Patent EA-004473-B1 (EA)
Title: Heterocycloalkylbenzocyclobutane and heteroalkylbenzocyclobutane derivatives and pharmaceutical compositions containing them
Inventor: PEGLION JEAN-LOUIS
IPC: C07D319/14
Filed: 2001-04-12
Abstract: 1. Compounds of formula (I): wherein: denotes a single bond or a double bond, n is an integer from 1 to 6 inclusive, R1 and R2 which may be identical or different, each independently of the other represent a group selected from a hydrogen atom, a linear or branched (C1-C6)alkyl group, an aryl group, an aryl-(C1-C6)alkyl group in which the alkyl moiety is linear or branched, a cycloalkyl group, a cycloalkyl-(C1-C6)alkyl group in which the alkyl moiety is linear or branched, a linear or branched (C2-C6)alkenyl group, a linear or branched (C2-C6)alkynyl group, a heterocycloalkyl group, a heterocycloalkyl-(C1-C6)alkyl group in which the alkyl moiety is linear or branched, a heteroaryl group, and a heteroaryl-(C1-C6)alkyl group in which the alkyl moiety is linear or branched, X represents a group selected from -CH=CH-, an oxygen atom, a group S(O)m wherein m is an integer from 0 to 2 inclusive, and NR3 wherein R3 represents a group selected from a hydrogen atom, a linear or branched (C1-C6)alkyl group, an aryl group, an aryl-(C1-C6)-alkyl group in which the alkyl moiety is linear or branched, a cycloalkyl group, a cycloalkyl-(C1-C6)alkyl group in which the alkyl moiety is linear or branched, a linear or branched (C2-C6)alkenyl group, and a linear or branched (C2-C6)alkynyl group, Y represents a CH or CH2; group depending on whether denotes a single bond or a double bond, or may have the additional meaning of an oxygen atom when X represents an oxygen atom, T represents a cyclopentyl or cyclohexyl their isomers and addition salts thereof with a pharmaceutically acceptable acid or base, it being understood that: x "aryl group" is understood to mean a group selected from phenyl, biphenyl, naphthyl, dihydronaphthyl, tetrahydronaphthyl, indanyl, indenyl and benzocyclobutyl, it being possible for each of those groups to be optionally substituted by one or more identical or different groups selected from halogen atoms, linear or branched (C1-C6)alkyl groups, hydroxy groups, linear or branched (C1-C6)alkoxy groups, nitro groups, cyano groups, linear or branched trihalo-(C1-C6)alkyl groups, ammo groups, monoalkylamino groups in which the alkyl moiety has from 1 to 6 carbon atoms and is linear or branched and dialkylamino groups in which each alkyl moiety has from 1 to 6 carbon atoms and is linear or branched, x "heteroaryl group" is understood to mean an aryl group as defined hereinbefore, containing within the ring system from 1 to 3 identical or different hetero atoms selected from oxygen, nitrogen and sulphur, said heteroaryl group being optionally substituted by one or more identical or different groups selected from the substituents defined above for the aryl group, x "cycloalkyl group" is understood to mean a mono- or poly-cyclic system, having from 3 to 12 ring members, optionally containing one or more unsaturations, which do not confer an aromatic character upon the said ring system, x "heterocycloalkyl group" is understood to mean a cycloalkyl group as defined hereinbefore, containing within the ring system from one to three identical or different hetero atoms selected from oxygen, nitrogen and sulphur. 2. Compounds of formula (I) according to claim 1, characterised in that n is 1, their isomers and addition salts thereof with a pharmaceutically acceptable acid or base. 3. Compounds of formula (I) according to claim 1, characterised in that R1 and R2, which may be identical or different, represent a hydrogen atom, a linear or branched (C1-C6)alkyl group, or a 2,3-dihydro-1,4-benzodioxin-2-ylmetbyl group, their isomers and addition salts thereof with a pharmaceutically acceptable acid or base. 4. Compounds of formula (I) according to any one of claims 1 to 3, characterised in that they are compounds of formula (I/A) : wherein n, R1, R2 and T are as defined for formula (I), X10 represents an oxygen atom or a sulphur atom, and Y10 represents a CH group, their isomers and addition salts thereof with a pharmaceutically acceptable acid or base. 5. Compounds of formula (I) according to any one of claims 1 to 3, characterised in that they are compounds of formula (US): wherein X, Y, n, R1, R2, R3 and T are as defined for formula (I), their isomers and addition salts thereof with a pharmaceutically acceptable acid or base. 6. Compounds of formula (I/B) according to claim 5, characterised in that n is 1, and X represents a group NR3 wherein R3 represents a hydrogen atom or a linear or branched (C1-C6)alkyl group, their isomers and addition salts thereof with a pharmaceutically acceptable acid or base. 7. Compounds of formula (I) according to any one of claims 1 to 3, characterised in that they are compounds of formula (IC): wherein n, R1, R2, X and T are as defined for formula (I) and Y20 represents a CH or CH2 group, their isomers and addition salts thereof with a pharmaceutically acceptable acid or base. 8. Compounds of formula (I) according to any one of claims 1 to 3, characterised in that they are compounds of formula (I/D) : wherein n, R1, R2, X and T are as defined for formula (I) and Y20 represents a CH or CH2 group, their isomers and addition salts thereof with a pharmaceutically acceptable acid or base. 9. Compounds of formula (I) according to any one of claims 1 to 3, characterised in that they are compounds of formula (I/E): wherein n, R1, R2, X and T are as defined for formula (I) and Y20 represents a CH or CH2 group, their isomers and addition salts thereof with a pharmaceutically acceptable acid or base. 10. Compounds of formula (I) according to any (me of claims 1 to 3, characterised in that they are compounds of formula (I/F): wherein n, R1, R2, X and Y are as defined for formula (I) and Y20 represents a CH or CH2 group, their isomers and addition salts thereof with a pharmaceutically acceptable acid or base. 11. Compounds of formula (I) according to claim 1 which are : x 1-{6-[(dimethylamino)methyl]-1-methyl-2,3,5,6-tetrahydro-1H-cyclobuta[f]indol-6-yl}cyclohexanol, x 1-{6-[(dimethylamino)methyl]-2,3,5,6-tetrahydro-1H-cyclobuta[f]indol-6-yl}cyclohexanol, x 1-{5-[(dimethylamino)methyl]-5,6-dihydrocyclobuta[f] [1]benzofuran-5-yl}cyclohexanol, x 1-{5-[(dimethylamino)methyl]-5,6-dihydrocyclobuta[f][1]benzothien-5-yl}cyclohexanol, x 1-{6-[(dimethylamino)methyl]-1-methyl-5,6-dihydro-1H-cyclobuta[f]indol-6-yl}cyclohexanol, x 1-{7-[(dimethylamino)methyl3-2,3,6,7-tetrahydro-1H-cyclobuta[e]indol-7-yl}cyclohexanol, x 1-{5-[(methylamino)methyl]-5,6-dihydrocyclobuta[f][1]benzothien-5-yl}cyclopentanol, x 1-{5-[(dimethylamino)methyl]-5,6-dihydrocyclobuta[f][1]benzothien-5-yl}cyclopentanol, x (+)-1-{5-[(dimethylamino)methyl]-5,6-dihydirocyclobuta[f] [1]benzothien-5-yl}cyclopentanol, x (-)-1-{5-[(dimethylamino)methyl]-5,6-dihydrocyclobuta[f] [1]benzothien-5-yl}cyclopentanol, x 1-{6-[(dimethylamino)methyl]-5,6-dihydrocyclobuta[f] [1]benzothien-6-yl}cyclopentanol, x 1-{5-[(dimethylamino)methyl]-1-methyl-5,6-dihydro-1H-cyclobuta[f]indol-5-yl}cyclopentanol, x 1-{7-[(dimethylamino)methyl]-6,7-dihydrocyclobuta[f] [1]benzofuran-7-yl}cyclopentanol, x 1-{1-[(dimethylamino)methyl]-1,2-dihydrocyclobuta[b]naphthalen-1-yl}cyclopentanol, x 1-{7-[(dimethylamino)methyl]-6,7-dihydro-3H-cyclobuta[e]indol-7-yl}cyclopentanol, x 1-{1-[(dimethylamino)methyl]-1,2-dihydrocyclobuta[a]naphthalen-1-yl}cyclopentanol, their isomers and addition salts thereof with a pharmaceutically acceptable acid or base. 12. Pharmaceutical compositions comprising as active ingredient at least one compound of formula (I) according to any one of claims 1 to 11, alone or in combination with one or more inert, non-toxic pharmaceutically acceptable excipients or carriers. 13. Pharmaceutical compositions according to claim 12 comprising at least one active ingredient according to any one of claims 1 to 11, for use as medicaments in the treatment of depression, panic attacks, obsessive-compulsive disorders, phobias, impulsive disorders, drug abuse, anxiety, obesity and bulimia.