Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Bioorg Med Chem Lett. 2011 Jun 15;21(12):3749-54. doi: 10.1016/j.bmcl.2011.04.064. Epub 2011 Apr 22.
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.
通过基于药效团的虚拟筛选和化学合成方法，鉴定出一系列 N'-(2-氧代吲哚啉-3-亚基)酰肼衍生物，它们对 c-Met 激酶具有中等抑制活性。研究了支架上各个位置的构效关系（SAR），并通过分子建模研究分析了其与 c-Met 激酶的结合模式。在这项研究中，鉴定出两种有效的化合物 D2 和 D25，它们对 c-Met 激酶的 IC50 值分别为 1.3 μM 和 2.2 μM。最后，根据从这项研究中提取的线索，讨论了进一步优化这个支架的未来发展方向。
