Pyrrolopyridines as kinase inhibitors

摘要

Compounds of Formula (I) are useful for inhibition of CHK1 and/or CHK2. Methods of using compounds of Formula (I) and stereoisomers and pharmaceutically acceptable salts 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 of Formula I:or a stereoisomer or pharmaceutically acceptable salts thereof, wherein:
G is cyclohexyl or phenyl optionally substituted by 1-3 independent R4 groups, or when m is 0, G may additionally be absent or C1-C4 alkyl; R1 is —C(═O)ORa, —ORe, C3-C6 cycloalkyl, 5 or 6 membered heteroaryl, phenyl or —O-phenyl, wherein the heteroaryl, phenyl or —O-phenyl may be optionally substituted with one or two Rb groups; R2 is hydrogen, CH3, or —NHC(═O)Rf, R3 is hydrogen or C1-C3 alkyl; each R4 is independently halogen, CF3, OCF3 or CN; R5 and R6 are independently hydrogen or CH3; R7 and R8 are independently hydrogen or C1-C6 alkyl; Ra is C1-C4 alkyl; each Rb group is independently halogen, CN, OCH3 or C1-C4 alkyl optionally substituted with halogen, OH, oxo, 5 or 6 membered heteroaryl or NRgRh; Re is C1-C4 alkyl substituted with OH or 5 or 6 membered heterocycle; Rf is C1-C4 alkyl optionally substituted with OH, a 5 or 6 membered heterocycle optionally substituted with one or two groups selected from the group consisting of oxo, halogen, CN, CF3 and C1-C3 alkyl, or a 5 or 6 membered heteroaryl optionally substituted with one or two groups selected from the group consisting of halogen, CN, CF3 and C1-C3 alkyl; Rg and Rh are independently hydrogen or C1-C4 alkyl; m, n and p are independently 0 or 1; or R5 is hydrogen, R6 and R7 together with the atoms to which they are attached form an optionally substituted 5-6 membered heterocyclic ring having one ring nitrogen atom, and R8 is selected from the group consisting of hydrogen and C1-C4 alkyl optionally substituted with OH or O(C1-C3 alkyl) such that the compound of Formula I has the structure of Formula II: wherein Rc and Rd are independently hydrogen or C1-C4 alkyl; and r is 1 or 2.