Patent EA-003302-B1 (EA)
Title: Derivatives of benzo[3,4]cyclobuta[1,2-c]pyrrole, their use as an inhibitor of serotonin
Inventor: PEGLION JEAN-LOUIS
IPC: C07D209/70
Filed: 2000-03-24
Abstract: 1. A compound, with a cis ring junction, wherein: R1, R2 and R3, which may be the same or different, each independently of the others represents a substituent selected from hydrogen, halogen, linear or branched (C1-C6)alkoxy, linear or branched (C1-C6) trihaloalkyl, or two of R1, R2 and R3 in adjacent positions represent (C1-C6) alkylenedioxy; R4 represents a group selected from hydrogen, linear or branched (C1-C6)alkyl, aryl(C1-C6)alkyl in which alkyl is linear or branched, heterocycloalkyl, heterocycloalkyl-(C.sub.1 -C.sub.6)alkyl in which alkyl is linear or branched, R5 represents a group selected from aryl, optionally substituted aryl, heteroaryl, and optionally substituted heteroaryl, n represents an integer of 1 to 3 inclusive, its isomers and addition salts thereof with a pharmaceutically acceptable acid or base, cycloalkyl being understood to mean a monocyclic saturated(C3-C8)ring system, furthermore, aryl being understood to mean phenyl, indanyl, and optionally substituted aryl being understood to mean aryl, as defined hereinbefore, optionally substituted by one or more substituents, which may be the same or different, selected from halogen, hydroxy, linear or branched (C1-C6)alkyl, linear or branched (C1-C6)alkoxy, cycloalkyl, adamantyl, linear or branched (C1-C6)trihaloalkyl, oxo, and (C1-C2)alkylenedioxy, heteroaryl being likewise understood to mean aryl as defined hereinbefore containing one, two, or three heteroatoms, which may be the same or different, selected from oxygen, nitrogen, and sulphur, and optionally substituted heteroaryl being understood to mean heteroaryl as defined hereinbefore optionally substituted by one or more substituents; which may be the same or different, as defined for substitutes of aryl. 2. A compound of claim 1, wherein R5 represents heteroaryl, their isomers and addition salts with pharmaceutically acceptable acid or base. 3. A compound of claim 1, wherein R5 represents methylenedioxyphenyl or ethylenedioxyphenyl, their isomers and addition salts with pharmaceutically acceptable acid or base. 4. A compound of claim 1, wherein n is 1, their isomers and addition salts with pharmaceutically acceptable acid or base. 5. A compound of claim 1, wherein n is 2, their isomers and addition salts with pharmaceutically acceptable acid or base. 6. A compound of claim 1, wherein R4 represents hydrogen, linear or branched (C1 -C6)alkyl, or aryl-(C1 -C6)alkyl in which alkyl is linear or branched, their isomers and addition salts with pharmaceutically acceptable acid or base. 7. A compound of claim 1, which is selected from cis-3a-[(3,4-methylenedioxyphenoxy)methyl]-2,3,3a,7b-tetrahydro-1H-benzo[3 ,4]cyclobuta[1,2-c]pyrrole, and its hydrochloride salt. 8. A compound of claim 1, which is cis-2-benzyl-5-methoxy-3a-[(3,4-methylenedioxyphenoxy)-methyl]-2,3,3a,7b-t etrahydro-1H-benzo[3,4]cyclobuta[1,2-c]pyrrole. 9. A compound of claim 1, which is selected from cis-5-methoxy-3a-[(3,4-methylenedioxyphenoxy) methyl]-2,3,3a,7b-tetrahydro -1H-benzo[3,4]cyclobuta[1,2-c]pyrrole, and its hydrochloride salt. 10. A compound of claim 1, which is cis-5-methoxy-2-methyl-3a-[(3,4-methylenedioxyphenoxy)-methyl]-2,3,3a,7b-t etrahydro-1 H-benzo[3,4]cyclobuta[1,2-c]pyrrole. 11. A compound of claim 1, which is selected from cis-6-trifluoromethyl-3a-[(3,4-methylenedioxyphenoxy)-methyl]-2,3,3a,7b-te trahydro-1H-benzo[3,4]cyclobuta[1,2-c]-pyrrole, and its hydrochloride salt. 12. A compound of claim 1 which is selected from cis-6-fluoro-3a-[(3,4-methylenedioxyphenoxy)-methyl]-2,3,3a,7b-tetrahydro-1H-benzo[3,4]cyclobuta[1,2-c]pyrrole, and its hydrochloride salt. 13. A pharmaceutical composition useful for treatment of depression comprising as active principle an effective amount of a compound as claimed in claim 1, in combination with one or more pharmaceutically acceptable excipients or carriers. 14. A pharmaceutical composition comprising at least one active ingredient according to any of claims 1-12 to use as an inhibitor of serotonin recapture while treating for depression, panic attacks, obsessive-compulsive disorders, phobias, impulsive disorders, drug abuse or anxiety.