COMPOUNDS AND COMPOSITIONS AS PROTEIN KINASE INHIBITORS

摘要

The invention provides novel pyrimidine and pyridine derivatives and pharmaceutical compositions thereof, and methods for using such compounds. For example, the pyrimidine and pyridine derivatives of the invention may be used to treat, ameliorate or prevent a condition which responds to inhibition of anaplastic lymphoma kinase (ALK) activity, focal adhesion kinase (FAK), zeta-chain-associated protein kinase 70 (ZAP-70), insulin-like growth factor (IGF-1R), or a combination thereof.

主权项

1. A method for treating a condition mediated by anaplastic lymphoma kinase, comprising administering to a subject in need of treatment, a therapeutically effective amount of a compound of Formula (1), or pharmaceutically acceptable salts thereof; wherein W is A1 and A4 are independently C; each A2 and A3 is C; R1 and R2 together form an optionally substituted 5-6 membered aryl, or heteroaryl or heterocyclic ring comprising 1-3 nitrogen atoms; R3 is (CR2)0-2SO2R12, (CR2)0-2SO2NRR12, (CR2)0-2C(O)O0-1R12, (CR2)0-2CONRR12, CO2NH2, or cyano; R4, R7 and R10 are independently H; R, R5 and R5′ are independently H or C1-6 alkyl; R6 is halo or O(C1-6 alkyl); R8 and R9 are independently C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, halo or X, or one of R8 and R9 is H; and provided one of R8 and R9 is X; X is (CR2)qY, cyano, C(O)O0-1R12, CONR(R12), CONR(CR2)pNR(R12), CONR(CR2)pOR12, CONR(CR2)pSR12, CONR(CR2)pS(O)1-2R12 or (CR2)1-6NR(CR2)pOR12; Y is an optionally substituted 3-12 membered carbocyclic ring, a 5-12 membered aryl, or a 5-12 membered heteroaryl or heterocyclic ring comprising N, O and/or S and attached to A2 or A3 or both via a carbon atom of said heteroaryl or heterocyclic ring when q in (CR2)qY is 0; R12 is an optionally substituted 3-7 membered saturated or partially unsaturated carbocyclic ring, or a 5-7 membered heterocyclic ring comprising N, O and/or S; aryl or heteroaryl; or R12 is H, C1-6 alkyl; and n is 0; and p and q are independently 0-4; and optionally in combination with a second therapeutic agent, wherein said condition is an autoimmune disease, a transplantation disease, an infectious disease or a cell proliferative disorder.