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

  • Bioorg Med Chem Lett. 2011 Jun 15;21(12):3749-54. doi: 10.1016/j.bmcl.2011.04.064.
Zhongjie Liang  1 ,  Dengyou Zhang ,  Jing Ai ,  Limin Chen ,  Hengshuai Wang ,  Xiangqian Kong ,  Mingyue Zheng ,  Hong Liu ,  Cheng Luo ,  Meiyu Geng ,  Hualiang Jiang ,  Kaixian Chen
Affiliations
  • 1. Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
PMID: 21561768 DOI: 10.1016/j.bmcl.2011.04.064
Abstract

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 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.

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