Design, synthesis and evaluation of highly selective pyridone-based class II MET inhibitors

A novel series of class II MET inhibitors has been designed that utilize 2-pyridone to conformationally restrain key pharmacophoric groups within the molecule via a scaffold-hopping strategy. Integrated molecular docking and SAR studies resulted in the discovery of a novel class of pyridone MET inhibitor with high potency (IC50 of 0.005 μM) and efficient selectivity (>5000 fold) to VEGFR-2, c-Kit and RET kinase.