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.

受体酪氨酸激酶c-Met的失调在人类癌症中已有报道，被认为是发现小分子药物的诱人靶标。在这项研究中，设计，合成和评估了一系列螺[吲哚啉-3，4'-哌啶] -2-one，作为新型c-Met抑制剂。结果表明，大多数化合物显示对c-Met的带IC显著抑制效果₅₀在基于TR-FRET的测定0.0147-17μM的值和IC _50个1.56-1400μM的值在基于细胞的测定。此外，我们的对接实验验证了结果并解释了c-Met突出活性的分子机制。