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Identification and synthesis of N'-(2-oxoindolin-3-ylidene)hydrazide derivatives against c-Met kinase. 2011
Zhongjie Liang, and
Dengyou Zhang, and
Jing Ai, and
Limin Chen, and
Hengshuai Wang, and
Xiangqian Kong, and
Mingyue Zheng, and
Hong Liu, and
Cheng Luo, and
Meiyu Geng, and
Hualiang Jiang, and
Kaixian Chen
Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
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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