SERINE/THREONINE KINASE INHIBITORS

摘要

Compounds of Formula I or a stereoisomer, tautomer, prodrug or pharmaceutically acceptable salt thereof are provided, which are useful for the treatment of hyperproliferative, pain and inflammatory diseases. Methods of using compounds of Formula I or a stereoisomer, tautomer, prodrug or pharmaceutically acceptable salt thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.;

主权项

1. A compound selected from Formula I:or a stereoisomer, tautomer, prodrug or pharmaceutically acceptable salt thereof, wherein:
X1 is selected from CH and N; X2 is selected from CR5 and N; Y1 is selected from CR6 and N; Y2 is selected from CR7 and N; R1 is selected from (a) C1-C6 alkyl optionally substituted with one or more groups independently selected from halogen, ORa, NRbRc, oxo, CN, C3-C6 cycloalkyl and a 3 to 7 membered heterocycle, (b) C3-C7 cycloalkyl optionally substituted with one or more groups independently selected from halogen, ORa, CN and C1-C3 alkyl optionally substituted with one or more groups independently selected from halogen and ORd, (c) phenyl optionally substituted with one or more groups independently selected from halogen, ORa, CN, C3-C6 cycloalkyl and C1-C3 alkyl optionally substituted with one or more groups independently selected from halogen and ORd, (d) a 3 to 7 membered saturated or partially unsaturated heterocycle optionally substituted with one or more groups independently selected from halogen, ORa, oxo, CN, C3-C6 cycloalkyl and C1-C3 alkyl optionally substituted with one or more groups independently selected from halogen and ORd, (e) a 5 to 6 membered heteroaryl optionally substituted with one or more groups independently selected from halogen, ORe, oxide, CN, C3-C6 cycloalkyl and C1-C3 alkyl optionally substituted with one or more groups independently selected from halogen, oxo and ORd, and (f) a 7 to 10 membered bicyclic heterocycle optionally substituted with one or more groups independently selected from halogen, ORa, oxo, CN, C3-C6 cycloalkyl and C1-C3 alkyl optionally substituted with one or more groups independently selected from halogen and ORd; R2 is selected from (a) hydrogen, (b) C1-C6 alkyl optionally substituted with one or more groups selected from ORf, oxo, NH2, NH(C1-C3 alkyl) and N(C1-C3 alkyl)2, (c) C1-C6 alkenyl optionally substituted with one or more groups selected from ORf, oxo, NH2, NH(C1-C3 alkyl) and N(C1-C3 alkyl)2, (d) C1-C6 alkynyl optionally substituted with one or more groups selected from ORf, oxo, NH2, NH(C1-C3 alkyl) and N(C1-C3 alkyl)2, (e) C3-C6 cycloalkyl optionally substituted with one or more groups selected from ORf and Rg, (f) phenyl optionally substituted with one or more groups selected from ORf and Rg, (g) a 3 to 7 membered heterocycle optionally substituted with one or more groups selected from ORf and Rg, and (h) a 5 to 6 membered heteroaryl optionally substituted with one or more groups selected from ORf and Rg; R3 is selected from (a) (CRhRi)x-phenyl, wherein the phenyl may be optionally substituted with one or more Rj groups, (b) (CRhRi)x-(5 to 6 membered heteroaryl), wherein the heteroaryl may be optionally substituted with one or more Rj groups, (c) (CRhRi)x-(9 to 10 membered bicyclic heterocycle), wherein the heterocycle may be optionally substituted with one or more Rj groups, and (d) (CRhRi)x-(9 to 10 membered bicyclic heteroaryl), wherein the heteroaryl may be optionally substituted with one or more Rj groups; each R4, R5, R6 and R7 is independently selected from hydrogen, halogen and C1-C3 alkyl; each Ra, Rb, Rc, Rd and Re are independently selected from hydrogen and C1-C6 alkyl; Rf is selected from hydrogen and C1-C6 alkyl optionally substituted with one or more groups selected from oxo, NH2, NH(C1-C3 alkyl) and N(C1-C3 alkyl)2; each Rg is C1-C6 alkyl; Rh and Ri are independently selected from hydrogen, ORk and C1-C6 alkyl optionally substituted with ORm; each Rj is independently selected from halogen, CN, cyclopropyl, C1-C6 alkyl optionally substituted with halogen, and C1-C6 alkoxy optionally substituted with halogen; Rk and Rm are independently hydrogen or C1-C3 alkyl; and x is 0 or 1.