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

Authors：Liang Zhongjie; Zhang Dengyou; Ai Jing; Chen Limin; Wang Hengshuai; Kong Xiangqian; Zheng Mingyue; Liu Hong^*; Luo Cheng; Geng Meiyu; Jiang Hualiang; Chen Kaixian

Source：Bioorganic and Medicinal Chemistry Letters, 2011, 21(12): 3749-3754.

DOI：10.1016/j.bmcl.2011.04.064

• c-Met kinase
• N '-(2-Oxoindolin-3-ylidene)hydrazide
• Pharmacophore-based virtual screening

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.

• Institution
  中国科学院上海药物研究所; 苏州大学