3-取代吲哚-2-酮类化合物的设计、合成及抗肿瘤活性研究  

Design,synthesis and anti-tumor activities in vitro of novel 3-substituted indolin-2-one compounds

作　　者：周浩[1] 周峰[1] 周有骏[1] 

机构地区：[1]第二军医大学药学院药物化学教研室,上海200433

出　　处：《药学实践杂志》2015年第2期131-133,142,共4页Journal of Pharmaceutical Practice

基　　金：国家自然科学基金(21172260)

摘　　要：目的设计合成对微管蛋白和血管内皮细胞生长因子受体2(VEGFR-2)激酶具有双重抑制作用的3-取代吲哚-2-酮类化合物,考察其体外抑瘤活性。方法以取代的苯胺为起始原料,经缩合、环合、还原、取代等反应制得系列目标化合物,并考察该系列化合物对微管蛋白和肿瘤细胞的抑制活性。结果共合成了11个新的目标化合物。实验结果显示,化合物j9对微管蛋白和VEGFR-2激酶具有双重抑制活性。所有目标化合物对3种肿瘤细胞株均有中等强度的抑制活性。结论该类化合物是一类具有多靶点作用的抗肿瘤化合物。Objective To compose and evaluate anti‐tumor activities of 3‐substituted indole‐2‐one compounds which may have dual inhibitory activities against both tubulin protein and VEGFR‐2 tyrosine kinase .Methods Target compounds were prepared starting from substituted aniline viacondensation ,cyclization and reduction .Results 11 target compounds were syn‐thesized and all the compounds displayed moderate anti‐proliferative activities against three tumor cell lines .Compound j9 showed a certain inhibitory activity against both VEGFR‐2 kinase and tubulin protein in vitro .Conclusion This series of indo‐lin‐2‐one derivatives were found to be a novel kind of multi‐target inhibitor .

关 键 词：血管靶向药物 3-取代吲哚-2-酮类化合物 微管蛋白抑制活性 激酶抑制活性 

分 类 号：R916.1[医药卫生—药学]