Fused pyrimidine compounds and use thereof

摘要

The present invention provides fused pyrimidine compounds of the general Formula (I):;
or a salt thereof, wherein the variables are as defined in the specification. Fused pyrimidine compounds of the general Formula (I) are provided as kinase inhibitors, such as multi-kinase inhibitors. In one aspect, fused pyrimidine compounds of the general Formula (I) are provided as IGF-IR inhibitors. The compounds may be used in a method of treating cancer. Pharmaceutical compositions containing a fused pyrimidine compounds of the general Formula (I) and a pharmaceutically acceptable carrier are also provided, as are kits containing a fused pyrimidine compound of the general Formula (I) or salt thereof and instructions for use, e.g., in a method of treating cancer.

主权项

1. A compound of the formula (I):or a salt or N-oxide thereof, wherein:
D is hydrogen; unsubstituted C1-C6 alkyl; C1-C6 alkyl substituted by 1 to 5 substituents independently selected from the group consisting of hydroxy, heteroaryl, and heteroaryl substituted by C1-C6 alkyl; unsubstituted aryl; unsubstituted heteroaryl; heteroaryl substituted by 1 to 5 substituents independently selected from the group consisting of alkoxy, amino, halo, hydroxy and thioalkyl; unsubstituted C3-C8 cycloalkyl; unsubstituted heterocyclyl; or heterocyclyl substituted by 1 to 5 substituents independently selected from unsubstituted acyl, acyl substituted by amino, C1-C6 alkyl and oxo; wherein the heteroaryl of D is selected from the group consisting of pyridyl, pyrimidyl, pyrazinyl, thiazolyl, oxazolyl, pyrazolyl, furanyl and thiadiazolyl, and the heterocyclyl of D is selected from the group consisting of pyrrolidinyl and piperidinyl; E is unsubstituted 5-membered heteroaryl or 5-membered heteroaryl substituted by 1 to 4 substituents independently selected from the group consisting of unsubstituted acylamino, hydroxy, unsubstituted C1-C6 alkyl, C1-C6 alkyl substituted by hydroxy, unsubstituted C3-C8 cycloalkyl, and C3-C8 cycloalkyl substituted by hydroxy or C1-C6 alkyl; each j, k, m, and n is independently 0 or 1; each RA1, RA2, RA3, RA4, RA5, RA6, RA7, RA8, RA9 and RA10, where present, is independently hydrogen, unsubstituted C1-C6 alkyl, halo, hydroxy, or taken together with a geminal RA(1-10) group and the carbon to which they are attached to form a carbonyl moiety or a thiocarbonyl moiety; RD is hydrogen; X is O or S; RZ is hydrogen, or unsubstituted C1-C6 alkyl; each RZ1 and RZ2 is independently hydrogen, or unsubstituted C1-C6 alkyl; each RZ3, RZ4, RZ5, RZ6, RZ7 and RZ8, where present, is independently hydrogen, unsubstituted C1-C6 alkyl, halo, hydroxy, —OR1, —O—C1-C6 alkylene-P(O)(OH)2, —OC(O)R8, unsubstituted tetrazolyl, tetrazolyl substituted by C1-C6 alkyl, or is taken together with a geminal RZ(3-8) group and the carbon to which they are attached to form a carbonyl moiety; each R1 is independently unsubstituted C1-C6 alkyl; each R8 is independently unsubstituted C1-C6 alkyl.