7-芳杂环高喜树碱的合成与抗肿瘤活性研究  

Synthesis and antitumor activity of 7-heteroaromatic homocamptothecin derivatives

作　　者：缪震元[1] 张万年[1] 游亮[1] 郭巍[1] 张晶[1] 盛春泉[1] 姚建忠[1] 车晓颖[1] 王文雅[1] 

机构地区：[1]第二军医大学药学院,上海200433

出　　处：《中国药物化学杂志》2008年第2期105-108,共4页Chinese Journal of Medicinal Chemistry

基　　金：上海市科委重点科技攻关项目(064319009)

摘　　要：目的设计并全合成7-芳杂环高喜树碱衍生物并测试抗肿瘤活性。方法首先合成关键中间体5-乙基-5-羟基-4,5,8,9-四氢氧杂环庚三烯并[3,4-f]中氮茚-3,7,11(1H)-三酮,经Frilander反应得到7-氯甲基-10-甲基高喜树碱,然后与芳杂环生成目标产物。结果与结论合成了3个新化合物,化合物的结构经1H-NMR、FAB-MS谱确证,体外抗肿瘤活性测试结果显示化合物7和8c对肿瘤细胞A549、LOVO和MCF-7具有良好的抗肿瘤活性,优于拓扑替康。Aim To design and synthesize 7-heteroaromatic homocamptothecin derivatives to screen more potent antitumor agents. Methods The target compounds were synthesized by Frilander condensation from heteroaromatic compounds and 7-chloromethyl homocamptothecin（7） which was obtained from 5-ethyl-5- hydroxy-4,5, 8, 9-tetrahydrooxocycloheptatriene- [ 3, 4-f ]-indolizin-3, 7, 11 （ ^1H ）-trione （6）. Results and conclusion Three new compounds were synthesized and their structures were characterized by ^1H-NMR and FAB-MS. Antitumor activity tests in vitro indicated that compound 7 and 8c possessed higher inhibiting activity against A-549, LOVO and MCF-7 cell lines than topotecan.

关 键 词：高喜树碱 合成 抗肿瘤活性 

分 类 号：R914[医药卫生—药物化学] R730.5[医药卫生—药学]