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

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

邹昊, 蒋皓, 周洁芸, 朱焰^*, 曹霖, 夏鹏, 张倩^*

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

收稿日期:2009-12-02 修回日期:2010-02-20 出版日期:2010-03-15 发布日期:2010-03-15
通讯作者: 朱焰*, 张倩*

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

Hao Zou, Hao Jiang, Jie-Yun Zhou, Yan Zhu^*, Lin Cao, Peng Xia, Qian Zhang^*

1. Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China
2. Department of Reproductive Pharmacology, Shanghai Institute of Planned Parenthood, Shanghai 200032, China

Received:2009-12-02 Revised:2010-02-20 Online:2010-03-15 Published:2010-03-15
Contact: Yan Zhu*, Qian Zhang*

摘要/Abstract

摘要： 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 (IC50 = 61.0 和 76.7 μM) 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: 新生血管抑制剂, 2-甲氧基雌二醇, 非甾体模拟物, 3-(4-羟基苯基)-4-甲基-6-甲氧基-7-羟基香豆素

Abstract: 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 anti-angiogenesis 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 μM, 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.

Key words: Angiogenesis inhibitor, 2-Methoxyestradiol, Non-steroidal analogue, 3-(4-Hydroxyphenyl)-4-methyl-6-methoxyl-7-hydroxycoumarin

中图分类号:

R916.41

Supporting:

Foundation item: National Natural Science Foundation (Grant No. 30500631).
^*Corresponding author. Tel.: 86-21-51980119

邹昊, 蒋皓, 周洁芸, 朱焰^*, 曹霖, 夏鹏, 张倩^*. 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[J]. .

Hao Zou, Hao Jiang, Jie-Yun Zhou, Yan Zhu^*, Lin Cao, Peng Xia, Qian Zhang^* . Synthesis of 3-(4-hydroxyphenyl)-4-methyl-6-methoxy-7-hydroxycoumarin and its analogues as angiogenesis inhibitors [J]. .