Patent EA-004102-B1 (EA)
Title: Pyridine compounds, a process for their preparation and pharmaceutical compositions containing them
Inventor: PEGLION JEAN-LOUIS
IPC: A61K31/4365
Filed: 2000-08-25
Abstract: 1. Compounds of formula (I): wherein: W represents: - either a naphthyl group optionally substituted by one or more identical or different groups selected from halogen, linear or branched (C1-C6)alkyl, hydroxy, linear or branched (C1-C6)alkoxy, cyano, nitro, linear or branched trihalo(C1-C6)alkyl, methylenedioxy and ethylenedioxy, - or a group of formula Y where : wherein E, together with the carbon atoms of the phenyl ring to which it is bonded, represents a group selected from naphthyl, 2,3-dihydro-1,4-benzodioxinyl, chromanyl, 2H-chromenyl, isochromanyl, 2,3-dihydrobenzofaranyl, benzofuranyl, indolyl, 1,3-dihydro-2H-benzimidazol-2-one and 1,3-benzoxazol-2-one and each of the said Y groups to be optionally substituted by one or more identical or different groups selected from halogen, hydroxy, cyano, nitro, linear or branched (C1-C6)alkyl, linear or branched (C1-C6)alkoxy, linear or branched trihalo(C1-C6)alkyl, heterocycloalkylalkylene, which is the 1,2,4-triazol-1-ylmethyl group, the imidazol-1-ylmethyl group or the 1H-imidazol-5-ylmethyl group or oxo groups, provided that in that case the group Y can be substituted only by a single oxo group and that E, together with the carbon atoms of the phenyl ring to which it is bonded, represents then a monocyclic ring having 5 ring members and containing two identical or different hetero atoms selected from oxygen and nitrogen, n represents an integer from 1 to 6 inclusive, Z represents a single bond, an oxygen atom, or a nitrogen atom substituted by a group selected from hydrogen, linear or branched (C1-C6)alkyl (itself optionally substituted by one or more hydroxy groups) and aryl-(C1-C6)alkyl in which the alkyl moiety may be linear or branched, A represents a CH group or a nitrogen atom, Q represents a CH group or a nitrogen atom, it being understood that at least one of the groups A and Q represents a nitrogen atom, and that A represents a nitrogen atom when Z represents a single bond, and M, together with the carbon atoms of the pyridine ring to which it is bonded, represents a thieno, furo, pyrrolo or oxopyrrolo group, their isomers, and addition salts thereof with a pharmaceutically acceptable acid or base. 2. Compounds according to claim 1, characterised in that W represents a group selected from naphthyl, 2,3-dihydro-1,4-benzodioxinyl, chromanyl, 2H-chromenyl, isochromanyl, 2,3-dihydrobenzofaranyl, benzofuranyl, indolyl, 1,3-dihydro-2H-benzimidazol-2-one and 1,3-benzoxazol-2-one, their isomers, and also addition salts thereof with a pharmaceutically acceptable acid or base. 3. Compounds according to claim 1, characterised in that when W is substituted by a heterocycloalkylalkylene group selected from the 1,2,4-triazol-1-ylmethyl group, the imidazol-1-ylmethyl group and the 1H-imidazol-5-ylmethyl group, their isomers, and also addition salts thereof with a pharmaceutically acceptable acid or base. 4. Compounds according to either claim 1 or claim 2, characterised in that W represents a group selected from 1-naphthyl, isochroman-1-yl and 2,3-dihydrobenzo-furan-5-yl, their isomers, and also addition salts thereof with a pharmaceutically acceptable acid or base. 5. Compounds according to any one of claims 1 to 3, characterised in that W represents a group selected from 5-(1,2,4-triazol-ylmethyl)-1H-indol-3-yl, 5-(imidazol-1-ylmethyl)-1H-indol-3-yl and 5-(1H-imidazol-5-ylmethyl)-1H-indol-3-yl, their isomers, and also addition salts thereof with a pharmaceutically acceptable acid or base. 6. Compounds according to either claim 1 or claim 2, characterised in that W represents a group selected from 1,3-benzoxazol-2-one-1-yl and 1,3-dihydro-2H-benzimidazol-2-one-1-yl, their isomers, and also addition salts thereof with a pharmaceutically acceptable acid or base. 7. Compounds according to claim 1, characterised in that Z represents a single bond, their isomers, and also addition salts thereof with a pharmaceutically acceptable acid or base. 8. Compounds according to claim 1, characterised in that, when A represents a CH group, Q represents a nitrogen atom, n is 1 and W represents a 2-naphthyl group, Z represents a nitrogen atom substituted by a group selected from hydrogen, methyl and hydroxyethylene, their isomers, and also addition salts thereof with a pharmaceutically acceptable acid or base. 9. Compounds according to claim 1, characterised in that n represents 2 or 3, their isomers, and also addition salts thereof with a pharmaceutically acceptable acid or base. 10. Compounds according to claim 1, characterised in that M, together with the carbon atoms of the pyridine ring to which it is bonded, represents a thienyl or furyl group, their isomers, and also addition salts thereof with a pharmaceutically acceptable acid or base. 11. Compound according to claim 1 that is 4-{l-[2-(1-naphthyl)ethyl]-4-piperidinyl}thieno[3,2-c]pyridine, its isomers, and also addition salts thereof with a pharmaceutically acceptable acid or base. 12. Compound according to claim 1 that is 4-{l-[2-(1-naphthyl)ethyl]-4-piperidinyl}furo[3,2-c]pyridine, its isomers, and also addition salts thereof with a pharmaceutically acceptable acid or base. 13. Compound according to claim 1 that is 4-{4-[2-(2,3-dihydrobenzofuran-5-yl)ethyl]-1-piperazinyl}furo[3,2-c]pyridine, its isomers, and also addition salts thereof with a pharmaceutically acceptable acid or base. 14. Compound according to claim 1 that is 4-{4-[2-(isochroman-1-yl)ethyl]-1-piperazinyl}thieno[3,2-c]pyridine, its isomers, and also addition salts thereof with a pharmaceutically acceptable acid or base. 15. Compounds according to claim 1 that are 4-(4-{2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethyl}-1-piperazinyl)furo[3,2-c]pyridine and 4-(4-{2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethyl}-1-piperazinyl)-1H-pyrrolo [3,2-c]pyridine, their isomers, and also addition salts thereof with a pharmaceutically acceptable acid or base. 16. Compounds according to claim 1 that are 1-[2-(4-furo[3,2-c]pyridin-4- yl-1-piperazinyl)ethyl]-1,3-dihydro-2H-benzimidazol-2-one and 1-[2-(4-thieno[3,2-c]-pyridin-4-yl-1-piperazinyl)ethyl]-1,3-dihydro-2H-benzimidazol-2-one, their isomers, and also addition salts thereof with a pharmaceutically acceptable acid or base. 17. Pharmaceutical compositions comprising as active ingredient at least one compound of formula (I) according to any one of claims 1 to 16, alone or in combination with one or more pharmaceutically acceptable, inert, non-toxic excipients or carriers. 18. Pharmaceutical compositions according to claim 17 comprising at least one active ingredient according to any one of claims 1 to 16 for use in the treatment of depression, anxiety, panic attacks, obsessive-compulsive disorders, phobias, impulsive disorders and cognitive disorders.