BENZIMIDAZOLE DERIVATIVES AS BROMODOMAIN INHIBITORS

摘要

This application relates to chemical compounds which may act as inhibitors of, or which may otherwise modulate the activity of, a bromodomain-containing protein, including bromodomain-containing protein 4 (BRD4), and to compositions and formulations containing such compounds, and methods of using and making such compounds. Compounds include compounds of Formula (I);;wherein R1a, R1b, R2a, R2b, R3, R4a, R4b, and R5 are described herein.

主权项

1. A compound of Formula (Ib)wherein
R1a and R1b are each independently C1-6 alkyl optionally substituted with from 1 to 5 R20 groups; R2a and R2b are each independently H or halo; R3 is
—C(O)ORa, —NHC(O)ORa, —NHS(O)2Ra, or —S(O)2NRaRb; orselected from the group consisting of C1-10 alkyl, C1-10 alkoxy, amino, C5-10 aryl, C6-20 arylalkyl, C1-10 heteroalkyl, C5-10 heteroaryl, and C6-20 heteroarylalkyl, each of which is optionally substituted with from 1 to 5 R20 groups; R5 is
—C(O)ORa, —NHC(O)ORa, —NHS(O)2Ra, or —S(O)2NRaRb; orselected from the group consisting of H, C1-10 alkyl, C1-10 haloalkyl, C1-10 alkoxy, amino, C5-10 aryl, C6-20 arylalkyl, C1-10 heteroalkyl, C5-10 heteroaryl, and C6-20 heteroarylalkyl, each of which is optionally substituted with from 1 to 5 R20 groups; each Ra and Rb is independently selected from the group consisting of H, C1-10 alkyl, C5-10 aryl, C6-20 arylalkyl, C1-10 heteroalkyl, C5-10 heteroaryl, and C6-20 heteroarylalkyl, each of which is optionally substituted with from 1 to 5 R20 groups; and each R20 is independently selected from the group consisting of acyl, C1-10 alkyl, C1-10 alkoxy, amino, amido, amidino, C5-10 aryl, C6-20 arylalkyl, azido, carbamoyl, carboxyl, carboxyl ester, cyano, guanidino, halo, C1-10 haloalkyl, C1-10 heteroalkyl, C5-10 heteroaryl, C6-20 heteroarylalkyl, hydroxy, hydrazino, hydroxyl, imino, oxo, nitro, sulfinyl, sulfonic acid, sulfonyl, thiocyanate, thiol, and thione;
wherein the C1-10 alkyl, C5-10 aryl, C6-20 arylalkyl, C1-10 heteroalkyl, C5-10 heteroaryl, and C6-20 heteroarylalkyl groups are optionally substituted with from 1 to 3 substituents independently selected from C1-6 alkyl, C5-10 aryl, halo, C1-6 haloalkyl, cyano, hydroxyl, and C1-6 alkoxy;or a pharmaceutically acceptable salt thereof.