Tetrahydropyridyl-alkyl-heterocycles, method for preparing the same and pharmaceutical compositions containing the same

1. A compound of formula (I):

in which

X represents N or CH;

R 1 represents a hydrogen or halogen atom or a CF 3 group;

R 2 and R 3 independently represent a hydrogen atom or a methyl group;

n is 0 or 1;

A represents a nitrogenous heterocycle of formula (a)–(i) and: (l):

 where R 4 , R 5 and R 6 each independently represent a hydrogen atom or a (C 1 –C 4 )alkyl group;

the dotted line with a solid line represent single or double bond;

R 7 and R 8 each independently represent a hydrogen or halogen atom or a (C 1 –C 4 )alkyl or (C 1 –C 4 )alkoxy group; or

an N-oxide, salt or solvates, thereof;

provided that, when X is CH, then A is not an indol-4-yl moiety of formula (a).

2. The compound according to claim 1 , where n is zero.

3. The compound according to claim 1 , where R 2 and R 3 are each a hydrogen.

4. The compound according to claim 1 , where R 1 is a CF 3 group.

5. The compound as claimed in claim 1 , where X is CH and R 1 is in the 3-position of the benzene.

6. The compound according to claim 1 , where X is CH and R 1 is in the 2-position of the benzene.

7. The compound according to claim 1 , where X is N and the pyridine is substituted in the 2,6-positions.

8. The compound according to claim 1 , where R 4 , R 5 and R 6 each independently represent a hydrogen atom or a (C 1 –C 4 )alkyl group.

9. The compound according to claim 1 , where A is the nitrogenous heterocycle of formula (a).

10. The compound according to claim 1 , where R 7 and R 8 each independently represent a hydrogen atom or a (C 1 –C 4 )alkyl group.

11. The compound according to claim 1 , where A is is the nitrogenous heterocycle of formula (i).

12. The compound according to any one of claims 1 to 11 , in the form of its N-oxide derivatives.

13. The compound according to claim 1 , chosen from,

5-[2-(4-(3-(Trifluoromethyl)phenyl)-1,2,3,6-tetrahydro-pyrid-1-yl)ethyl]-1H-indole;

6-[2-(4-(3-(Trifluoromethyl)phenyl)-1,2,3,6-tetrahydro-pyrid-1-yl)ethyl]-1H-indole;

6-[2-(4-(3-(Trifluoromethyl)phenyl)-1,2,3,6-tetrahydro-pyrid-1-yl)ethyl]-1H-benzimidazole;

7-[2-(4-(3-(Trifluoromethyl)phenyl)-1,2,3,6-tetrahydro-pyrid-1-yl)ethyl]-N-methyl-1,2,3,4-tetrahydroisoquinoline;

7-[2-(4-(3-(Trifluoromethyl)phenyl)-1,2,3,6-tetrahydro-pyrid-1-yl)ethyl]-1,2,3,4-tetrahydroisoquinoline;

6-[2-(4-(3-(Trifluoromethyl)phenyl)-1,2,3,6-tetrahydro-pyrid-1-yl)ethyl]-4-methoxyquinazoline;

6-[2-[4-(3-(Trifluoromethyl)phenyl)-1,2,3,6-tetrahydro-pyrid-1-yl]ethyl]quinoxaline;

6-[2-[4-(3-(Trifluoromethyl)phenyl)-1,2,3,6-tetrahydro-pyrid-1-yl]ethyl]-2,3-dimethylquinoxaline;

6-[2-[4-(3-(Trifluoromethyl)phenyl)-1,2,3,6-tetrahydro-pyrid-1-yl]ethyl]-2,3-diethylquinoxaline;

6-[2-[4-(6-(Trifluoromethyl)pyrid-2-yl)-1,2,3,6-tetrahydro-pyrid-1-yl]ethyl]quinoxaline; and

6-[2-[4-(3-(Trifluoromethyl)phenyl)-1,2,3,6-tetrahydro-pyrid-1-yl]ethyl]phthalazine; or

the N-oxide, salt or solvate thereof.

14. A process for the preparation of a compound of formula (I) according to claim 1 , which comprises the reaction of a compound of formula (II)

with a compound of formula (III):

in which R 1 , X, R 2 , R 3 , n and A are as defined in claim 1 and L is a leaving group, isolation of the compound of formula (I) and optional conversion to one of its salts or solvates or to its N-oxide derivatives.

15. A pharmaceutical composition, comprising, as active principle, a compound according to claim 1 together with a pharmaceutically acceptable carrier.

16. The composition according to claim 15 , which comprises from 0.001 to 100 mg of active principle.

17. A pharmaceutical composition, comprising, as active principle, a compound according to claim 13 together with a pharmaceutically acceptable carrier.

18. A method of producing analgesia in a patient in need thereof which comprises administering to said patient an analgesically effective amount of a compound according to claim 13 .

19. A method for the treatment of a disease related to pain, osteoarthritis or rheumatoid arthritis which comprises administering to a patient in need of such treatment an effective amount of a compound of formula (I)

in which

X represents N or CH;

R 1 represents a hydrogen or halogen atom or a CF 3 group;

R 2 and R 3 independently represent a hydrogen atom or a methyl group;

n is 0 or 1;

A represents a nitrogenous heterocycle of formula (a)–(i) and (l):

 where R 4 , R 5 and R 6 each independently represent a hydrogen atom or a (C 1 –C 4 )alkyl group;

the dotted line with a solid line represent a single or double bond;

R 7 and R 8 each independently represent a hydrogen or halogen atom or a (C 1 –C 4 )alkyl or (C 1 –C 4 )alkyl group;

or an N-oxide or pharmaceutically acceptable salt or solvate thereof; provided that, when X is CH, then A is not an indol-4-yl moiety of formula (a).

20. A method for the treatment of a disease related to pain, osteoarthritis or rheumatoid arthritis which comprises administering to a patient in need of such treatment an effective amount of a compound according to claim 13 .