SUBSTITUTED HYDOXAMIC ACIDS AND USES THEREOF

摘要

This invention provides compounds of formula (I):;wherein R1, R1b, R2a, R2b, R2c, and R2d have values as described in the specification, useful as inhibitors of HDAC6. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of proliferative, inflammatory, infectious, neurological or cardiovascular diseases or disorders.

主权项

1. A compound of formula (I): or a pharmaceutically acceptable salt thereof; wherein: each occurrence of R1 is independently hydrogen, chloro, fluoro, —O—C1-4 alkyl, cyano, hydroxy, C1-4 alkyl, C1-4 fluoroalkyl, —N(C1-4 alkyl)2, —NH(C1-4 alkyl), —NH2, or O—C1-4 fluoroalkyl; R2a is G or R1a; R2b is G or R1a; R2c is G or R1a; R2d is G or R1a; provided that one and only one of R2a, R2b, R2c, and R2d is G; each occurrence of R1a is independently hydrogen, fluoro, C1-4 alkyl, or C1-4 fluoroalkyl; each occurrence of R1b is independently hydrogen, fluoro, or C1-4 alkyl; or one occurrence of R1a and one occurrence of R1b on the same carbon atom can be taken together to form ═O or a 3-6 membered cycloaliphatic; G is hydrogen, —R3, -V1-R3, -V1-L1-R3, -L1-V1-R3, or -L1-R3; L1 is an unsubstituted or substituted C1-3 alkylene chain; V1 is —C(O)—, —C(S)—, —C(O)—N(R4a)—, —C(O)—O—, —N(R4a)—, —N(R4a)—C(O)—, —N(R4a)—SO2—, —O—, —N(R4a)—C(O)—N(R4a)—, —N(R4a)—C(O)—O—, —O—C(O)—N(R4a)—, or —N(R4a)—SO2—N(R4a)—; R3 is unsubstituted or substituted C1-6 aliphatic, unsubstituted or substituted 3-10-membered cycloaliphatic, unsubstituted or substituted 4-10-membered heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, unsubstituted or substituted 6-10-membered aryl, or unsubstituted or substituted 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and each occurrence of R4a is independently hydrogen, or unsubstituted or substituted C1-4 aliphatic; or when V1 is —N(R4a)—C(O)—, —N(R4a)—SO2—, or —N(R4a)—C(O)—N(R4a)—, one occurrence of R4a can be taken together with an R1a attached to a ring carbon atom that is not adjacent to the ring carbon atom to which G is attached to form a substituted or unsubstituted 5-7 membered bridged heterocyclyl; provided that the compound is other than 8-(2-amino-8-bromo-1,6-dihydro-6-oxo-9H-purin-9-yl)-5,6,7,8-tetrahydro-N-hydroxy-2-naphthalenecarboxamide.