O-Linked Triazolotriazines: Potent and Selective c-Met Inhibitors

Abstract

The HGF/c-Met signaling pathway mediates a variety of important biological activities, but dysregulation of the pathway is also closely associated with poor prognosis in a wide range of human cancers. c-Met is considered to be among the most promising therapeutic targets for anticancer drug discovery. Herein we report the discovery of a series of O-linked triazolotriazines that show sub-nanomolar inhibition of c-Met activity. Among these new compounds, 6 a exhibits high c-Met inhibitory potency in both enzymatic and cellular assays with great selectivity.

Highly selective c-Met inhibitor: c-Met is considered one of the most promising therapeutic targets for anticancer drug discovery. Herein we report a series of O-linked triazolotriazines that inhibit c-Met at sub-nanomolar concentrations. Compound 6 a exhibits high c-Met inhibitory potency in both enzymatic and cellular assays with great selectivity.