SUBSTITUTED HYDROXAMIC ACIDS AND USES THEREOF

摘要

This invention provides compounds of formula (I):;wherein R1a, R1b, Ra, R2a, R2b, R1, and X 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, or C1-4 fluoroalkyl; one of R2a and R2b is R1, and the other is —C(O)—NH—OH; X is C(R1c)(R1d) or N—Rb; R1d is taken together with R1b to form a double bond; R1c is hydrogen, fluoro, bromo, —CH2—OR4aa, —CH2N(R4aa)2, or C1-4 alkyl; Rb is hydrogen, C1-6 alkyl, benzyl, or phenyl; or Rb is taken together with R1b to form a double bond; when X is C(R1c)(R1d), R1b is taken together with R1d to form a double bond; and when X is N—Rb, R1b is taken together with Rb to form a double bond, or is taken together with Ra to form a double bond, or is taken together with R1a to form C═O; R1a is hydrogen, fluoro, C1-4 alkyl, C1-4 fluoroalkyl, or G1; or when X is N—Rb, R1a can be taken together with R1b to form C═O; Ra is hydrogen, C1-4 alkyl, or G; or when X is N—Rb, R1b can be taken together with Ra to form a double bond; G is hydrogen, —R3, —L1—R3, or —L2—V1—R3; G1 is —NH2, —R3, —L1—R3, —V2—R3, —L1—V2—R3, or —V2—L1—R3; V1 is —O—, —N(R4a)—, —S—, —N(R4a)—C(O)—, —C(O)—N(R4a)—, —SO2—N(R4a)—, —N(R4a)—SO2—, —C(O)—, —SO2—, or —N(R4a)—C(O)—N(R4a)—; V2 is —O—, —N(R4a)—, —C(O)—N(R4a)—, —N(R4a)—C(O)—N(R4a)—, or —N(R4a)—C(O)—O—; L1 is an unsubstituted or substituted C1-4 alkylene chain; L2 is an unsubstituted or substituted C2-4 alkylene chain; each occurrence of R4aa is independently hydrogen or C1-4 alkyl; 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, unsubstituted or substituted C1-4aliphatic, 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.