BENZIMIDAZOLONE 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, and X are described herein.;

主权项

1. A compound of Formula (I) wherein
R1a and R1b are each independently C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, C3-C6 cycloalkyl, or CH2—C3-C6 cycloalkyl;R2a and R2b are each independently H or halogen;R3 is
C5-C10 aryl, C5-C10 heteroaryl, or C5-C10 heteroarylalkyl, each of which is optionally substituted with from 1 to 5 R20 groups; or—S(O)2NHR4,
wherein R4 is C1-C6 alkyl or C3-C7 cycloalkyl, each of which is optionally substituted with from 1 to 5 R20 groups; ora moiety of the formula wherein
R6 is H, OH, or halogen; and R7 and R8 are each independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 heteroalkyl, C5-C12 aryl, C5-C12 heteroaryl, or C5-C12 heteroarylalkyl, each of which is optionally substituted with from 1 to 5 R20 groups; or
R6 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, phenyl, naphthyl, or C3-C12 heteroaryl; and R7 and R8 together form a C1-C6 alkylidene group having a double bond with the carbon to which each of R6, R7, and R8 are bound wherein each of the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, —C3-C6 cycloalkyl, phenyl, naphthyl, or C3-C12 heteroaryl groups is optionally substituted with from 1 to 5 R20 groups;X is N-Q, or O;Q is H, C1-C3 alkyl, C1-C3 haloalkyl, benzyl or substituted benzyl;each R20 is independently C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 heteroalkyl, C3-C6 heterocyclic, C5-C12 aryl, C5-C12 heteroaryl, halogen, oxo, —ORa, —C(O)Ra, —C(O)ORa, —C(O)NRaRb, —OC(O)NRaRb, —NRaRb, —NRaC(O)Rb, —NRaC(O)ORb, —S(O)0-2Ra, —S(O)2NRaRb, —NRaS(O)2Rb, —Ni, —CN, or —NO2, wherein each C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 heteroalkyl, C3-C6 heterocyclic, C5-C12 aryl, C5-C12 heteroaryl is optionally substituted with from one to five halogen, oxo, —ORa, —C(O)Ra, —C(O)ORa, —C(O)NRaRb, —OC(O)NRaRb, —NRaRb, —NRaC(O)Rb, —NRaC(O)ORb, —S(O)0-2Ra, —S(O)2NRaRb, —NRaS(O)2Rb, —N3, —CN, or —NO2;each Ra and Rb is independently H; or C1-C6 alkyl C3-C6 cycloalkyl, C1-C6 heteroalkyl, C3-C6 heterocyclic, C5-C12 aryl, C5-C12 heteroaryl, each of which is optionally substituted with from one to five R21; or Ra and Rb together with the atoms to which they are attached form a heterocycle, and;each R21 is independently C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 heteroalkyl, C3-C6 heterocyclic, C5-C12 aryl, C5-C12 heteroaryl, or halogen; or a pharmaceutically acceptable salt thereof.