Design, synthesis and molecular docking studies of some novel spiro[indoline-3, 4′-piperidine]-2-ones as potential c-Met inhibitors

Deregulation of receptor tyrosine kinase c-Met has been reported in human cancers and is considered as an attractive target for small molecule drug discovery. In this study, a series of spiro[indoline-3, 4′-piperidine]-2-ones were designed, synthesized and evaluated as novel c-Met inhibitors. The results showed that the majority of the compounds exhibited significant inhibitory effect on c-Met with IC50 values of 0.0147–17 μM in TR-FRET-based assay and IC50 values of 1.56–1400 μM in cell-based assay. Furthermore, our docking experiments verified the results and explained the molecular mechanism of eminent activities to c-Met.

Figure optionsDownload as PowerPoint slideHighlights
► We design and synthesize some novel spiro[indoline-3, 4′-piperidine]-2-ones.
► We investigate their inhibitory effect on c-Met with biological assay.
► Biological assay IC50 values are 0.0147–17 μM and cell IC50 values are 1.56–1400 μM.
► We explain molecular mechanism of eminent activities to c-Met by molecular docking.