Aminophenyl piperidines and piperazines have farnesyl protein transferase and geranyl geranyl protein transferase inhibiting activity for treatment of cancers and other disorders

摘要

Aminophenyl piperidine and piperazine derivatives (I), their salts, solvates, optical isomers and mixtures. Aminophenyl piperidine and piperazine derivatives (I), their salts, solvates, optical isomers and mixtures W' = H, COR6, CSR6, SO2R6, CO(CH2)nR6, or (CH2)nR7; X' = CH or N; Y' = (CH2)n, CO, CH2CO, CH=CH-CO, or CH2CH2CO, such that when it is not (CH2)n, W = H; Z = a heterocycle as defined below; R1 = H, 1-6C alkyl, halo, OCH3, or CF3; R2 and R3 = H or 1-6C alkyl; R4 = H, 1-6C alkyl (optionally substituted by aryl, cyanophenyl, nitrophenyl, aminophenyl, methoxyphenyl, hydroxyphenyl, heterocyclyl, halo, CN, NO2, OR2, SR2, NR2R3, COOR2), aryl or heterocyclyl; R5 = H, COR7, SO2R7, (CH2)nR7, CO(CH2)nR7, CO(CH2)nOR7, (CH2)nCSNR7R8, (CH2)mNHCOR7, (CH2)mNHCONR7R8, or (CH2)mNHCSR7R8; R6 = phenyl or naphthyl (optionally substituted by 1-6C alkyl, halo, phenyl, naphthyl, CN, NO2, CF3, OR7, SR7, NR7R8, COOR7, CONR7R8, or COR7), 1-6C alkyl, cycloalkyl, heterocycle, or NR7R8; R7 and R8 = H, 1-15C alkyl (optionally substituted by halo, COOCH3, COOH, OCH3, OH, CF3, CN, SCH3), cycloalkyl (optionally substituted by halo, OCH3, OH, CF3, CN, or SCH3), alkyl cycloalkyl ((optionally substituted by halo, OCH3, OH, CF3, CN, or SCH3), heterocycle, alkyl heterocycle, aryl or alkaryl, or R7 and R8 when they are adjacent may be taken together with the N to form a 4 - 6 membered ring; n = 0 - 10; and m = 2 - 10. Independent claims are also included for: (1) preparation of (I) by condensation of (V); and (2) preparation of (I) by condensation of (VIII). R'4 = a precursor of R4; and P1 = a protecting group.