Indazoles as potential c-Met inhibitors: design, synthesis and molecular docking studies.

ABSTRACT

Deregulation of the receptor tyrosine kinase c-Met has been implicated in several human cancers and is considered as an attractive target for small molecule drug discovery. In this study, a series of indazoles were designed, synthesized and evaluated as novel c-Met inhibitors. The results showed that the majority of the compounds exhibited significant inhibition on c-Met and compound 4d showed highest activity against c-Met with IC50 value of 0.17 µM in TR-FRET-based assay and IC50 value of 5.45 µM in cell-based assay as compared to other tested compounds. Molecular docking experiments verified the results and explained the molecular mechanism of pretty activities to c-Met.