stage 2.2) starting from 1.75 g (5.34 mmol) of (R) -3- (naphth-2 tert-Butyl-1-oxoxymethyl) -pyrrolidine-1-carboxylate and 5.00 ml (67.31 mmol) of trifluoroacetic acid 1.20 g of product is obtained as an oil 3.3 3- 3-nitrophenyl carbonate carbamoylisoxazol-5-ylmethyl 2.84 g (14.07 mmol) 4-nitrophenyl chloroformate are added in small portions to a solution cooled to approximately 0 ° C of 2.00 g (14.07 mmol) of 3 -carbamoylisoxazol-5-ylmethanol, 1.71 ml (21.11 mmol) pyridine and 0.17 g (1.41 mmol) N, α-V-dimethylaminopyridine in 15 ml dichloromethane. at 0 ° C for 1 hour and then at room temperature for 1 hour The precipitate formed is filtered and then rinsed thoroughly with diisopropyl ether 3.12 g (72%) after vacuum drying at approximately 60 ° C ) of the expected product are obtained as a s white oxide used as is in the following stage. Mp (° C): 143-145 1H NMR (de-DMSO, 400 MHz) δ (ppm): 8.40 (d, 2H); 8.25 (broad s, 1H); 7.90 (broad s, 1H); 7.65 (d, 2H); 7.0 (s, 1H); 5.50 (s, 2H). 3-Carbamoylisoxazol-5-ylmethyl (()) -3- (naphth-2-yloxymethyl) pyrrolidine-1-carboxylate (21) (0.92 mmol) (R) -3- (naphth) -2-yloxymethyl) pyrrolidine is dissolved in 3.80 ml of dichloromethane and then 0.31 g (1.01 mmol) of 3-carbamoylisoxazol-5-ylmethyl 4-nitrophenyl carbonate and 0.15 ml (1, 38 mmol) of N-methylmorpholine is added. The mixture is stirred at room temperature for 20 hours and then water is added to the reaction medium. After extraction of the aqueous phase with dichloromethane, the organic phases are successively washed three times with a 1 M aqueous sodium hydroxide solution and then twice with a saturated aqueous ammonium chloride solution. After the organic phases are dried over sodium sulfate, they are filtered off and the filtrate is evaporated to dryness. 0.14 g of the desired product is thus obtained as a white solid after purification on a silica gel column, elution being performed with a dichloromethane / methanol mixture, and then taken up in isopropyl ether. LC-MS: M + H = 396 1H NMR (de-DMSO) δ (ppm): 8.15 (broad s, 1H); 7.80 (m, 4H); 7.50 (m, 1H); 7.35 (m, 2H); 7.20 (m, 1H); 6.80 (s, 1H); 5.30 (s, 2H); 4.10 (m, 2H); 3.65 (m, 1H); 3.50 (m, 1H); 3.40 (m, 1H); 3.30 (m, 1H); 2.80 (m, 1H); 2.10 (m, 1H); 1.85 (m, 1H) [a] 20 C -7.917 ° (c = 0.312; DMSO, 589 nm) Example 4 (Compound No. 202) (+) - (S) -3- (naphth-2-yloxymethyl ) 3-Carbamoylisoxazol-5-ylmethyl pyrrolidine-1-carboxylate tert-Butyl (S) -3- (naphth-2-yloxymethyl) pyrrolidine-1-carboxylate The procedure is the same as for example 1 (Stage 1.2 ) starting from 2.00 g (9.94 mmol) of tert-butyl (S) -3- (hydroxymethyl) pyrrolidine-1-carboxylate (commercial), 2.00 g (13.91 mmol) naphth-2 -ol, 3.90 g (14.91 mmol) triphenylphosphine and 3.01 g (14.91 mmol) diisopropyl azodicarboxylate. 2.80 g of product are obtained as an oil after purification on a silica gel column, elution being performed with dichloromethane. 4.2 (S) -3- (Naphth-2-yloxymethyl) pyrrolidine The procedure is the same as for Example 2 (Stage 2.2) starting from 1.75 g (5.34 mmol) of (S) -3- (naphtho Tert-Butyl 2-yloxymethyl) pyrrolidine-1-carboxylate and 5.00 ml (67.31 mmol) of trifluoroacetic acid. The product is obtained as an oil after purification on a silica gel column, elution being performed with a dichloromethane / methanol / aqueous ammonia (90/9/1) mixture. 4.3 Carbamoylisoxazol-5-ylmethyl (+) - (S) -3- (naphth-2-yloxymethylpyrrolidine-1-carboxylate ______) The procedure is the same as for example 3 (Stage 3.4) starting from 0.21 g (0 (S) -3- (naphth-2-yloxymethyl) pyrrolidine, 95 mmol), 3-carbamoylisoxazol-5-ylmethyl 4-nitrophenyl carbonate (Stage 4.3) and 0 N-methylmorpholine 16 ml (1.42 mmol) 0.21 g of a powder is obtained after purification on a silica gel column, elution being performed with a dichloromethane / methanol mixture, and isopropyl ether trituration. PffC): 139-141 LC-MS: M + H = 396 1H NMR (d0-DMSO) δ (ppm): 8.15 (broad s, 1H); 7.80 (m, 4H); 7.50 (m, 1H); 7.35 (m, 2H); 7.20 (m, 1H); 6.80 (s, 1H); 5.30 (s, 2H); 4.10 (m, 2H); 3.65 (m, 1H); 3.50 (m, 1H); 3.40 (m, 1H); 3.30 (m, 1H); 2.80 (m, 1H); 2.10 (m, 1H); 1.85 (m, 1H) [α] 20 ° C + 9.944 ° (c = 0.036; DMSO, 589 nm) The chemical structures and physical properties of some compounds according to the invention are illustrated in the following table 1. In this table, the compounds are in free base or salt form. A represents a -O-C 1-6 alkylene group in which the end represented by an oxygen atom is attached to the R 1 group.

Table 1 The results of the 1 H NMR analyzes and melting points (Pf) for the compounds in table 1 are provided in the following table 2. Table 2 Results for M + H masses measured by LC-MS and retention times for compounds in table 1 are provided in the following table 3.

LC-MS Conditions: Method A: HPLC / ZQ - Gradient 10 min Mobile Phases: Phase A: CH3COONH4 + 3% ACN Phase B: ACN

Column / stationary phase: Kromasil C18 column Dimensions: 50 * 2.1 mm; 3.5 pm Flow rate: D = 0.8 ml / min Column temperature: T = 40 ° C Injection volume: V = 5 pl Gradient: T = 0 min: 100% A, T = 5, 5 min at T = 7 min: 100% B, T = 7.1 min at T = 10 min: 100% A. Method B: UPLC / TOF - Gradient 3 min Mobile Phases: Phase A: H2 O + 0 0.05% TFA Phase B: ACN + 0.035% TFA

Stationary column / phase: Acquity BEH C18 column Dimensions: 50 * 2.1 mm; 1.7 μιτι Flow rate: D = 1.0 ml / min Column temperature: T = 40 ° C

Injection volume: V = 2 pl Gradient: T = 0 min: 98% A and 2% B, from T = 1.6 min to T = 2.1 min: 100% B, from T = 2, 5 min at T = 3 min: 98% A and 2% B. Method C: LC / TRAP - Gradient 20 min Mobile Phases: H20 / CH3C00NH4 / ACN

Stationary column / phase: Kromasil C18 column Method D: LC / ZQ - Gradient 20 min Mobile Phases: TFA / ACN

Stationary column / phase: Kromasil C18 column Method E: LC / TOF - Gradient 20 min Mobile Phases: H20 / CH3C00NH4 / ACN

Stationary column / phase: Kromasil C18 column Method F: Stationary column / phase: Jsphere Dimensions: 33 * 2 mm; 4 pm Gradient: H2 O + 0.05% TFA: ACN + 0.05% TFA; 2:98 (1 min) at 95: 5 (5.0 min) at 95: 5 (6.25 min). Method G: Column / Stationary Phase: Waters XBridge C18 Dimensions: 4.6 * 50 mm; 2.5 pm Gradient: H2 O + 0.05% TFA: ACN + 0.05% TFA; 95: 5 (0 min) to 95: 5 (0.3 min) to 5:95 (3.5 min) to 5:95 (4 min). Method H: YMC

Stationary column / phase: Jsphere Dimensions: 33 * 2 mm; 4 μιτ>

Gradient: H2 O + 0.1% TFA: ACN + 0.08% TFA; 95: 5 (0 min) to 5:95 (2.5 min) to 5:95 (3 min).

The compounds of the invention form the subject of pharmacological experiments which make it possible to determine their inhibitory effect on the FAAH (Fatty Acid Hydrolase Amide) enzyme. 1 / Radioenzymatic Test Inhibitory activity was demonstrated in a radioenzymatic test based on the measurement of anandamide hydrolysis product [ethanolamine 1 -3H] by FAAH (Life Sciences (1995), 56, 1999-2005 and Journal of Biochemi-cal and Biophysical Methods (2004), 60 (2), 171-177). In this way mouse brains (minus the cerebellum) are removed and stored at -80 ° C. Membrane homogenates are prepared at the time of use by tissue homogenization using a Precellys® device in the reaction buffer (Tris-HC110 mM pH = 8, 150 mM NaCl and 1 mM ethylenediaminetetraacetic acid (EDTA)). The enzymatic reaction is performed in 96-well MultiScreen filtration plates in a final volume of 70 pl. Reaction buffer supplemented with fatty acid free bovine serum albumin (BSA, 1 mg / ml) is used for enzyme reaction, compound dilution and anandamide dilution [1-3H ethanolamine]. The reaction buffer comprising BSA (43 pl / well), test compounds diluted at different concentrations (7 μΙ / well comprising 1% DMSO) and membrane preparation (10 pl / well ie 200 pg tissue). by experiment) are successively added to the wells. After preincubation of the compounds with the enzyme at 25 ° C for 20 minutes, the reaction is initiated by the addition of anandamide [ethanolamine 1-3H] (specific activity 15-20 Ci / mmol) diluted with cold anandamide (10 pl / ml). well, final concentration 10 pM, 0.01 pCi, per experiment). After incubation at 25 ° C for 20 minutes, the enzymatic reaction is stopped by the addition of a 5 M active charcoal solution prepared in a 1.5 M NaCl buffer and 0.5 M HCl (50 µl / well ). The mixture is stirred for 10 minutes and then the aqueous phase comprising [1-3 H] ethanolamine is recovered by vacuum filtration and counted by liquid scintillation.

Under these conditions, the most active compounds of the invention exhibit IC 50 values (concentration which inhibits FAAH control enzyme activity by 50%) between 0.1 and 1000 nM, preferably between 0.1 and 500 nM, preferably between 0.2 and 100 nM, indeed even between 0.2 and 50 nM. For example, compounds No. 26, No. 38, No. 39, No. 49, No. 60, No. 90, No. 196, No. 199, No. 200 and No. 202 have respective IC50 values of 86 nM, 14 nM, 13 nM, 19 nM, 95 nM, 92 nM, 252 nM, 350 nM, 122 nM and 8 nM. It is thus evident 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 may be evaluated in an analgesia test. 2 / Test for analgesia Intraperitoneal (ip) administration of PBQ (phenylbenzoquinone, 2 mg / kg in a 0.9% sodium chloride solution comprising 5% ethanol) to male OF1 mice weighing 25 to 30 g causes abdominal traction , on average 30 flexion or contraction movements during the period of 5 to 15 minutes after injection. Test compounds are administered orally (p.o.) or intraperitoneally (i.p.) in suspension in 0.5% Tween 80, 60 minutes or 120 minutes prior to administration of PBQ. Under these conditions, the most powerful compounds reduce the number of pulls induced by PBQ by 30 to 80% within a dose range of 1 to 30 mg / kg. The enzyme FAAH (Chemistry and Physics of Lipids, (2000), 108, 107-121) catalyzes the hydrolysis of endogenous derivatives of amides and esters of various fatty acids, such as N-arachidonylethanolamine (anandami-da), / V-palmitoylethanolamine. N-oleylethanolamine, oleamide or 2-arachidonoylglycerol. These derivatives perform various pharmacological activities by interacting, among other things, with cannabinoid and vanilloid receptors.

The compounds of the invention block this pathway of decomposition and increase the tissue level of these endogenous substances. They can therefore be used to prevent and treat conditions in which endogenous cannabinoids and / or any other substrate metabolised by the FAAH enzyme are involved. Mention may be made, for example, of the following diseases and conditions: pain, in particular acute or chronic neurogenic pain: migraine, neuropathic pain, including forms associated with herpes virus and diabetes and chemotherapy; acute or chronic pain associated with inflammatory diseases: arthritis, rheumatoid arthritis, osteoarthritis, spondylitis, gout, vasculitis, Crohn's disease, irritable bowel syndrome; acute or chronic peripheral pain; dizziness, vomiting, nausea, in particular resulting from chemotherapy; eating disorders, in particular anorexia and cachexia of various kinds; neurological and psychiatric disorders: tremors, dyskinesias, dystonias, spasticity, obsessive-compulsive behavior, Tourette's syndrome, all forms of depression and anxiety of any nature and origin, mood disorders, psychoses; acute or chronic neurodegenerative diseases: Parkinson's disease, Alzheimer's disease, senile dementia, Huntington's chorea, lesions related to cerebral ischemia and head and spinal cord trauma; epilepsy; sleep disorders, including sleep apnea; cardiovascular diseases, in particular hypertension, cardiac arrhythmias, arteriosclerosis, heart attack, cardiac ischemia; renal ischemia; cancers: benign skin tumors, brain tumors and papillomas, prostate tumors, brain tumors (glioblastomas, meduloepitheliomas, medulloblastomas, neuroblastomas, tumors of embryonic origin, astrocytomas, astroblastomas, ependymomas, oligodendrogliomas, tumors of the tumor, epiphyseal, ependymoblastomas, malignant meningiomas, sarcomatosis, malignant melanomas, schwannomas); disorders of the immune system, in particular autoimmune diseases: psoriasis, lupus erythematosus, connective tissue diseases or collagen diseases, Sjogren's syndrome, ankylosing spondylitis, undifferentiated spondylitis, Behcet's disease, autoimmune haemolytic anemia, multiple sclerosis, amyotrophic lateral sclerosis, , graft rejection, diseases that affect the plasmacytic lineage; allergic diseases: immediate or delayed hypersensitivity, allergic rhinitis or conjunctivitis, contact dermatitis; parasitic, viral or bacterial infectious diseases: AIDS, meningitis; inflammatory diseases, in particular joint diseases: arthritis, rheumatoid arthritis, osteoarthritis, spondylitis, gout, vasculitis, Crohn's disease, irritable bowel syndrome; osteoporosis; eye conditions: ocular hypertension, glaucoma; pulmonary conditions: respiratory tract diseases, bronchospasm, cough, asthma, chronic bronchitis, chronic obstruction of the respiratory tract, emphysema; gastrointestinal disorders: irritable bowel syndrome, inflammatory bowel disorders, ulcers, diarrhea; urinary incontinence and bladder inflammation. The use of the compounds according to the invention, in the form of the base, of a pharmaceutically acceptable acid, hydrate or solvate addition salt, in the preparation of a medicament for treating the above-mentioned conditions forms a integral part of the invention.

Compounds according to the invention, in the form of the base, an acid addition salt, a hydrate or a solvate which is pharmaceutically acceptable for use in the preparation of a medicament for treating the above-mentioned conditions form a integral part of the invention.

Another subject matter of the invention is medicaments comprising a compound of formula (I), (li) or (lii), or an acid addition salt, or a hydrate or solvate which is pharmaceutically acceptable from the compound of formula (I ), (li) or (lii). These medicaments are therapeutically used, in particular in the treatment of the conditions mentioned above.

According to another aspect thereof, the present invention relates to pharmaceutical compositions comprising as active ingredient at least one compound according to the invention. These pharmaceutical compositions comprise an effective dose of a compound according to the invention, or an addition salt with an acid, or a hydrate, or a solvate which is pharmaceutically acceptable from said compound, and optionally one or more pharmaceutically acceptable excipients.

Said excipients are chosen, depending on the pharmaceutical form and desired method of administration, from the usual excipients which are known to a person 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), (li) or (lii) above or its optional addition salt with an acid, solvate or hydrate may be administered in unit dosage form, as a mixture with conventional pharmaceutical excipients, to animals and man for the prophylaxis or treatment of the above disorders or diseases.

Suitable unit administration forms include oral forms such as tablets, soft or hard gelatin capsules, powders, granules, chewing gums and oral solutions or suspensions, form for sublingual, buccal, intratracheal, intraocular or intranasal administration or for administration by inhalation. forms for subcutaneous, intramuscular or intravenous administration and forms for rectal or vaginal administration. For topical application, the compounds according to the invention may be used in creams, ointments or lotions.

By way of example, a unit administration form of a compound according to the invention in tablet form may comprise the following components: Compound according to the invention 50.0 mg Mannitol 223.75 mg Croscarmellose sodium 6.0 mg Maize starch 15.0 mg Hydroxypropyl methylcellulose 2.25 mg Magnesium stearate 3.0 mg These unit forms comprise a dose which makes it possible to daily administer 0.01 to 20 mg of active ingredient per kg body weight, depending on the pharmaceutical dosage form.

There may be specific cases where higher or lower dosages are appropriate; Such dosages also come into the invention. In accordance with standard practice, the appropriate dosage for each patient is determined by the doctor according to the method of administration and the weight and response of said patient.

According to another of its aspects, the invention also relates to a method for treating the conditions indicated above which comprises administering an effective dose of a compound according to the invention, one of its addition salts with a pharmaceutically acceptable acid or a solvate or hydrate of said compound.

Claims (15)

1. Compound corresponding to the general formula (I): (Wherein: R2 represents a hydrogen or fluorine atom or a hydroxyl, cyano, trifluoromethyl, C1-6 alkyl, C1-6 alkoxy or -NR6 R6 group; and independently of one another an integer of 1, 2 or 3, the sum being m + n being at most 5; - A represents a covalent bond, an oxygen atom, a C1-6 alkylene group or a -O-C1- e-alkylene group in whereas the end represented by an oxygen atom is attached to the group R1; R5 represents a group R5 optionally substituted by one or more groups Re and / or R7; R5 representing a group selected from phenyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, naphthyl, quinolinyl, isoquinolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, cinolinyl, naphthyridinyl, benzothiazolyl, benzisotothiazole, benzoxazolyl, benzisoxazolyl, benzimidazolyl, benzoburanyl, benzoburanyl benzophenyl benzyluranyl benzophenyl benzyl , Indolyl, isoindolila, imidazopiridinila, imidazopirimidinila, imidazo-pyrazinyl, imidazopiridazinila, triazolopiridinila, pirrolopiridinila, pirrolopirimidi-nila, pirrolopirazinila, pirrolopiridazinila, pirrolotriazinila, pirazolopiridinila pi-razolopirimidinila, pirazolopirazinila, pirazolopiridazinila, furopiridinila, furopi-rimidinila, furopirazinila, furopiridazinila, furotriazinila , oxazolopiridinila, oxa-zolopirimidinila, oxazolopirazinila, oxazolopiridazinila, isoxazolopiridinila, iso-xazolopirimidinila, isoxazolopirazinila, isoxazolopiridazinila, oxadiazolopiridi-nila, tienopiridinila, tienopirimidinila, tienopirazinila, tienopiridazinila, tienotria-zinila, tiazolopiridinila, tiazolopirimidinila, tiazolopirazinila, tiazolopiridazinila, isotiazolopiridinila, isotiazolopirimidinila, isotiazolopirazinila isothiazolopyridinyl or thiadiazolopyridinyl; R 6 represents a halogen atom or a cyano group, -CH 2 CN, nitro, hydroxyl, C 1-8 alkyl, C 1-6 alkoxy, C 1-6 thioalkyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 1-6 halothioalkyl, C3-7-cycloalkyl, C3.7-cyclo-C1-3 alkylphenyl, C3-7-cycloalkyl-C1-3 alkylene-0-, - (CH2) P-NR8R9, -NRgCORg, -NReCO2R9, -NR8SO2Rg, -NR8SO2NR8Rg -COR 8, -G 2 R 8, - (CH 2) p -CONR 8 R 9, -SO 2 R 8 I -SO 2 NR 8 R 9 or -0- (C 1-3 alkylene) -0-; R7 representing a group selected from phenyl, phenyl-C-1-4-alkylene-, phenyl- (CH2) p-O-, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, furanyl, thienyl, imidazolyl, oxazolyl, isoxazolyl , pyrrolyl, pyrazolyl, te-bringolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, imidazopyrimidinyl, thienopyrimidinyl, benzofuranyl, benzothienyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzisothiazolylindiimidazole, thiazolylidazole, thiazolylidazole pyrazolopyridinyl, oxazolopyridinyl, isoxazolopyridinyl or thiazolopyridinyl; being possible for the group or groups R7 to be substituted by one or more groups R6 which are identical to or different from each other; p represents a number which may have the value 0, 1, 2 or 3; R3 represents a hydrogen or fluorine atom, a C1-8 alkyl group or a trifluoromethyl group; R4 represents a 5-membered heterocycle chosen from furanyl, pyrrolyl, thienyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyrazolyl, o-xadiazolyl, thiadiazolyl, imidazolyl, triazolyl or tetrazolyl; this heterocycle optionally being substituted by one or more substituents selected from a halogen atom or a C1-6-alkyl, C1-6-haloalkyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-3 alkylene group, C1-6 -haloalkoxy, cyano, -NR 8 R 9, -NR 8 C (0) R 9, -NR 8 CO 2 R 9, -NR 8 SO 2 R 9, -NR 8 SO 2 NR 8 R 9, -C (0) R s, -C 2 R 8) -C (0) NR 8 R 9, -CCOJNIRsKC 4 α-alkylene-NR 10 R 7 , -SO 2 R 8, -SO 2 NR 8 R 9 or -O-C 1 s -alkylene; R8 and R9 independently representing a hydrogen atom or a C1-6 alkyl group, or forming with the nitrogen atom or atoms which carry them, in the case of NReRg, a ring chosen from the azetidine rings, pyrrolidine, piperidine, morpholine, thiomorpholine, azepine, oxazepine or piperazine, this ring optionally being substituted by a C1-6 alkyl or benzyl group; in the case of NReCORg, a lactam ring; in the case of NR 8 CO 2 R 9, an oxazolidinone, oxazinone or oxazepinone ring; in the case of NR8SO2R9 a ring results; in the case of NRaSC4 NReRg, a thiazolidine dioxide or thiadiazinane dioxide ring; R 10 and R 11 independently of one another represent a hydrogen atom or a C 1 -C 6 alkyl group; excluding the following compound: 5-methylisoxazol-3-ylmethyl 4-hydroxy-4- (4-chlorophenyl) piperidine-1-carboxylate as the base or an acid addition salt. Compound of formula (I) according to claim 1, characterized in that R2 represents a hydrogen atom; in the form of the base or an addition salt with an acid. Compound of formula (I) according to Claim 1 or 2, characterized in that m and n independently represent 1 or 2; in the form of the base or an addition salt with an acid. Compound of formula (I) according to any one of the preceding claims, characterized in that A represents a -O-C 1-6 alkylene group wherein the end represented by an oxygen atom is attached to the group R 1; in the form of the base or an addition salt with an acid. Compound of formula (I) according to any one of the preceding claims, characterized in that R1 represents a group R5 optionally substituted by one or more groups R6 and / or R7; Rs representing a selected group of phenyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, naphthyl, quinolinyl, isoquinolinyl, phthalazinyl, quinoxalinyl, quinazolinyl, cinolinyl, naphthyridinyl, benzothiazolyl, benzoxazol, benzoxazol, benzoxazol isobenzofuranyl, benzofuranyl, benzothiophenyl, indazolyl, indolizinyl, indoiyl, isoindolyl, pyrro-lopyridinyl, furopyridinyl or thienopyridinyl; Re represents a halogen atom or a cyano group, -CH 2 CN, nitro, hydroxyl, C 1-8 alkyl, C 1-6 alkoxy, C 1-6 thioalkyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 1-6 halothioalkyl, C 3-7 cycloalkyl, C 3-7 cycloalkylC 1-3 alkylene, C 3-7 cycloalkylC 1-3 alkylene-O-, (CH 2) P-NR 8 R 9, -NR 8 COR 9, -NR 8 CO 2 R 9, - NR 8 SO 2 R 9, -NR 8 SO 2 NR 8 R 9, -CORa, -C 2 R 8) - (CH 2) p -CONR s R 9, -SO 2 R 8, -SO 2 NR 8 R 9 or -0- (C 1-3 alkylene) -0-; R 7 represents a group selected from phenyl, phenyl-C 1-4 alkylene-, phenyl- (CH 2) p -0-, pyridinyl, pyridazinyl, isoxazolyl, benzothiazolyl, pyrrolyl, pyrazolyl, tetrazolyl, pyrimidinyl, thiazolyl, pyrazinyl, triazinyl or benzoxazolyl; being possible for the group or groups R7 to be substituted by one or more groups Re, which are identical to or different from each other as defined above; p represents a number which may have the value 0, 1, 2 or 3; R5 and R9 independently of one another represent a hydrogen atom or a C1-6 alkyl group; or forming, with the nitrogen atom or atoms carrying them, in the case of NR8R9, a ring chosen from the rings azetidine, pyrrolidine, piperidine, morpholine, thiomorpholine, azepine, oxazepine or piperazine, this ring optionally being substituted by a group. C 1-6 alkyl or benzyl; in the case of NR8COR9, a lactam ring; in the case of NR 8 CO 2 R 9, an oxazolidinone, oxazinone or oxazepinone ring; in the case of NR8S02R9, a ring results; in the case of NR8 SO2 NR8 R9, a thiazolidine dioxide or thiadiazinane dioxide ring; in the form of the base or an addition salt with an acid. Compound of formula (I) according to any one of the preceding claims, characterized in that R 3 represents a hydrogen atom; in the form of the base or an addition salt with an acid. Compound of formula (I) according to any one of the preceding claims, characterized in that R4 represents a 5-membered heterocycle chosen from thiazolyl or isoxazolyl; this heterocycle optionally being substituted by one or more substituents of -C (O) NR 8 R 9 wherein R 8 and R 6 each represent a hydrogen atom; in the form of the base or an addition salt with an acid. A compound of formula (I) according to claim 1 which is selected from the following compounds: thiazol-2-ylmethyl 4- [2- (4-chloronaph-1-yloxy) ethyl] piperidine-1-carboxylate - Thiazol-2-ylmethyl [2- (4-fluorophenoxy) ethyl] piperidine-1-carboxylate 4- [2- (4-fluorophenoxy) ethyl] thiazol-4-ylmethyl 4- [2- (4-fluorophenoxy) ethyl] piperidine-carboxylate Thiazol-4-ylmethyl (4- {trifluoromethyl} phenoxy) ethyl] piperidine-1-carboxylate 4- [2- (4-chlorophenoxy) ethyl] thiazol-4-ylmethyl 4- [2- ( Thiazol-5-ylmethyl 4-fluorophenoxy) ethyl] piperidine-1-carboxylate 4- [2- (4-chlorophenoxy) ethyl] thiazol-5-ylmethyl 4- [2- (4- {trifluoromethyl] 4- [2- (4- {trifluoromethyl) piperidine } thiazol-5-ylmethyl 4- [2- (7-methoxynaphth-2-yloxy) ethyl] thiazol-4-ylmethyl 4- [2- (4-phenoxy) -phenyl-piperidine-1-carboxylate thiazol-4-ylmethyl (+/-) -3- (6-methoxynaph-2-yloxymethyl) pyrrolidine-1-carboxylate of thiazol-4-ylmethyl (+/- ) -3- (7-methoxynaphth-2-yloxymethyl) p thiazol-4-ylmethyl (+/-) -3- (3,4-dichlorophenoxymethyl) pyrrolidine-1-carboxylic acid thiazol-4-ylmethyl 4- [2- (6-methoxynaphth-2-carboxylate) thiazol-4-ylmethyl-4- [2- (naphth-2-yloxy) ethyl] -piperidine-1-thiazol-4-ylmethyl (+/-) -3- (thiazol-4-ylmethyl) piperidine-1-carboxylate Thiazol-4-ylmethyl (+/-) -3- (naphth-2-yloxymethyl) pyrrolidine-1-carboxythiazol-4-ylmethyl 4-chloronaphth-1-yloxymethyl) pyrrolidine-1-carboxylate 4- [2- Thiazol-4-ylmethyl (4'-fluorobiphenyl-4-yloxy) ethyl] piperidine-1-carboxylate 4- [2- (quinolin-6-yloxy) ethyl] piperidine-1-carboxylate of thiazol-4-ylmethyl and its thiazol-4-ylmethyl 4- [2- (isoquinolin-6-yloxy) ethyl] piperidine-1-carboxylate hydrochloride and its (+/-) -3- (3'-cyanobiphenyl-3-yloxymethyl) pyrrolidine-1 hydrochloride thiazol-4-ylmethyl (+/-) -3- (4'-fluorobiphenyl-4-yloxymethyl) pyrrolidin-1-thiazol-4-ylmethyl (+/-) -3- (carboxylate) carboxylate Thiazol-4-ylmethyl (+/-) -3- (3- {trifluoromethyl 5-chloronaph-2-yloxymethyl) pyrrolidin-1-carboxylate xi} thiazol-4-ylmethyl (+/-) -3- [4- (1-methyl-1-phenylethyl) phenoxymethyl] pyrrolidine-1-carboxylic acid thiazol-4-ylmethyl (+ / -) - Thiazol-4-ylmethyl 3- (quinolin-3-yloxymethyl) pyrrolidine-1-carboxylate (+/-) -3- (thiazol-4-ylmethyl isoquinolin-6-yloxymethyl) pyrrolidine-1-carboxylate Thiazol-4-ylmethyl (+/-) -3- (quinolin-7-yloxymethyl) pyrrolidine-1-carboxylate (+/-) -3- (thiazol-4-isoquinolin-7-yloxymethyl) pyrrolidine-1-carboxylate (+/-) -3- (4-chloro-3- {trifluoromethyl} phenoxymethyl) pyriazolid-1-carboxythiazol-4-ylmethyl (+/-) -3- (5-fluoronaph-2-yloxymethyl) thiazol-4-ylmethyl 4- [2- (2,4-dimethylphenoxy) ethyl] piperidine-1-thiazol-2-ylmethyl pyrrolidine-1-carboxylate 4- (2- (2,3-dichlorophenoxy) ethyl] thiazol-2-ylmethyl piperidine-1-carboxylate 4- [2- (2,4-dichlorophenoxy) ethyl] thiazol-2-ylmethyl piperidine-1-carboxylate 4- (2- (2,5-dichlorophenoxy) ethyl] thiazol-2-ylmethyl piperidine-1-carboxylate 4- (2- (3,4-dichlorophenoxy) ethyl] pipe thiazol-2-ylmethyl ridine-1-carboxylate 4- (2- (3,5-dichlorophenoxy) ethyl] piperidine-thiazol-2-ylmethyl 4- (2- (4-cyclopentylphenoxy) ethyl] piperidine-1-carboxylate Thiazol-2-ylmethyl 4- [2- (2- {benzoxazol-2-yl} phenoxy) ethyl] piperidine-1-thiazol-2-ylmethyl 1-carboxylate 4- [2- (4- { benzyloxy} phenoxy) ethyl] thiazol-2-ylmethyl 4- [2- (4- {carbamoylmethyl} phenoxy) ethyl] thiazol-2-ylmethyl 4- [2- (4- {carbamoylmethyl} phenoxy) ethyl] piperidine-1-carboxylate 4- (2- thiazol-2-ylmethyl (quinolin-7-yloxy) ethyl] piperidine-1-carboxylate and its trifluoroacetate thiazol-2-ylmethyl 4- [2- (quinolin-6-yloxy) ethyl] piperidine-1-carboxylate and its thiazol-2-ylmethyl 4- [2- (4-cyano-3-fluorophenoxy) ethyl] piperidine-1-carboxylate trifluoroacetate 4- [2- (biphenyl-2-yloxy) ethyl] thiazol-piperidine-1-carboxylate Thiazol-2-ylmethyl 4- [2- (2-isopropyl-5-methylphenoxy) ethyl] piperidine-1-carboxylate 4- [2- (3- {trifluoromethyl} phenoxy) ethyl] piperidine-1-2-ylmethyl 4- {2- [4- (1,1,3,3-tetramet-thiazol-2-ylmethyl] -carboxylate thiazol-2-ylmethyl yl] -phenoxy] ethyl} -piperidine-1-carboxylate 4- [2- (4-benzylphenoxy) ethyl] thiazol-2-methyl-4- [2- (4- {pyrrolidinyl) -4- Thiazol-2-ylmethyl 1-yl} phenoxy) ethyl] piperidine-1-carboxylate and its 4- [2- (4-carbamoylphenoxy) ethyl] piperidine-1-carboxylate and thiazol-2-ylmethyl 4- [2- Thiazol-2-ylmethyl (3-cyanophenoxy) ethyl] piperidine-1-carboxylate 4- [2- (3,5-di {tert-butyl} phenoxy) ethyl] thiazol-2-ylmethyl 4- piperidine-1-carboxylate 4 Thiazol-2-ylmethyl [2- (2-benzylphenoxy) ethyl] piperidine-1-carboxylate thiazol 4- [2- (8- {acetylamino} naphth-2-yloxy) ethyl] piperidine-1-carboxylate 2-ylmethyl 4- [2- (3- {methoxycarbonyl} naphth-2-yloxy) ethyl] thiazol-2-ylmethyl 4- [2- (3-phenoxyphenoxy) ethyl] piperidine-1-carboxylate thiazol-2-ylmethyl 4- [2- (isoquinolin-7-yloxy) ethyl] piperidine-1-thiazol-2-ylmethyl carboxylate and its trifluoroacetate 4- [2- (4-hexyloxyphenoxy) ethyl] piperidine-1 4- [2- (3-buto-thiazol-2-ylmethyl] -carboxylate thiazol-2-ylmethyl 4- [2- (quinolin-5-yloxy) ethyl] piperidine-1-thiazol-2-ylmethyl xylphenoxy) ethyl] piperidine-1-carboxylate and its 4- [2- (3) trifluoroacetate thiazol-2-ylmethyl 4- {2- (5- {acetylamino} naphth-2-yloxy) ethyl] piperidine-1-carboxylate thiazol-2-ylmethyl} piperidine-1-carboxylate Thiazol-2-ylmethyl 4- [2- (2-methylquinolin-6-yloxy) ethyl] piperidine-1-carboxylate 4- [2- (5-bromo-2-chlorophenoxy) ethyl] piperidine-1-carboxylate 4- [2- (4,4-cyanobiphenyl-3-yloxy) ethyl] piperidine-1-thiazol-2-ylmethyl 4- [2- (6-cyanonaphth-2-yloxy] trifluoroacetate and its trifluoroacetate thiazol-2-ylmethyl] ethyl] piperidine-1-carboxylate 4- [2- (4- {thiazo-2-N} phenoxy) ethyl] thiazol-2-ylmethyl] 4- [2- thiazol-2-ylmethyl 4- [2- (biphenyl-4-yloxy) ethyl] piperidine-1-thiazol-2-ylmethyl (biphenyl-3-yloxy) ethyl] piperidine-1-carboxylate 4- [2- Thiazol-2-ylmethyl (2-cyanoquinolin-8-yloxy) ethyl] piperidine-1-carboxylate 1a and its thiazol-2-ylmethyl 4- [2- (4-chloro-2-cyanophenoxy) ethyl] piperidine-1-carboxylate trifluoroacetate and its 4- [2- (2-methylbenzothiazol-5-yloxy) ethyl] trifluoroacetate thiazol-2-ylmethyl 4- [2- (4'-cyanobiphenyl-4-yloxy) ethyl] thiazol-2-ylmethyl piperidine-1-carboxylate 4- [2- (2- { thiazol-2-ylmethyl 4- [2- (4-chloro-2- {isoxazol-5-yl} phenoxy) ethyl] piperidine-1-carboxylate morpholin-4-yl} phenoxy) ethyl] piperidine-1-carboxylate thiazol-4-ylmethyl 4- [2- (2,4-dimethylphenoxy) ethyl] piperidine-1-carboxythiazol-4-ylmethyl 4- [2- (2,3-dichlorophenoxy) ethyl] piperidine-1-carboxyate thiazol-4-ylmethyl 4- [2- (naphth-1-yloxy) ethyl] piperidine-1-thiazol-4-ylmethyl 4- [2- (3- {dimethylamino} phenoxy) ethyl] piperidine-1-carboxylate of thiazol-4-ylmethyl and its trifluoroacetate 4- [2- (3- {trifluoromethyl} phenoxy) ethyl] piperidine-1-carboxylate thiazol-4-ylmethyl 4- [2- (4-benzylphenoxy) ethyl] piperidine-1 4- [2- (2-ethoxyphenoxy) ethyl] piperyl-thiazol-4-ylmethyl-carboxylate thiazol-4-ylmethyl 4- {2- [4- (1-methyl-1-phenylethyl) phenoxy] ethyl} piperidin-1-carboxyate thiazol-4-ylmethyl 4- [2- (4 thiazol-4-ylmethyl 4- [2- (2-bromo-4-fluorophenoxy) ethyl] piperidine-1-carboxythiazol-4-ylmethyl 4- [2- (2-bromo-4-fluorophenoxy) ethyl] piperidine-1-carboxylate 4- [2- Thiazol-4-ylmethyl (2-benzylphenoxy) ethyl] piperidine-1-carboxylate 4- [2- (3-phenoxyphenoxy) ethyl] thiazol-4-ylmethyl 4- [2- (4- { thiazol-4-ylmethyl 4- [2- (3-butoxyphenoxy) ethyl] piperidine-1-carboxythiazol-4-ylmethyl] 4- [2- (4-chloro) Thiazol-4-ylmethyl 4- [2- (3- {pentafluoroethyl} phenoxy) ethyl] piperidine-1-carboxythiazol-4-ylmethyl 5-isopropyl-2-methylphenoxy) ethyl] piperidine-1-carboxylate 4 - Thiazol-4-ylmethyl 4- [2- (5-bromo-2-chlorophenoxy) ethyl] piperidine-1 - [2- (5- {acetylamino} naphth-2-yloxy) ethyl] piperidine-1-carboxylate thiazol-4-ylmethyl 4- [2- (4'-cyanobiphenyl-3-yloxy) ethyl] piperidine-1-carboxylate dicarboxylate d and thiazol-4-ylmethyl 4- [2- (6-cyanonaphth-2-yloxy) ethyl] piperidine-1-carboxylate thiazol-4-ylmethyl 4- [2- (4- {thiazol-2-yl} phenoxy) thiazol-4-ylmethyl ethyl] piperidin-1-carboxylate 4- [2- (biphenyl-3-yloxy) ethyl] thiazol-4-ylmethyl 4- [2- (biphenyl-4-yloxy)] piperidine-1-carboxylate 4- [2- (4-Chloro-2-cyanophenoxy) ethyl] -thiazol-4-ylmethyl-4- [2- (2-methylbenzothiazol-4-yl) -piperidine-1-carboxylate Thiazol-4-ylmethyl 4- [2- (4'-cyanobiphenyl-4-yloxy) ethyl] piperidine-1-carboxythiazol-4-ylmethyl 5-yl [4-ylmethyl] piperidine-1-carboxylate 4- [ Thiazol-4-ylmethyl 2- (2- {morpholin-4-yl} phenoxy) ethyl] piperidin-1-carboxylate and its trifluoroacetate 4- [2- (4-chloro-2- {isoxazol-5-yl} phenoxy thiazol-4-ylmethyl] ethyl] piperidine-1-carboxylate 4- [2- (4- {dimethylaminomethyl} phenoxy) ethyl] thiazol-2-ylmethyl] piperidine-1-carboxylate and its 4- [2- (naphtho] trifluoroacetate Thiazol-2-ylmethyl-2- [2- (naphth-1-yloxy) ethyl] -piperidine-1-carbothiazol-2-yl] -piperidine-1-carboxylate thiazol-2-ylmethyl 4- [2- (7-methoxynaph-2-yloxy) ethyl] piperidine-1-thiazol-2-ylmethyl] 4- [2- (2-cyclopertylphenoxy) ethyl] piperidine-1-oxide oxylate thiazol-4-ylmethyl 4- [2- (2-benzyloxyphenoxy) ethyl] piperidine-1-carboxylic acid thiazol-4-ylmethyl 4- [2- (isoquinolin-7-yloxy) ethyl] piperidine-1-carboxylate carboxylate thiazol-4-ylmethyl and its trifluoroacetate 4- [2- (quinolin-5-yloxy) ethyl] piperidine-1-carboxylate thiazol-4-ylmethyl and its 4- [2- (2-methylquinolin-6-yloxy) trifluoroacetate thiazol-4-ylmethyl ethyl] piperidin-1-carboxylate and its trifluoroacetate 4- [2- (2-cyanoquinolin-8-yloxy) ethyl] thiazol-4-ylmethyl 4- piperidine-1-carboxylate and its trifluoroacetate 4- [2 - Thiazol-4-ylmethyl (2,4-dichlorophenoxy) ethyl] piperidine-1-carboxylate 4- [2- (4-cyclopentylphenoxy) ethyl] thiazol-4-ylmethyl 4- piperidine-1-carboxylate 4- [2- ( Thiazol-4-ylmethyl 2- [benzoxazol-2-yl} phenoxy) ethyl] piperidine-1-carboxylate thiazol-4- [2- (4-cyano-3-fluorophenoxy) ethyl] piperidine-1-carboxylate 4-ilme thiazol-4-ylmethyl 4- {2- [4- (1,1,3,3-tetramethylbutyl) phenoxy] ethyl} piperidine-1-carboxylate 4- [2- (4- {pyrrol-1-yl}} thiazol-4-ylmethyl phenoxy) ethyl] piperidine-1-carboxylate and its thiazol-4-ylmethyl 4- [2- (3,5-di {tert-butyl} phenoxy) ethyl] piperidine-1-carboxylate 4 - Thiazol-4-ylmethyl [2- (4- {dimethylaminomethyl} phenoxy) ethyl] piperidine-1-carboxylate and its trifluoroacetate 4- [2- (2-methylquinolin-8-yloxy) ethyl] piperidine-1-carboxylate thiazol-4-ylmethyl and its thiazol-4-ylmethyl 4- [2- (3-cyanophenoxy) ethyl] piperidine-1-carboxylate thiazol-5-ylmethyl 4- (2-phenoxyethyl) piperidine-1-carboxylate 4 - Thiazol-5-ylmethyl 4- [2- (4-carbamoylphenoxy) ethyl] piperidine-1-carboxythiazol-5-ylmethyl 4- [2- (biphenyl-4-yloxy) ethyl] piperidine-1-carboxylate 4- [ Thiazol-5-ylmethyl 2- (4-fluorophenoxy) ethyl] piperidine-1-carboxylate 4- [2- (2,4-dimethylphenoxy) ethyl] thiazol-5-ylmethyl 4- [2- (2,4-dimethylphenoxy) ethyl] piperidine-1-carboxylate (4- {dimethylaminomethyl} phenoxy) ethyl] piperidine-1-carboxyl thiazol-5-ylmethyl actin and its trifluoroacetate 4- [2- (2,3-dichlorophenoxy) ethyl] piperidine-1-thiazol-5-ylmethyl 4- [2- (2,4-dichlorophenoxy) ethyl] piperidine Thiazol-5-ylmethyl-4- [2- (2,5-dichlorophenoxy) ethyl] piperidine-1-thiazol-5-ylmethyl-4- [2- (3,5-dichlorophenoxy) ethyl] piperidine-1-carboxylate Thiazol-5-ylmethyl-1- [2- (4-cyclopentylphenoxy) ethyl] piperidine-1-thiazol-5-ylmethyl-4- [2- (naphth-2-yloxy) ethyl] piperidine-1-carboxylate thiazol-5-ylmethyl 4- [2- (naphth-1-yloxy) ethyl] piperidine-1-thiazol-5-ylmethyl 4- [2- (2-methylquinolin-8-yloxy) ethyl] piperidine-carboxylate Thiazol-5-ylmethyl 4- [2- (2- {benzoxazol-2-yl} phenoxy) ethyl] piperidine-1-thiazol-5-ylmethyl -1-carboxylate 4- [2- (4- thiazol-5-ylmethyl {benzyloxy} phenoxy) ethyl] thiazol-5-ylmethyl 4- [2- (4-sulfamoylphenoxy) ethyl] piperidine-1-carboxylate 4- [2- (isoquinolin-5) thiazol-5-ylmethyl-piperidine-1-carboxylate 4- [2- (4- {carb thiazol-5-ylmethyl 4- [2- (quinolin-7-yloxy) ethyl] piperidine-1-thiazol-5-ylmethyl 4- [2- (methoxyamoyl) -phenoxy) -ethyl] -piperidine-1-carboxylate 4- [2- ( thiazol-5-ylmethyl 4- [2- (quinolin-8-yloxy) ethyl] thiazol-5-ylmethyl 4- [2- (quinolin-6-yloxy) ethyl] -piperidine-1-carboxylate 4- [2- ( Thiazol-5-ylmethyl 3- {dimethylamino} phenoxy) ethyl] piperidine-1-carboxylate and its trifluoroacetate thiazol-5-ylmethyl 4- [2- (4-cyano-3-fluorophenoxy) ethyl] piperidine-1-carboxylate Thiazol-5-ylmethyl 4- [2- (biphenyl-2-yloxy) ethyl] piperidine-1-carboxylate 4- [2- (biphenyl-3-yloxy) ethyl] piperidine-1-thiazol-5-ylmethyl 4- carboxylate Thiazol-5-ylmethyl 4- [2- (3- {trifluoromethyl} phenoxy) ethyl] piperidine-1-carboxylate 4- [2- (4-benzylphenoxy) ethyl] piperidine-1-thiazol-5-ylmethyl 4- [2- Thiazol-5-ylmethyl 4- [2- (2-cyclopentylphenoxy) ethyl] piperidine-1-carboxylate thiazol-5-ylmethyl (2-ethoxyphenoxy) ethyl] piperidine-1-carboxylate 4- {2- [4- ( 1-methyl-1-phenylethyl) phenoxy] ethyl} piperidin thiazol-5-ylmethyl 4- [2- (4-phenoxyphenoxy) ethyl] piperidine-1-thiazol-5-ylmethyl α-1-carboxylate 4- [2- (2-bromo-4-fluorophenoxy) ethyl] thiazol-5-ylmethyl 4- [2- (4- {pyrrol-1-yl} phenoxy) ethyl] thiazol-5-ylmethyl piperidine-1-carboxylate 4- [2- (3 thiazol-5-ylmethyl 4- [2- (3,5-di {tert-butyl} phenoxy) ethyl] thiazol-5-ylmethyl 4- [2- (3,5-di {tert-butyl} phenoxy) ethyl] piperidine-1-carboxylate Thiazol-5-ylmethyl 2- (2-benzylphenoxy) ethyl] piperidine-1-carboxylate 4- [2- (2- {benzyloxy} phenoxy) ethyl] thiazol-5-ylmethyl 4- [2-carboxylate] - thiazol-5-ylmethyl 4- [2- (3- {methoxycarbonyl} naphth-2-yloxy) ethyl] piperidine-1-carboxythiazol-5-yl] -piperidine-1-carboxyate Thiazol-5-ylmethyl 4- [2- (3-phenoxyphenoxy) ethyl] piperidine-1-carboxylate thiazol-5-ylmethyl 4- [2- (4-chloro-2-cyanophenoxy) ethyl] piperidine-1-carboxylate Thiazol-5-ylmethyl 4- [2- (isoquinolin-7-yloxy) ethyl] piperidine-1-carboxylate 5-ylmethyl 4 - Thiazol-5-ylmethyl 4- [2- (4- {hexyloxy} phenoxy) ethyl] piperidine-1-carboxylate thiazol-5-ylmethyl 4- [2- (3-butoxyphenoxy) ethyl] piperidine-1-carboxylate Thiazol-5-ylmethyl 4- [2- (2-methylbenzothiazol-5-yloxy) ethyl] piperidine-1-carboxylate 2- (4-chloro-5-isopropyl-2-methylphenoxy) ethyl] piperidine-1-carboxylate thiazol-5-ylmethyl 4- [2- (3- {pentafluoroethyl} phenoxy) ethyl] piperidine-1-thiazol-5-ylmethyl 4- [2- (quinolin-5-yloxy) ethyl] piperidine-1-carboxylate thiazol-5-ylmethyl 4- [2- (5-bromo-2-chlorophenoxy) ethyl] piperidine-1-thiazoyl-5-ylmethyl 4- [2- (4- {difluoromethoxy} phenoxy) -carboxylate thiazol-5-ylmethyl 4- [2- (4'-cyanobiphenyl-3-yloxy) ethyl] thiazol-5-ylmethyl] piperidine-1-carboxylate 4- [2- (6 thiazol-5-ylmethyl-piperidine-1-carboxylate-thiazol-5-ylmethyl-4- [2- (4- {thiazol-2-yl} -phenoxy) -ethyl] -piperidine-1-thiazol-5-ylmethyl-carboxylate Thiazol-5-ylmethyl 4- [2- (7-methoxynaphth-2-yloxy) ethyl] piperidine-1-carboxylate 4- [2- (4-clo thiazol-5-ylmethyl 4- [2- (2-carbamoyl-4-chlorophenoxy) ethyl] piperidine-1-carboxylate thiazol-5-yl} phenoxy) ethyl] piperidine-1-carboxylate azol-5-ylmethyl 4- [2- (5- {acetylamino} naphth-2-yloxy) ethyl] piperidin-1-carboxylate thiazol-5-ylmethyl 4- [2- (4'-cyanobiphenyl-4- thiazol-5-ylmethyl 4- [2- (4- {methanesulfonyl} phenoxy) ethyl] piperidine-1-carboxythiazol-5-ylmethyl 4- [2- (5 thiazol-5-methyl-4- [2- (1H-indol-6-yloxy) ethyl] piperidine-1-carboxylic acid thiazol-5-ylmethyl-4-ylmethyl-4- Thiazol-5-ylmethyl {2- [4-fluoro-2- (1H-pyrazol-3-yl) phenoxy] ethyl} thiazol-5-ylmethyl piperidin-1-carboxylate 4- [2- (4-cyano-2-fluorophenoxy) ethyl] thiazol-5-ylmethyl piperidin-1-carboxylate 4- [2- (2-isopropyl-5-methylphenoxy) ethyl] thiazol-5-ylmethyl piperidin-1-carboxylate 4- [2- (2- {morpholin Thiazol-5-ylmethyl-4-yl} phenoxy) ethyl] piperidin-1-carboxylate and its trifluoroacetate 4- [2- (2-methylquinolin-6-yloxy) ethyl] piperidyl thiazol-5-ylmethyl 4- {2- [4- (2-oxopyrrolidin-1-yl) phenoxy] ethyl} piperidine-1-carboxylate thiazol-5-ylmethyl 4- [2- (3 - thiazol-5-ylmethyl (R) -3- (naphth-2-yloxymethyl) pyrrolidine-1-carboxylate thiazol-2-ylmethyl (enantiomer I) - {tetrazol-1-yl} phenoxy) ethyl] piperidine-1-carboxylate ) Thiazol-2-ylmethyl (enantiomer II) -3- (naphth-2-yloxymethyl) pyrrolidine-1-carboxylate (enantiomer II) (+/-) -3- (5-chloronaph-2-yloxymethyl) pyrrolidine-1-one thiazol-2-ylmethyl (+/-) -3- (4'-fluorobiphenyl-4-yloxymethyl) pyrrolidin-1-thiazol-2-ylmethyl 4- [2- (4-fluorophenoxy) ethyl] carboxylate carboxylate] 3-carbamoylisoxazol-5-ylmethyl (-) - (R) -3 piperidine-1-carboxylate 4- [2- (4- {trifluoromethoxy} phenoxy) ethyl] 3-carbamoylisoxazol-5-ylmethyl piperidine-1-carboxylate - 3-Carbamoylisoxazol-5-ylmethyl (enantiomer I) (+/-) -3- (6-methoxynaphth-2-yloxymethyl) pyrrolidine-1-carboxylate (naphth-2-yloxymethyl) pyrrolidine-1-carboxylate carbamoylisoxazol-5-ylmethyl (+) - (S) -3- (naphth-2-yloxymethyl) pyrrolidine-1 3-carbamoylisoxazol-5-ylmethyl-carboxylate (enantiomer II). A compound according to any one of the preceding claims, characterized in that the compound is of formula (II): wherein R 1, A, R 4, n and m are as defined in one of the preceding claims; in the form of the base or an addition salt with an acid. A compound according to any one of the preceding claims, characterized in that the compound is of formula (III): wherein R 1, A are neither as defined in one of claims 1 to 9; in the form of the base or an addition salt with an acid. A process for the preparation of a compound as defined in any one of claims 1 to 10, comprising the stage of reaction of an amine derivative, a compound of the following general formula (II): R 1, R 2, A, nor are as defined in one of the preceding claims, with a carbonate of the following general formula (III): wherein Z represents a hydrogen atom or a nitro group and R 3 and R 4 are as defined in one of the preceding claims, in the presence of a base such as triethylamine, pyridine, N, N-dimethylaminopyridine or Î ±, β-diisopropylethylamine in an organic solvent such as toluene, acetonitrile or dichloroethane at a temperature between room temperature and the refluxing temperature of the solvent. A compound according to any one of claims 1 to 10, in the form of a base or an addition salt with a pharmaceutically acceptable acid, for use as a medicament. Pharmaceutical composition comprising at least one compound as defined in any one of claims 1 to 10, in the form of the base or an addition salt with a pharmaceutically acceptable acid, and optionally one or more pharmaceutically acceptable excipients. A compound according to any one of claims 1 to 10 in the form of the base or a pharmaceutically acceptable acid addition salt for use in the preparation of a medicament for preventing or treating a condition wherein endogenous cannabinoids and / or any other substrate metabolised by the FAAH enzyme are involved. A compound according to any one of claims 1 to 10, in the form of the base or a pharmaceutically acceptable acid addition salt, for use in the preparation of a medicament for preventing or treating acute or chronic pain of the neurogenic type, acute or chronic pain associated with inflammatory diseases, acute or chronic peripheral pain, dizziness, vomiting, nausea, eating disorders, neurological and psychiatric disorders, acute or chronic neurodegenerative disorders, epilepsy, sleep disorders, cardiovascular disease, renal ischemia , cancers, immune system disorders, allergic diseases, parasitic, viral or bacterial infectious diseases, inflammatory diseases, osteoporosis, eye conditions, lung conditions, gastrointestinal disorders, urinary incontinence or bladder inflammation.