Hit generation and exploration: Imidazo[4,5-b]pyridine derivatives as inhibitors of Aurora kinases

A hit generation and exploration approach led to the discovery of 31 (2-(4-(6-chloro-2-(4-(dimethylamino)phenyl)-3H-imidazo[4,5-b]pyridin-7-yl)piperazin-1-yl)-N-(thiazol-2-yl)acetamide), a potent, novel inhibitor of Aurora-A, Aurora-B and Aurora-C kinases with IC50 values of 0.042, 0.198 and 0.227 μM, respectively. Compound 31 inhibits cell proliferation and has good microsomal stability.

Figure optionsDownload as PowerPoint slide