Spirocyclic derivatives as histone deacetylase inhibitors

摘要

This invention is related to new histone deacetylase inhibitors according to the general formula (I), wherein: m and n are independently zero or an integer from 1 to 4; p is zero or an integer from 1 to 3, with the proviso that when p is zero, n and m cannot be both 1; R is hydrogen; C1-C6 alkyl, optionally substituted by C3-C8 cycloalkyl, C6-C10 aryl or hetero(C2-C9)aryl; (CO)R2; (SO2)R3; C3-C8 cycloalkyl; C6-C10 aryl; or hetero(C2-C9)aryl; R1 is halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy; Y is CH2 or NR4; Z is C═R5; and R2, R3, R4, and R5 are as further defined in the specification; and pharmaceutical acceptable salts thereof.;

主权项

1. Compounds of formula (I) wherein: m, n are independently zero or an integer from 1 to 4; p is, zero or an integer from 1 to 3; R is hydrogen; C1-C6 alkyl, optionally substituted by C3-C8 cycloalkyl, C6-C10 aryl, or hetero(C2-C9)aryl; (CO)R2; (SO2)R3; C3-C8 cycloalkyl; C6-C10 aryl or hetero(C2-C9)aryl; R1 is halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C1-C6 haloalkoxy; Y is CH2 or NR4; Z is C═R5; R2 is C1-C6 alkyl, optionally substituted by C6-C10 aryl or by hetero(C2-C9)aryl; C6-C10 aryl; hetero(C2-C9)aryl; O—C1-C6 alkyl, optionally substituted by C6-C10 aryl; O—(C6-C10-aryl) or NR6R7; R3 is C1-C6 alkyl, optionally substituted by C6-C10 aryl or by hetero(C2-C9)aryl; C6-C10 aryl or hetero(C2-C9)aryl; R4 is hydrogen; C1-C6 alkyl, optionally substituted by C6-C10 aryl or by hetero(C2-C9)aryl; R5 is oxygen or NOR8; R6 is hydrogen; C1-C6 alkyl, optionally substituted by C6-C10 aryl or by hetero(C2-C9)aryl; C6-C10 aryl or hetero(C2-C9)aryl; R7 is hydrogen; C1-C6 alkyl, optionally substituted by C6-C10 aryl or by hetero(C2-C9)aryl; or R6 and R7 together with the nitrogen to which they are bound form a C4-C9-heterocyclic ring, optionally containing one or more further heteroatoms in the ring selected from NR9, O or S; R8 is hydrogen; C1-C6 alkyl, optionally substituted by C6-C10 aryl; R9 is hydrogen; C1-C6 alkyl, optionally substituted by C6-C10 aryl or by hetero(C2-C9)aryl; C6-C10 aryl; hetero(C2-C9)aryl; (CO)R10; or (SO2)R11; R10 is C1-C6 alkyl, optionally substituted by C6-C10 aryl or by hetero(C2-C9)aryl; O—C1-C6 alkyl, optionally substituted by C6-C10 aryl; O—(C6-C10-aryl) or NR12R13; R11 is C1-C6 alkyl, optionally substituted by C6-C10 aryl or by hetero(C2-C9)aryl; C6-C10 aryl or hetero(C2-C9)aryl; R12 is hydrogen; C1-C6 alkyl, optionally substituted by C6-C10 aryl or by hetero(C2-C9)aryl; C6-C10 aryl or hetero(C2-C9)aryl; R13 is hydrogen; C1-C6 alkyl, optionally substituted by C6-C10 aryl or hetero(C2-C9)aryl; and the pharmaceutically acceptable salts thereof; provided that when p is zero, then n and m cannot be both 1.