Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
Bioorg Chem. 2017 Feb;70:126-132. doi: 10.1016/j.bioorg.2016.12.002. Epub 2016 Dec 19.
Receptor tyrosine kinase c-Met acts as an alternative angiogenic pathway in the process and contents of cancers. A series of imidazopyridine derivatives were designed and synthesized according to the established docking studies as possible c-Met inhibitors. Most of these imidazopyridine derivatives displayed nanomolar potency against c-Met in both biochemical enzymatic screens and cellular pharmacology studies. Especially, compound 7g exhibited the most inhibitory activity against c-Met with IC of 53.4nM and 253nM in enzymatic and cellular level, respectively. Following that, the compound 7g was docked into the protein of c-Met and the structure-activity relationship was analyzed in detail. These findings indicated that the novel imidazopyridine derivative compound 7g was a potential c-Met inhibitor deserving further investigation for cancer treatment.
受体酪氨酸激酶 c-Met 在癌症的发生和发展过程中充当了一种替代的血管生成途径。根据已建立的对接研究，我们设计并合成了一系列咪唑并吡啶衍生物，将其作为潜在的 c-Met 抑制剂。这些咪唑并吡啶衍生物中的大多数在生化酶筛选和细胞药理学研究中对 c-Met 均表现出纳摩尔级的抑制活性。特别是，化合物 7g 在酶和细胞水平上对 c-Met 的抑制活性最强，IC 分别为 53.4nM 和 253nM。随后，将化合物 7g 对接入 c-Met 蛋白中，并详细分析了结构-活性关系。这些发现表明，新型咪唑并吡啶衍生物化合物 7g 是一种有潜力的 c-Met 抑制剂，值得进一步研究用于癌症治疗。
