表皮生长因子受体酪氨酸激酶抑制剂的药效团研究-上海有机化学研究所.pdfVIP

2003 年第 61 卷 化 学 学 报 Vol. 61 , 2003 第 3 期 , 430～434 ACTA CHIMICA SINICA No. 3 , 430 ～434 ·研究简报· 表皮生长因子受体酪氨酸激酶抑制剂的药效团研究 彭　涛　　裴剑锋　　周家驹 ( 中国科学院过程工程研究所 　北京 100080) 摘要 　根据一系列表皮生长因子受体酪氨酸激酶抑制剂的三维定量构效关系研究 ,得到了该类抑制剂的药效团 ,研究结果 与Novartis 的药效团模型相当类似. 药效团包括一个氢键受体 ,一个氢键给体 ,一个疏水区和一个带有氯或溴原子的苯环. 该药效团对于研究表皮生长因子受体酪氨酸激酶抑制剂结构与活性的关系具有重要的意义. 通过三维数据库搜索可能会 得到新的先导化合物. 关键词 　药效团 ,表皮生长因子受体 ,酪氨酸激酶抑制剂 ,活性位点 Pharmacophore Analysis of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors PEI , JianFeng 　　ZHOU , JiaJu PENG, Tao 　　 ( ) Institute of Process Engineering , Chinese Academy of Sciences , Beijing 100080 Abstract 　A threedimensional pharmacophore of epidermal growth factor receptor tyrosine kinase inhibitors was obtained based upon 3DQSAR of a series of these inhibitors. The result was accordant with the pharmacophore model given by the scientists at Novartis. The pharmacophore included a hydrogen bond receptor , a hydrogen bond donor , a hydrophobic area and a phenyl ring with a chlorine or a bromine atom. This pharmacophore is very useful for clarifying the structureactivity relationships of EGFR tyrosine kinase inhibitors. Some lead compounds may be acquired through threedimensional database searching. Keywords 　pharmacophore , EGFR , tyrosine kinase inhibit