水杨酰芳胺类化合物的设计、合成及体外抗肿瘤活性研究  

Design, Synthesis, and Biological Evaluation of N-Aryl-salicylamide Derivatives as Potential Antitumor Agents

作　　者：王杰[1] 邬皓[1] 李家明[1] 许勤龙[1] 何广卫[2] 钟国琛[1] 张艳春[1] 

机构地区：[1]安徽中医学院药学院安徽省现代中药重点实验室,合肥230031 [2]合肥医工医药有限公司,合肥230059

出　　处：《有机化学》2013年第5期1026-1034,共9页Chinese Journal of Organic Chemistry

基　　金：安徽省自然科学基金(No.1208085MH128);国家创新药物孵化基地(No.2012ZX09401066)资助项目

摘　　要：根据骨架迁跃原理,设计并合成了一系列具有酪氨酸激酶抑制剂拉帕替尼(Lapatinib)和诺拉替尼(Neratinib)结构片段的水杨酰芳胺类化合物,其结构均经IR,1H NMR,13C NMR和MS确证.采用四甲基偶氮唑盐(MTT)法考察所合成化合物的体外抗肿瘤细胞(A549,MCF-7,SGC-7901,Bel-7402)活性.结果表明,所合成的化合物对4种肿瘤细胞增殖均有一定的抑制活性,部分化合物的活性强于阳性对照药吉非替尼(Gefitinib).According to the scaffold hopping, a series of N-aryl-salicylamide derivatives, which have fragments of tyrosine kinase inhibitors lapatinib and neratinib were designed and synthesized. Their structures were identified by IR, 1H NMR, 13C NMR and MS techniques. The target compounds were tested for cytotoxic activity against four cancer cell lines, including A549, MCF-7, SGC-7901, Bel-7402, by methyl thiazolyl tetrazolium （MTT） in vitro. All the compounds demonstrated certain antitumor abilities, and some of them were better than gefitinib.

关 键 词：水杨酰芳胺 酪氨酸激酶抑制剂 抗肿瘤 

分 类 号：TQ463[化学工程—制药化工]