Identification and synthesis of N′-(2-oxoindolin-3-ylidene)hydrazide derivatives against c-Met kinase

A series of N′-(2-oxoindolin-3-ylidene)hydrazide derivatives were identified as moderately potent inhibitors against c-Met kinase by pharmacophore-based virtual screening and chemical synthesis methods. The structure–activity relationship (SAR) at various positions of the scaffold was investigated and its binding mode with c-Met kinase was analyzed by molecular modeling studies. In this study, two potent compounds D2 and D25, with IC50 value at 1.3 μM and 2.2 μM against c-Met kinase respectively, were identified. Finally, based on the clues extracted from this study, future development for the optimization of this scaffold was discussed.

Graphical abstractCompound D2 was discovered by pharmacophore-based virtual screening against SPECS database. Based on the SAR and binding modes analysis, modifications on the N′-(2-oxoindolin-3-ylidene)hydrazide scaffold were proposed.Figure optionsDownload full-size imageDownload as PowerPoint slide