Synthesis of 3-(4-hydroxyphenyl)-4-methyl-6-methoxy-7-hydroxycoumarin and its analogues as angiogenesis inhibitors  

新生血管抑制剂3-(4-羟基苯基)-4-甲基-6-甲氧基-7-羟基香豆素及其类似物的合成研究(英文)

作　　者：邹昊[1] 蒋皓[1] 周洁芸 朱焰 曹霖 夏鹏[1] 张倩[1] 

机构地区：[1]复旦大学药学院药物化学教研室,上海201203 [2]上海计划生育研究所生殖药理研究室,上海200032

出　　处：《Journal of Chinese Pharmaceutical Sciences》2010年第2期136-140,共5页中国药学（英文版）

基　　金：National Natural Science Foundation(Grant No. 30500631).

摘　　要：3-（4-Hydroxyphenyl）-4-methyl-6-methoxy-7-hydroxycoumarin （2a） and its analogues with different substituents at the p-position of 3-phenyl group were designed and synthesized as the non-steroidal analogues of 2-methoxyestradiol （2-ME 1）. The desired compounds were synthesized via a novel and simple route and the effects of specific substituents on their antiangiogenesis activities were investigated with Human umbilical vein endothelial cells （HUVECs） proliferation assays. Preliminary biological screening showed that compounds 2a and 2d （IC50 = 61.0 and 76.7 ktM, respectively） have potential anti-angiogenesis activities. The bulk of the group at the p-position of 3-phenyl group likely play an important role in their activities.为探索新生血管抑制剂2-甲氧基雌二醇的非甾体模拟物,首先设计并合成了3-(4-羟基苯基)-4-甲基-6-甲氧基-7-羟基香豆素(2a),并通过一条简易方便的路线进一步完成了2a 3-苯环对位含不同取代基的类似物的合成,以研究该类化合物的新生血管抑制活性以及该特殊位点对活性的影响。初步的生物活性测定显示,化合物2a和2d(IC_(50)=61.0和76.7μM)对人脐静脉内皮细胞(HUVECs)具有抑制活性,同时该类化合物3-苯环对位上取代基团体积的大小对生物活性有着重要影响。

关 键 词：Angiogenesis inhibitor 2-METHOXYESTRADIOL Non-steroidal analogue 3-（4-Hydroxyphenyl）-4-methyl-6-methoxyl-7- hydroxycoumarin 

分 类 号：R914[医药卫生—药物化学]