PHENYLPYRROLE DERIVATIVES AND THEIR USE AS DOPAMINE D3 ANTAGONISTS

摘要

Compounds of formula (I) wherein R1 represents C¿1-4?alkyl; R?4¿ represents a sulphonate group of formula R6OSO2 wherein R6 is an optionally substituted aryl or optionally substituted heteroaryl group, R?2, R3 and R5¿ each independently represent hydrogen, halogen, C¿1-4?alkyl, C1-4alkoxyl, C1-4alkoxyC1-4alkyl, C1-4alkylsulphonyl, trifluoromethylsulphonyl; optionally substituted arylsulphonyl, optionally substituted heteroarylsulphonyl, optionally substituted aralkylsulphonyl, optionally substituted heteroaralkylsulphonyl, nitro, cyano, amino, mono- or di-C1-4alkylamino, trifluoromethyl, trifluoromethoxy, hydroxyl, hydroxyC1-4alkyl, C1-4alkylthio, C1-4alkanoyl or C1-4alkoxycarbonyl; or R?1 and R2¿ together form a C¿2-4?alkyl chain, which chain may be optionally substituted by one or two C1-4alkyl groups, and R?3, R4 and R5¿ are as hereinbefore defined; or R?2 and R3¿ together form a phenyl ring, in which case R4 represents a group R6OSO2- as defined above and R5 represents hydrogen; and Y represents a group selected from (a) - (e) wherein in group (a): R?7 and R8¿ independently represent hydrogen, C¿1-6?alkyl, optionally substituted arylC1-6alkyl or optionally substituted heteroarylC1-6alkyl; R?9¿ represents C¿1-6?alkyl, C3-6alkenyl or C3-6cycloalkylC1-4alkyl; and R?10¿ represents C¿1-6?alkyl; C3-6alkenyl; C3-6cycloalkylC1-4alkyl, optionally substituted arylC1-4alkyl or optionally substituted heteroarylC1-4alkyl; or NR?9R10¿ forms a heterocyclic ring; in group (b): R11 represents C¿1-6?alkyl; C3-6alkenyl; C3-6cycloalkylC1-4alkyl, optionally substituted arylC1-4alkyl or optionally substituted heteroarylC1-4alkyl; and q is 1 to 4; in group (c): R?12 and R13¿ independently represent hydrogen, C¿1-6?alkyl, optionally substituted arylC1-6alkyl or optionally substituted heteroarylC1-6alkyl; R?14¿ represents an optionally substituted aryl or optionally substituted heteroaryl group; and Z represents -(CH¿2?)u wherein u is 2 to 8 or -(CH2)vCH=CH(CH2)w where v and w independently represent 1 to 3; in group (d) each of r and s independently represents an integer from 1 to 3; and in group (e) R?15¿ represents C¿1-6?alkyl, C3-6alkenyl or C3-6cycloalkylC1-4alkyl; and R?16, R17, R18 and R19¿ each independently represent hydrogen, halogen, C¿1-4?alkyl, C1-4alkoxy, C1-4alkoxyC1-4alkyl, nitro, cyano, trifluoromethyl, trifluoromethoxy, hydroxy, hydroxyC1-4alkyl, C1-4alkanoyl, C1-4alkoxycarbonyl, amino or mono- or di-C1-4alkylamino; X is CH2, S or O; t is zero, 1 or 2; and salts thereof have activity at dopamine receptors and are potentially useful in the treatment of psychoses such as schizophrenia.