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

摘要

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 IC(50) value at 1.3 mu M and 2.2 mu M 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.

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