靶向c-Met激酶小分子抑制剂的研究进展

Progress in small-molecule inhibitors of c-Met kinase

目的为进一步研究具有新颖结构的小分子c-Met激酶抑制剂提供参考。方法以"c-Met激酶"、"c-Met激酶抑制剂"、"酪氨酸激酶抑制剂"、"HGF/c-Met通路"、"构效关系"等为关键词,组合查询相关文献,对靶向小分子c-Met激酶抑制剂不同结构骨架的结构改造、构效关系进行综述。结果靶向小分子c-Met激酶抑制剂按结构骨架可分为喹啉类化合物、吡咯(噻吩)并吡啶(嘧啶)类化合物、吡啶类化合物、吲哚酮类化合物、三环类化合物及其他类化合物。总结此类化合物的结构改造和构效关系发现,除对c-Met激酶有显著抑制活性以外,还对其他靶点也表现出较好的抑制作用。结论 c-Met激酶已经成为抗肿瘤药物研究的一个重要靶点,对已进入临床研究的化合物进行结构改造和构效关系研究,为设计有效、低毒的小分子c-Met激酶抑制剂提供重要的借鉴作用,也加速了c-Met抑制剂类药物的开发进程。

Objective To provide a reference for the further study of small molecular c-Met kinase inhibitors with novel structures.Methods The structural modification and structure-activity relationship of different structural skeletons of c-Met kinase inhibitors targeting small molecules were reviewed by querying related documents with keywords'c-Met kinase','c-Met kinase inhibitors','tyrosine kinase inhibitors','HGF/c-Met pathway','structure-activity relationship',etc.Results C-Met kinase inhibitors targeting small molecules could be divided into the quinoline compounds,pyrrolopyridine or(-thieno)pyridine or(-thieno)pyrimidine compounds,pyridine compounds,indole ketone compounds,triclic compounds and other classes compounds according to their structural framework.The structural modification and structure-activity relationship of these compounds were summarized.It was found that in addition to the significant inhibitory activity of c-Met kinase,they also exhibited good inhibitory effects on other targets.Conclusion C-Met kinase has become an important target in the study of antitumor drugs.The study of the structural modification and structure-activity relationship of those compounds in clinical research can provide reference to the design of an effective and low-toxic small molecule c-Met kinase inhibitor.Meanwhile,it also accelerates the development for c-Met inhibitor drugs.