SUBSTITUTED HYDROXAMIC ACIDS AND USES THEREOF

摘要

This invention provides compounds of formula (I):;wherein ring A, X1, X2, X3, R2, R4b, R10, and G 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: ring A is an aromatic 6-membered ring connected through one of positions (a) or (b);
X1 is CR1 or N;(i) when ring A is connected through position (a), X2 is C; and X3 is CR1 or N; or(ii) when ring A is connected through position (b), X3 is C; and X2 is CR1 or N; each occurrence of R1 is independently hydrogen, halogen, C1-4 alkyl, C1-3 fluoroalkyl, —O—C1-3 alkyl, —O—C1-3 fluoroalkyl, cyano, hydroxy, —NHC(O)C1-3 alkyl, —C(O)NHC1-3 alkyl, —NHC(O)NHC1-3 alkyl, or —NHS(O)2C1-3 alkyl. each occurrence of R10 is independently hydrogen, halogen, hydroxy, —O—C1-3 alkyl, or —O—C1-3 fluoroalkyl; R2 is C1-6 aliphatic, C1-6 fluoroaliphatic, or unsubstituted or substituted 6-10-membered aryl; R4b is hydrogen, or C1-4 aliphatic; G is —R3, -V1—R3, -V1-L1-R3, -L2-V1—R3, -L2-V2—R3, or -L1-R3; L1 is an unsubstituted or substituted C1-3 alkylene chain; L2 is an unsubstituted or substituted C2-3 alkylene chain; V1 is —C(O)—, —C(O)—CRA═CRA—, —C(O)—N(R4a)—, —C(O)—O—, or —S(O)2—; V2 is —N(R4a)—, —N(R4a)—C(O)—, —SO2—N(R4a)—, —N(R4a)—SO2—, —O—, —S—, —S(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 1-5 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; each occurrence of RA is independently hydrogen, fluoro, or unsubstituted or substituted C1-4 aliphatic; and each occurrence of R4a is independently hydrogen, or unsubstituted or substituted C1-4 aliphatic.