HUP9902949A2 - Aryl substituted cyclic amines as selective ligands of dopamine d3 receptor - Google Patents

Abstract

Aryl and heteroaryl fused cycloalkyl-amines of formulae (I), (II), and (III), and their salts, enantiomers, and racemates, are new. When n = 1, then X = JCONR4R5, JSO2R3, JSO2NR4R5, JNR4CONHR5, JNHSO2R3, JNHCOR3, or COR4; and Y = R4, GCONR4R5, GCN, GSO2NR4R5, OR6, GSO2R3, GNHSO2R3, halo or GNHCOR3; J = (CH2)m; G = (CH2)p; m, p = 0 or 1, but, when m = 0, then Y is not H or halo; when n = 0 and Y = OR9, then X = JCONR4R5, JSO2NR4R5, JNR4CONHR5, JSO2R3, JNHSO2R3, JNHCOR3 or COR4; or when n = 0 or 1, then XY in adjacent positions together = CONR10CO, CONR4(CH2)xNR10CO, CH2NR10CO, CH2CH2NR10CO, CH2CONR10, NR3CONR3, NR3COO, N=C(R7)NR3, or CH2N(R8)CH2; x = 0 or 1; R1, R2 = H, 1-8C alkyl, or aryl 1-8C alkyl; R3 = 1-8C alkyl, aryl, or aryl(1-6C alkyl); R4, R5 = H, 1-8C alkyl, aryl, or aryl(1-6C alkyl); R6 = H, 1-8C alkyl, aryl(1-6C alkyl), CF3SO2-aryl, 1-8C alkylsulphonyl, arylsulphonyl, or aryl(1-6C alkylsulphonyl); R7 = H, CONR4R4, SO2NR4R4, or SO2R4; R8 = 1-8C alkyl, aryl 1-6C alkyl, aryl, CONR4R4, COR4, SO2NR4R4, or SO2R4, provided in each case that R4 is not H; R9 = 2-8C alkyl (optionally substituted by 1-3 halo), aryl, or aryl(1-6C alkyl); and R10 = H, 1-8C alkyl, aryl, aryl(1-6C alkyl), arylsulphonyl, or arylsulphonyl(1-6C alkyl); one of A-D = N, the others = CH; k = 1 or 2; X', Y' = (i) substituted at A, B, C or D and X' = JCONR4R5, JCN, OSO2R3, JSO2NR4R5, JNR4CONHR5, JSO2R3, JNHSO2R3, JNHCOR3, or COR4; Y' = R4, GCONR4R5, GCN, GSO2NR4R5, OR61, OSO2R3, GSO2R3, GNHSO2R3, halo or GNHCOR3 (provided that when m = 0, then Y' is not H or halo); (ii) jointly in adjacent positions CONR4CO, CH2NR4CO, CH2CONR4 or CH2N(R4)CH2; R61 = H, MeSO2, CF3SO2, arylsulphonyl, 1-8C alkyl, aryl, or aryl 1-6C alkyl; one of E, F = N, the other = S; X" = JCONR4R5, JCN, JSO2NR4R5, JNR4CONHR5, JSO2R3, JNHSO2R3, JNHCOR3 or COR4.