新型二芳基甲烯基环烷烃衍生物的合成及抗肿瘤活性研究  

Synthesis and antitumor activity of novel diarylmethenecycloalkane derivatives

作　　者：刘宗英[1,2] 高岩[2] 金洁[2] 李卓荣[2] 

机构地区：[1]国家食品药品监督管理总局药品审评中心,北京100038 [2]中国医学科学院北京协和医学院医药生物技术研究所,北京100050

出　　处：《中国新药杂志》2016年第16期1898-1902,共5页Chinese Journal of New Drugs

基　　金：国家自然科学基金资助项目(30901840)

摘　　要：目的:设计合成新型二芳基甲烯基环烷烃衍生物并测定其体外抗肿瘤活性。方法:以3,4,5-三甲氧基苯甲酰氯(3)为起始原料,经傅克酰基化、Mcmurry偶联反应得到目标化合物1a-f;以取代的4-甲氧基苯甲醛(7a-b)为起始原料,经亲核加成、氧化、Mcmurry偶联反应得化合物2a,11b;11b经脱硅醚保护得到化合物2b。结果:共合成8个二芳基甲烯基环烷烃衍生物,其结构均经核磁共振氢谱和高分辨质谱确证;其中4个化合物(1a-b,2a-b)的体外抗人乳腺癌细胞MCF-7的活性相当于考布他丁A-4(CA-4)。结论:化合物1a-b,2a-b的体内抗肿瘤活性值得进一步研究。Objective： To synthesize novel diarylmethenecycloalkane derivatives and evaluate their antitumor activities. Methods： Compounds 1a-f were synthesized via Friedel-Crafts reaction and Mcmurry reaction using 3,4,5-trimethoxybenzoyl chloride（ 3） as a starting material. Substituted 4-methoxybenzaldehyde（ 7a-b） was used as a starting material,after nucleophilic addition,oxidation,and Mcmurry reaction to yield 2a and 11 b,2b was then synthesized via desilylation of 11 b. Results： The structures of 8 diarylmethenecycloalkane derivatives synthesized in this study were confirmed by^1H-NMR and HRMS. Four compounds（ 1a-b,2a-b） showed similar antitumor activity against human breast cancer MCF-7 cells to that of combretastatin A-4（ CA-4）. Conclusion： The in vivo antitumor activity of compounds 1a-b,2a-b is deserved to further investigation.

关 键 词：二芳基甲烯基环烷烃衍生物 血管生成抑制剂 抗肿瘤活性 合成 

分 类 号：R914.5[医药卫生—药物化学]