Novel 5-(benzyloxy)pyridin-2(1H)-one derivatives as potent c-Met inhibitors

A series of novel 5-(benzyloxy)pyridin-2(1H)-ones were designed, synthesized and biologically evaluated for c-Met inhibition. The carbonyl oxygen of the pyridin-2(1H)-one was demonstrated to be an important factor for c-Met binding affinity. Various amides and benzoimidazoles at C-3 position of the pyridin-2(1H)-one core were investigated. A potent compound 12b with a c-Met IC50 of 12 nM was identified. This compound exhibited potent inhibition of EBC-1 cell associated with c-Met constitutive activation and showed high selectivity for c-Met than other tested 11 kinases.