|
|||||
|
|
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 |
| Institution: | a Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China b Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China c Center for Systems Biology, Soochow University, Suzhou 215006, China d School of Pharmacy, East China University of Science and Technology, Shanghai, China |
| 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 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. |
| Keywords: | c-Met kinase N&prime -(2-Oxoindolin-3-ylidene)hydrazide Pharmacophore-based virtual screening |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ | |