OXAZOLE AND THIAZOLE COMPOUNDS AS BETA-CATENIN MODULATORS AND USES THEREOF

摘要

A series of oxazole and thiazole compounds are shown herein to be small molecule inhibitors of the Wnt pathway that specifically target the activity of the stabilized pool of β-cat oxazole and thiazole compounds are disclosed that have a formula represented by the following:;;The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, cancer, and others.

主权项

1. A method for preventing, treating or ameliorating in a mammal a disease or condition that is causally related to the aberrant activity of the Wnt signaling pathway in vivo, which comprises administering to the mammal an effective disease-treating or condition-treating amount of a compound according to formula I:wherein A is A1, A2 , or A3 ;A1 isA2 isA3 is
x is 1, when A is A1 or A2; or x is 0, when A is A3; L1 is S, SO or SO2; m1 is 1, 2 or 3; n is 1, 2, 3, 4 or 5; L2 is substituted or unsubstituted C1-C7 alkylene or heteroalkylene; each R1, R2a, R2b, R2c, and R2d is independently selected from hydrogen, halo, and substituted or unsubstituted C1-C6 alkyl; R2 is selected from aryl or heteroaryl, unsubstituted or substituted with one or more R4; R3 is hydroxy, alkoxy, substituted or unsubstituted amino or cycloheteroalkyl; or when A is A3, R3 is R5; each R4 and R5a is independently selected from H, alkyl, substituted alkyl, acyl, substituted acyl, substituted or unsubstituted acylamino, substituted or unsubstituted alkylamino, substituted or unsubstituted alkythio, substituted or unsubstituted alkoxy, alkoxycarbonyl, substituted alkoxycarbonyl, substituted or unsubstituted alkylarylamino, arylalkyloxy, substituted arylalkyloxy, amino, aryl, substituted aryl, arylalkyl, substituted or unsubstituted sulfonyl, substituted or unsubstituted sulfinyl, substituted or unsubstituted sulfanyl, substituted or unsubstituted aminosulfonyl, substituted or unsubstituted arylsulfonyl, azido, carboxy, substituted or unsubstituted carbamoyl, cyano, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloheteroalkyl, substituted or unsubstituted dialkylamino, halo, heteroaryloxy, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroalkyl, hydroxy, nitro, and thiol; and R5 is selected from aryl or heteroaryl, unsubstituted or substituted with one or more R5a; or a pharmaceutically acceptable salt, solvate or prodrug thereof; and stereoisomers, isotopic variants and tautomers thereof.