Indazoles as potential c-met inhibitors: Design, synthesis and molecular docking studies

• Synthesis of novel indazoles as potential c-Met inhibitors.
• Significant inhibitory effect on c-Met with biological assay IC50 and cell IC50 values.
• Docking experiments showed the molecular mechanism of eminent activities to c-Met.

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.

Novel indazoles were designed, synthesized and evaluated as c-Met inhibitors. Compounds exhibited significant inhibitory effect on c-Met with biological assay IC50 = 0.17–37 μM and cell IC50 = 5.45–1300 μM.Figure optionsDownload as PowerPoint slide