拉帕替尼类似物的合成及抗肿瘤活性研究  

Synthesis and Antitumor Activity of New Lapatinib Derivatives

作　　者：刘娟[1] 张娅玲[1] 张喜全 顾红梅[2] 李宝林[1] 

机构地区：[1]陕西师范大学化学化工学院,药用资源与天然药物化学教育部重点实验室,西安710062 [2]正大天晴药业集团股份有限公司,南京210038

出　　处：《化学通报》2016年第4期360-365,共6页Chemistry

基　　金：国家自然科学基金项目(21272144)资助

摘　　要：以N’-（2-氰基-4-碘苯基）-N,N-二甲基甲脒为原料,经过Dimroth重排反应、Suzuki偶联、还原氨化3步反应合成了4种新型的拉帕替尼类似物。借助NMR、IR和HRMS对反应中间体和目标化合物进行结构表征,并采用MTT法在SW480、A549和A431人肿瘤细胞上进行了这些化合物抗肿瘤活性的初步体外评价。结果表明,以上4种化合物均具有明显的抑制肿瘤细胞生长作用,特别是化合物5a对所试肿瘤细胞均表现出良好的生长抑制活性（IC50：5.78~13.38μmol/L）,与临床使用的抗肿瘤药物拉帕替尼的活性（IC50：4.80~14.90μmol/L）相当。Four new lapatinib derivatives were prepared using N’-（ 2-cyano-4-iodophenyl）-N,N-dimethylformamidine as the starting material by Dimroth rearrangement,Suzuki coupling,reductive amination in turn. The structures of the reaction intermediates and target compounds were characterized with the NMR,IR and HRMS. The antitumor activities of these compounds on SW480,A549 and A431 tumor cells were tested preliminarily by the MTT method in vitro experiment. The results indicated that they had significant inhibition on the growth of tumor cells,especially compound 5a showed good growth inhibitory activity on all the test cells（ IC50： 5. 78 ~ 13. 38μmol/L）which is similar as that of lapatinib（ IC50： 4. 80 ~ 14. 90μmol/L）.

关 键 词：拉帕替尼 抗肿瘤活性 合成 

分 类 号：TQ463[化学工程—制药化工]