3-arylindole derivatives and their use as CB

1. A compound of formula:

in which:

Ar represents:

a) a phenyl mono-, di- or trisubstituted by one or more groups chosen from: a halogen atom, a (C 1 –C 4 )alkyl, a trifluoromethyl, an amino, a nitro, a hydroxyl, a (C 1 –C 4 )alkoxy, a (C 1 –C 4 )alkylsulphanyl or a (C 1 –C 4 )alkylsulphonyl;

b) a naphthyl which is unsubstituted or substituted once or twice by a halogen atom, a (C 1 –C 4 )alkyl or a trifluoromethyl;

A represents a C 2 –C 6 alkylene radical;

Y represents a group chosen from SR 4 , SOR 4 , SO 2 R 4 , SO 2 NR 5 R 6 , N(R 7 )SO 2 R 4 , OR 4 or NR 7 SO 2 NR 5 R 6 ;

R 1 , R 3 and R′ 3 represent, each independently of one another, hydrogen, a hydroxyl, a halogen atom, a (C 1 –C 4 )alkyl, a trifluoromethyl or a (C 1 –C 4 )alkoxy;

R 2 represents hydrogen or a (C 1 –C 4 )alkyl;

R 4 represents a (C 1 –C 4 )alkyl or a trifluoromethyl;

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

R 7 represents hydrogen or a (C 1 –C 4 )alkyl;

and its optional salts and/or its solvates.

2. A compound according to claim 1 of formula:

in which:

Ar represents:

a) a phenyl mono-, di- or trisubstituted by one or more groups chosen from: a halogen atom, a (C 1 –C 4 )alkyl, a trifluoromethyl, an amino, a nitro, a (C 1 –C 4 )alkoxy, a (C 1 –C 4 )alkylsulphanyl or a (C 1 –C 4 )alkylsulphonyl;

b) a naphthyl which is unsubstituted or substituted once or twice by a halogen atom, a (C 1 –C 4 )alkyl or a trifluoromethyl;

n represents 2, 3 or 4;

Y represents a group chosen from SR 4 , SOR 4 , SO 2 R 4 , SO 2 NR 5 R 6 , N(R 7 )SO 2 R 4 or OR 4 ;

R 1 represents a halogen atom, a (C 1 –C 4 )alkyl, a trifluoromethyl or a (C 1 –C 4 )alkoxy;

R 2 represents hydrogen or a (C 1 –C 4 )alkyl;

R 3 represents hydrogen, a (C 1 –C 4 )alkyl or a halogen;

R 4 represents a (C 1 –C 4 )alkyl;

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

R 7 represents hydrogen or a (C 1 –C 4 )alkyl;

and its optional salts and/or its solvates.

3. A compound according to claim 1 of formula (I) in which R 1 is in the 7 position of the indole nucleus and represents a methyl or a chlorine or bromine atom.

4. A compound according to claim 1 of formula (I) in which R 2 represents a (C 1 –C 4 )alkyl.

5. A compound according to claim 1 of formula (I) in which R 3 is hydrogen or R 3 is in the 6 position of the indole nucleus and represents either a chlorine atom or a methyl.

6. A compound according to claim 1 of formula (I) in which R′ 3 is hydrogen.

7. A compound according to claim 1 of formula (I) in which Ar represents a phenyl mono- or disubstituted by a halogen atom, a methyl, a trifluoromethyl, a methoxy, a methylsulphanyl or a methylsulphonyl.

8. A compound according to claim 1 of formula (I) in which Y represents SO 2 R 4 or NHSO 2 R 4 .

9. A compound according to claim 1 of formula (I) in which:

Ar represents a phenyl mono- or disubstituted by a halogen atom, a methyl, a trifluoromethyl, a methoxy, a methylsulphanyl or a methylsulphonyl;

A represents a (CH 2 ) n group;

n represents 2, 3 or 4;

Y represents SO 2 R 4 or NHSO 2 R 4 ;

R 1 represents a methyl or a chlorine or bromine atom in the 7 position of the indole nucleus;

R 2 represents a methyl;

R 3 is hydrogen or R 3 represents either a chlorine atom or a methyl in the 6 position of the indole nucleus;

R′ 3 is hydrogen;

R 4 represents a methyl or an ethyl;

and its optional salts and/or its solvates.

10. Process for the preparation of a compound of formula (I) according to claim 1 , of its optional salts and/or its solvates wherein:

a) an indole of formula:

in which R 1 , R 2 , R 3 and R′ 3 are as defined in claim 1 for a compound of formula (I), is treated with a methylmagnesium halide and with an acid halide of formula ArCOHal (III), in which Ar is as defined for the compound of formula (I) and Hal represents a halogen atom;

b) the compound thus obtained, of formula:

is treated with a halide of formula Hal—A—Y (V), in which —A— and Y are as defined for a compound of formula (I) in claim 1 and Hal represents a halogen atom, in the presence of a base.

11. Process according to claim 10 wherein stage b) is modified in the following way:

b1) the compound obtained in stage a), of formula:

 is treated with a compound of formula Z—A—Cl (VI), in which Z represents either a hydroxyl group or a halogen atom;

b2) optionally, the compound thus obtained, of formula:

 is treated with sodium iodide;

b3) the compound thus obtained in stage b1, of formula (VII), or in stage b2), of formula:

 is treated with a Y {circle around (−)} anion.

12. Process according to claim 10 for preparing a compound of formula (I) in which Y represents an SOR 4 group or an SO 2 R 4 group, from a compound of formula (I) in which Y represents an SR 4 group wherein the following additional stage is carried out:

c1) the compound obtained, of formula:

 is treated with an oxidizing agent.

13. Process according to claim 10 for preparing a compound of formula (I) in which Y represents an N(R 7 ) SO 2 R 4 group with R 7 other than H, from a compound of formula (I) in which Y represents an NHSO 2 R 4 group wherein the following additional stage is carried out:

c2) the compound obtained, of formula:

 is treated with an alkylating agent in the presence of a base.

14. Process according to claim 10 for preparing a compound of formula (I) in which Y represents an SO 2 NR 5 R 6 group from a compound of formula (I) in which Y represents an SO 2 NHR 5 group wherein the following additional stage is carried out:

c3) the compound obtained, of formula:

 is treated with an alkylating agent in the presence of a base.

15. Process according to claim 10 for preparing a compound of formula (I) in which Y represents an NR 7 SO 2 R 4 group or an NR 7 SO 2 NR 5 R 6 group wherein:

b4) the compound of formula:

 is converted into a compound of formula:

c4) treatment is carried out with a halide of formula HalSO 2 R 4 or respectively HalSO 2 NR 5 R 6 .

16. Process for the preparation of a compound of formula (I) according to claim 1 , of its salts and/or solvates wherein:

i) an indole of formula:

 in which R 1 , R 2 , R 3 and R′ 3 are as defined for the compound of formula (I), is treated with a halide of formula Hal—A—Y (V) in which —A— and Y are as defined for a compound of formula (I) in claim 1 and Hal represents a halogen atom in the presence of a base;

ii) the compound thus obtained, of formula:

 is treated with an acid halide of formula ArCOHal (III) and Hal is a halogen atom.

17. Process according to claim 16 wherein:

i1) an indole of formula:

 is treated with a compound of formula Z—A—Cl (VI) and Z represents a hydroxyl group or a halogen atom;

i2) optionally, the compound thus obtained, of formula:

 is treated with sodium iodide;

i3) the compound thus obtained in stage i1) or in stage i2), of formula:

 is treated with an anion of formula Y − ;

ii) the compound thus obtained, of formula:

 is treated with an acid halide of formula ArCOHal (III) and Hal is a halogen atom.

18. Pharmaceutical composition comprising, as active principle, a compound according to claim 1 together with at least one pharmaceutical excipient.

19. Pharmaceutical composition according to claim 18 comprising from 0.1 to 1000 mg of active principle in the form of a dosage unit in which the active principle is mixed with at least one pharmaceutical excipient.

20. A process according to claim 16 wherein Hal represents bromine.

21. Pharmaceutical composition comprising, as active principle, a compound according to claim 2 together with at least one pharmaceutical excipient.

22. Pharmaceutical composition comprising, as active principle, a compound according to claim 3 together with at least one pharmaceutical excipient.

23. Pharmaceutical composition comprising, as active principle, a compound according to claim 4 together with at least one pharmaceutical excipient.

24. Pharmaceutical composition comprising, as active principle, a compound according to claim 5 together with at least one pharmaceutical excipient.

25. Pharmaceutical composition comprising, as active principle, a compound according to claim 6 together with at least one pharmaceutical excipient.

26. Pharmaceutical composition comprising, as active principle, a compound according to claim 7 together with at least one pharmaceutical excipient.

27. Pharmaceutical composition comprising, as active principle, a compound according to claim 8 together with at least one pharmaceutical excipient.

28. Pharmaceutical composition comprising, as active principle, a compound according to claim 9 together with at least one pharmaceutical excipient.

29. N-[3-(6,7-Dichloro-3-[2-fluoro-3-(trifluoromethyl)benzoyl]-2-methyl-1H-indol-1-yl)propyl]methanesulphonamide according to claim 9 .

30. Pharmaceutical composition comprising as active principle, a compound according to claim 29 together with at least one pharmaceutical excipient.