Aurora Kinase Inhibitors Based on the Imidazo[1,2-a]pyrazine Core: Fluorine and Deuterium Incorporation Improve Oral Absorption and Exposure

摘要: Aurora kinases are cell cycle regulated serine/threonine that have been linked to cancer. Compound 1 was identified as a potent inhibitor but lacked oral bioavailability. Optimization of led the discovery series fluoroamine and deuterated analogues, exemplified by compound 25, with an improved pharmacokinetic profile. We found blocking oxidative metabolism at benzylic position decreasing basicity amine important obtaining compounds good biological profiles