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.

Compound 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 as PowerPoint slide