第 38 卷第 1 期Vol. 38 No. 1
2008 年 2 月Feb 2008
所属栏目：医药及中间体

4-色满酮芳环Mannich碱类化合物的合成及其抗血小板聚集活性研究
李慧媛1，张琳琳1，张传明1，刘晓平1，刘玉兰1，詹华强2，胡 春1 （1. 沈阳药科大学 制药工程学院，辽宁 沈阳110016；2.香港科技大学 生物系，香港）
摘　要：4-色满酮类化合物和色酮类化合物具有广泛的生物活性。笔者曾发现4-色满酮3位Mannich碱类化合物具有显著的抗血小板聚集活性，为了考察在4-色满酮的3-位Mannich碱类化合物中3-位胺甲基侧链是否为加强活性的必需基团，为确定其药效构象提供信息，笔者设计合成了4种4-色满酮芳环Mannich碱类化合物，同时又合成了3种色酮芳环Mannich碱类化合物。所合成的目标化合物均未见文献报道，其组成和结构经红外光谱、质谱和核磁共振氢谱确认。采用Born's比浊法对目标化合物进行了抗血小板聚集活性的体外筛选。实验结果表明，目标化合物对ADP和胶原诱导的家兔血小板聚集均具有显著的体外抑制活性。
关键词：4-色满酮；色酮；衍生物；合成；抗血小板聚集
中图分类号：R914　　文献标识码：A　　文章编号：1009-9212（2008）01- 0013-05
Synthesis and Anti-platelet Aggregative Activity of the Mannich Bases of 4-Chromanones and 4-Chromones
LI Hui-yuan1，ZHANG Lin-lin1，ZHANG Chuan-ming1，LIU Xiao-ping1，LIU Yu-lan1，ZHAN Hua-qiang2，HU Chun1 （School of Pharmaceutical Engineering，Shenyang Pharmaceutical University，Shenyang 110016，China；Department of Biology，The Hong Kong University of Science and Technology，Clear Water Bay，Hong Kong，China）
Abstract：4-Chromanones and chromones are known to exhibit a wide range of biological activities. Mannich bases at 3-position of 4-chromanones synthesized in our laboratory exhibit the significant anti-platelet aggregative activity. On the base of our previous work，the mannich bases at aromatic ring of 4-chromanones and chromones which were designed as the candidates of platelet aggregative inhibitors were synthesized as shown，the seven target compounds which were not reported in the literature were synthesized and characterized by 1H NMR，IR，LC-MS and GC-MS. The anti-platelet aggregative activity of the target compounds was tested using Born's method. According to screening results，some of the target compounds such as 7-hydroxy-8-（4-morpholinomethyl）-4-chromanone and 7-hydroxy-2，8-di（4-morpholinomethyl）chromone showed potent inhibitory activity against rabbit platelet aggregation induced by ADP in vitro，some of the target compounds such as 7-hydroxy-2，8-di（4-morpholinomethyl）chromone showed potent inhibitory activity against rabbit platelet aggregation induced by collagen in vitro.
Key words：4-chromanone；chromones；derivative；synthesis；anti-platelet aggregative
基金项目：国家自然科学基金资助项目（20472053）
作者简介：李慧媛（1977-），女，江苏徐州人，博士，从事多肽药物的设计与合成。
联 系 人：胡 春，教授，博士，博士生导师，从事新药设计与合成研究。（E-mail：chunhu1999@163.com）
收稿日期：2008-01-25