SUBSTITUTED TETRAHYDROISOQUINOLINE DERIVATIVES AS MODULATORS OF DOPAMINE D3 RECEPTORS

摘要

Compounds of formula (I), wherein R1 represents a substituent selected from a hydrogen or halogen atom; a hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, trifluoromethanesulfonyloxy, pentafluoroethyl, C¿1-4?alkyl, C1-4alkoxy, arylC1-4alkoxy, C1-4alkylthio, C1-4alkoxyC1-4alkyl, C3-6cycloalkylC1-4alkoxy, C1-4alkanoyl, C1-4alkoxycarbonyl, C1-4alkylsulphonyl, C1-4alkylsulphonyloxy, C1-4alkylsulphonylC1-4alkyl, arylsulphonyl, arylsulphonyloxy, arylsulphonylC1-4alkyl, C1-4alkylsulphonamido, C1-4alkylamido, C1-4alkylsulphonamidoC1-4alkyl, C1-4alkylamidoC1-4alkyl, arylsulphonamido, arylcarboxamido, arylsulphonamidoC1-4alkyl, arylcarboxamidoC1-4alkyl, aroyl, aroylC1-4alkyl, or arylC1-4alkanoyl group; a group R?3¿OCO(CH¿2?)p, R?3CON(R4¿)(CH2)¿p, R?3R4NCO(CH¿2?)p or R?3R4NSO¿2(CH2)p where each of R?3 and R4¿ independently represents a hydrogen atom or a C¿1-4?alkyl group or R?3R4¿ forms part of a C¿3-6? azacycloalkane or C3-6(2-oxo)azacycloalkane ring and p represents zero or an integer from 1 to 4; or a group Ar?1¿Z, wherein Ar1 represents an optionally substituted phenyl ring or an optionally substituted 5- or 6-membered aromatic heterocyclic ring and z represents a bond, O, S, or CH¿2; R?2 represents a hydrogen atom or a C¿1-4?alkyl group; q is 1 or 2; Ar represents an optionally substituted phenyl ring or an optionally substituted 5- or 6-membered aromatic heterocyclic ring; or an optionally substituted bicyclic ring system; and salts thereof. Compounds of formula (I) and their salts have affinity for dopamine receptors, in particular the D3 receptor, and thus potential in the treatment of conditions wherein modulation of the D3 receptor is beneficial, e.g. as antipsychotic agents.