CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS

摘要

Chemical entities that are effective as kinase inhibitors, pharmaceutical compositions and methods of treatment are disclosed. The chemical entities disclosed specifically inhibit signal transduction and cellular proliferation by modulating the activity of protein kinases to regulate and modulate abnormal or inappropriate cell proliferation, differentiation, or metabolism. The compounds include a pyrido[3,2-d]pyrimidine scaffold substituted with aromatic and heteroaromatic moieties.

主权项

1. A compound of Formula I:or a pharmaceutically acceptable salt thereof, wherein:
X3 is C—R12 or N; X4 is C—R13 or N; X5 is C—R14 or N; n is 0, 1, 2, 3, 4, or 5; m is 0, 1, 2, 3, 4, or 5;is aryl or heteroaryl;is aryl, heteroaryl, or heterocycloalkyl;
R6, R12, R13, R14, and each Z are independently hydrogen, cyano, halo, hydroxy, azido, nitro, carboxy, oxo, sulfinyl, sulfanyl, sulfonyl, optionally substituted alkoxy, optionally substituted cycloalkyloxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted heterocycloalkyloxy, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, optionally substituted amino, optionally substituted acyl, optionally substituted alkoxycarbonyl, optionally substituted aminocarbonyl, optionally substituted aminosulfonyl, or optionally substituted carbamimidoyl; and each Q is independently hydrogen, cyano, halo, hydroxy, azido, nitro, carboxy, oxo, sulfinyl, sulfanyl, sulfonyl, optionally substituted alkoxy, optionally substituted cycloalkyloxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted heterocycloalkyloxy, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, optionally substituted amino, optionally substituted acyl, optionally substituted alkoxycarbonyl, optionally substituted aminocarbonyl, optionally substituted aminosulfonyl, optionally substituted carbamimidoyl, or E; wherein E is an electrophilic group capable of forming a covalent bond with a nucleophile.