新型酪氨酸激酶小分子抑制剂的三维药效团研究  

Pharmacophore Model Analysis of Novel Tyrphostins

作　　者：廖宁[1] 侯廷军[1] 陈丽蓉[1] 徐筱杰[1] 

机构地区：[1]北京大学化学与分子工程学院,北京100871

出　　处：《计算机与应用化学》2000年第1期37-38,共2页Computers and Applied Chemistry

基　　金：国家自然科学基金! ( 2 9873 0 0 3 )资助项目

摘　　要：对受体酪氨酸激酶 (RTK)的药物抑制对控制恶性肿瘤具有重要意义。最近发现的苄叉丙二腈化合物家族对RTK中的HER2受体具有较强的抑制作用。本文对这一系列化合物进行了柔性的三维药效团分析 ,得到了一个预测能力很好的药效团模型 ,线性回归系数R =0 .958。这个模型对于研究此类化合物的结构与活性关系 ,以及评估此类未知化合物活性具有重要作用。Receptor tyrosine kinases (RTKs) have been shown to play a crucial role in the cellular signal transduction pathways. The overexpress of RTKs caused cellular proliferation have close relationship with malignant tumor development. A novel molecule family selectively inhibit HER2 receptor, one of the PTKs, were found recently. Flexible pharmacophore research was performed on this group of tyrophostins in this study. A common pharmacophore model was generated and regressed within the ensemble of 19 active compounds. The pharmacophore model shows great correlate coefficient (R = 0 958) and high forcast ability. The model proved to correctly represent the 3D factors affect the tyrphostins' biological activity.

关 键 词：药效团 酪氨酸激酶 苄叉丙二腈 结构 生物活性 

分 类 号：O626[理学—有机化学] R962[理学—化学]