192取代雄烯二酮芳构酶抑制剂的定量构效关系研究.pdfVIP

2002 年第 60 卷 化 学 学 报 Vol. 60 , 2002 第 10 期 , 1784～1788 ACTA CHIMICA SINICA No. 10 , 1784 ～1788 19取代雄烯二酮芳构酶抑制剂的定量构效关系研究 a , b a a , b a 许辽萨 　　何严萍 　　李振华 　　王文宁 范康年 , a , b 　　陈芬儿 , a ( a b ) 复旦大学化学系 　 理论化学物理中心 　上海 200433 摘要 　用分子动力学和量子化学 AM1 经验方法对系列 19位取代的雄烯二酮芳构酶抑制剂的定量构效关系进行了 研究 ,结果表明该位置的取代基必须符合 P450 芳构酶活性位点的立体效应和疏水作用的要求. 此类化合物作为较 好的电子供体与芳构酶结合 ,给电子的主要基团为 21位含 S 取代基. 这些研究结果为设计活性更高的芳构酶抑制 剂提供了有益的参考信息. 关键词 　芳构酶抑制剂 ,雄烯二酮 ,定量构效关系 ,AM1 ,分子动力学 QSAR of 19Substituted Androstenedione Analogs as Aromatase Inhibitors XU , LiaoSa a , b 　　HE , YanPing a 　　LI , ZhenHua a , b 　　WANG, WenNing a , b FAN , KangNian , a , b 　　CHEN , FenEr , a ( a Department of Chemistry , b Centerfor Theoretical Chemical Physics , Fudan University , Shanghai 200433) Abstract 　The quantitative structureactivity relationship (QSAR) of a series of 19substituted androstenedione analogs as aromatase inhibitors was investigated by molecular dynamics and quantum chemical AM1 method. The results show that there are spatial requirement and hydrophobic effect in the interaction between P450 aromatase and 19substituted inhibitors. The results also show that most of these compounds are excellent electron donors , and the main electron donating group of the compounds is around the sulfur atom of 21 position. These results may provide valuable clues for searching potential aromatase inhibitor