N-[Phenyl(piperidin-2-yl)methyl]benzamide derivatives, their preparation and their application in therapy

1. A compound in the form of an enantiomer (1R,2R) or (1S,2S) or in the form of a threo diastereoisomer, corresponding to general formula (I)

in which A represents

a group of general formula N—R 1 , a group of general formula N + (O − )R 1 or a group of general formula N + (R′)R 1 , and in which R 1 represents either a hydrogen atom, or a linear or branched (C 1 –C 7 )alkyl group optionally substituted with one or more fluorine atoms, or a (C 4 –C 7 )cycloalkyl group, or a (C 3 –C 7 )cycloalkyl(C 1 –C 3 )alkyl group, or a phenyl(C 1 –C 3 )alkyl group optionally substituted with one or two hydroxyl or methoxy groups, or a (C 2 –C 4 )alkenyl group, or a (C 2 –C 4 )alkynyl group,

R′ represents a linear or branched (C 1 –C 7 )alkyl group,

X represents a hydrogen atom or one or more substituents chosen from halogen atoms and trifluoromethyl, linear or branched (C 1 –C 4 )alkyl and (C 1 –C 4 )alkoxy groups,

R 2 represents either a hydrogen atom, or one or more substituents chosen from halogen atoms and trifluoromethyl, (C 1 –C 4 )alkyl or (C 1 –C 4 )alkoxy groups, or amino groups of general formula NR 3 R 4 in which R 3 and R 4 each represent, independently of each other, a hydrogen atom or a (C 1 –C 4 )alkyl group, or form with the nitrogen atom carrying them a pyrrolidine, piperidine or morpholine ring, or a phenyl group optionally substituted with an atom or a group as defined for the symbol X above,

in the form of a free base or of an addition salt with an acid.

2. A compound according to claim 1 wherein it has the configuration (1S,2S) and in that R 2 represents one or more halogen atoms or trifluoromethyl groups.

3. A compound according to claim 1 wherein it has the configuration (1R,2R) and in that R 2 represents a halogen atom and an amino group of general formula NR 3 R 4 as defined in claim 1 .

4. A compound according to claim 1 wherein A represents a group of general formula N—R 1 in which R 1 represents either a hydrogen atom, or a linear or branched (C 1 –C 7 )alkyl group optionally substituted with one or more fluorine atoms and said compound in the form of a free base or of an addition salt with an acid.

5. A compound according to claim 1 which is selected from the group consisting of:

threo-2-chloro-N-[(1-ethylpiperidin-2-yl)phenylmethyl]-3-trifluoromethylbenzamide hydrochloride;

threo-2-chloro-N-[(1-ethylpiperidin-2-yl)phenylmethyl]-3-trifluoromethylbenzamide;

2-chloro-N-[(1S)-[(2S)-1-methylpiperidin-2-yl]phenylmethyl]-3-trifluoromethyl -benzamide hydrochloride;

2-chloro-N-[(1S)-[(2S)-1-methylpiperidin-2-yl]phenylmethyl]-3-trifluoromethyl-benzamide;

threo-4-amino-3-chloro-N-[(1-methylpiperidin-2-yl)phenylmethyl]-5-trifluoromethyl-benzamide hydrochloride;

threo-4-amino-3-chloro-N-[(1-methylpiperidin-2-yl)phenylmethyl]-5-trifluoromethyl-benzamide;

4-amino-3-chloro-N-[(1R)-[(2R)-1-methylpiperidin-2-yl]phenylmethyl]-5-trifluoro -methylbenzamide hydrochloride;

4-amino-3-chloro-N-[(1R)-[(2R)-1-methylpiperidin-2-yl]phenylmethyl]-5-trifluoro -methylbenzamide;

threo-2-chloro-N-[phenyl(piperidin-2-yl)methyl]-3-trifluoromethylbenzamide hydrochloride;

threo-2-chloro-N-[phenyl(piperidin-2-yl)methyl]-3-trifluoromethylbenzamide;

2-chloro-N-[(S)-phenyl-[(2S)-piperidin-2-yl]methyl]-3-(trifluoromethyl)benzamide hydrochloride;

2-chloro-N-[(S)-phenyl-[(2S)-piperidin-2-yl]methyl]-3-(trifluoromethyl)benzamide;

2-chloro-N-[[1-methyl-1-oxido-piperidin-2-yl](phenyl)methyl]-3-trifluoromethyl -benzamide; and

2(S)-2[(1S)-[[2-chloro-3-(trifluoromethyl)benzoyl]amino](phenyl)methyl]-1,1-dimethylpiperidinium iodide or

a pharmaceutically acceptable salt thereof.

6. 2-Chloro-N-[(S)-phenyl-[(2S)-piperidin-2-yl]methyl]-3-(trifluoromethyl)benzamide according to claim 1 .

7. 2-Chloro-N-[(S)-phenyl-[(2S)-piperidin-2-yl]methyl]-3-(trifluoromethyl)benzamide hydrochloride 1:1 according to claim 6 .

8. 2-chloro-N-[(1S)-[(2S)-1-methylpiperidin-2-yl]phenylmethyl]-3-trifluoromethylbenzamide according to claim 1 .

9. 2-chloro-N-[(1S)-[(2S)-1-methylpiperidin-2-yl]phenylmethyl]-3-trifluoromethylbenzamide hydrochloride 1:1 according to claim 1 .

10. 4-amino-3-chloro-N-[(1R)-[(2R)-1-methylpiperidin-2-yl]phenylmethyl]-5-trifluoromethylbenzamide hydrochloride 1:1 according to claim 1 .

11. A Pharmaceutical composition comprising a compound according to claim 1 combined with an excipient.

12. A pharmaceutical composition comprising a compound according to claim 2 combined with an excipient.

13. A pharmaceutical composition comprising a compound according to claim 3 combined with an excipient.

14. A pharmaceutical composition comprising a compound according to claim 6 combined with an excipient.

15. A pharmaceutical composition comprising a compound according to claim 7 combined with an excipient.

16. A pharmaceutical composition comprising a compound according to claim 5 combined with an excipient.

17. A pharmaceutical composition comprising a compound according to claim 8 combined with an excipient.

18. A pharmaceutical composition comprising a compound according to claim 9 combined with an excipient.

19. A pharmaceutical composition comprising a compound according to claim 10 combined with an excipient.