川芎嗪酯类衍生物的3D-QSAR研究  

3D-QSAR study of novel liqustrazine derivatives

作　　者：刘楠[1] 刘新泳[1] 

机构地区：[1]山东大学药学院,山东济南250012

出　　处：《中国药物化学杂志》2007年第5期283-287,313,共6页Chinese Journal of Medicinal Chemistry

基　　金：山东省科技发展计划项目(2006GG2202063);山东省1020工程计划项目(卫2004-15);济南市明星计划项目(200312)

摘　　要：目的建立预测模型,进行合理的药物设计和修饰。方法应用构象系统搜索程序确定23个2-取代酰氧甲基-3,5,6-三甲基吡嗪衍生物的可能活性构象,并以此活性构象为模板构建了这23个小分子化合物的三维结构,采用CoMFA及CoMSIA法对衍生物进行系统的三维定量构效关系分析。结果与结论CoMFA模型交叉验证系数q2=0.694,回归系数R2=0.994,SEE=0.023,F=376.924。CoMSIA模型交叉验证系数q2=0.657,回归系数R2=0.987,SEE=0.034,F=166.815。两种方法得到的构效关系模型都具有较好的预测能力。通过分析分子场等值面图在空间的分布,可以观察到叠合分子周围分子场特征对化合物活性的影响,为该类化合物进一步结构优化提供了有价值的参考。Aim To establish predictive models for future reasonable drug design and modification. Methods Pharmacophoric conformation of twenty-three novel 2-acyloxymethyl-3, 5, 6-trimethylpyrazine derivatives were determined by using system search programs, upon which 3D structures of the 23 molecules were modeled. Comparative molecular field analysis （CoMFA） and comparative molecular similarity indices analysis （CoMSIA） methods were employed to gain insight into the three dimensional quantitative structure activity relationships（3D-QSAR） of these derivatives systematically. Results and conclusion The coefficient of crossvalidation q^2 and non cross-validation R^2 for CoMFA model established by the study are 0.694 and 0.994 respectively and for CoMSIA model are 0. 657 and 0. 987. The results indicate that two models have good predictability. The resulting 3D contour maps provide valuable guidance for designing highly active compounds prior to their synthesis.

关 键 词：三维定量构效关系 比较分子场分析 比较分子相似性指数分析 川芎嗪酯类衍生物 

分 类 号：R284[医药卫生—中药学]