Substituted indolyl alkyl amino derivatives as novel inhibitors of histone deacetylase

摘要

This invention comprises the novel compounds of formula (I);
wherein R1, R2, R3, X and Y have defined meanings, having histone deacetylase inhibiting enzymatic activity; their preparation, compositions containing them and their use as a medicine.

主权项

1. A method of inhibiting breast carcinoma in a subject comprising administering to the subject a therapeutically effective amount of a compound of formula (I), the N-oxide forms, the pharmaceutically acceptable addition salts and the stereo-chemically isomeric forms thereof, wherein each n is an integer with value 0, 1 or 2 and when n is 0 then a direct bond is intended; each m is an integer with value 1 or 2; each X is independently N or CH; each Y is independently O, S, or NR4; wherein each R4 is hydrogen, C1-6alkyl, C1-6alkyloxyC1-6alkyl, C3-6cycloalkyl, C3-6cycloalkylmethyl, phenylC1-6alkyl, —C(═O)—CHR5R6 or —S(═O)2—N(CH3)2; wherein each R5 and R6 is independently hydrogen, amino, C1-6alkyl or aminoC1-6alkyl; and when Y is NR4 and R2 is on the 7-position of the indolyl then R2 and R4 together can form the bivalent radical
—(CH2)2—  (a-1), or—(CH2)3—  (a-2); R1 is hydrogen, C1-6alkyl, hydroxyC1-6alkyl, C1-6alkylsulfonyl, C1-6alkylcarbonyl or mono- or di(C1-6alkyl)aminosulfonyl; R2 is hydrogen, hydroxy, amino, halo, C1-6alkyl, cyano, C2-6alkenyl, polyhaloC1-6alkyl, nitro, phenyl, C1-6alkylcarbonyl, hydroxycarbonyl, C1-6alkylcarbonylamino, C1-6alkyloxy, or mono- or di(C1-6alkyl)amino; R3 is hydrogen, C1-6alkyl, or C1-6alkyloxy; and when R2 and R3 are on adjacent carbon atoms, they can form the bivalent radical —O—CH2—O—.