物理化学学报 >> 2005, Vol. 21 >> Issue (11): 1259-1263.doi: 10.3866/PKU.WHXB20051113

研究论文 上一篇    下一篇

毒蕈碱受体激动剂的三维定量构效关系研究

朱军; 牛彦; 吕雯; 雷小平   

  1. 北京大学药学院药物化学系, 北京 100083
  • 收稿日期:2005-04-20 修回日期:2005-06-13 发布日期:2005-11-15
  • 通讯作者: 雷小平 E-mail:leixp@bjmu.edu.cn

Studies on Three-dimensional QSAR of Muscarinic Receptor Agonists

ZHU Jun; NIU Yan; LÜ Wen; LEI Xiao-ping   

  1. School of Pharmaceutical Sciences, Peking University, Beijing 100083
  • Received:2005-04-20 Revised:2005-06-13 Published:2005-11-15
  • Contact: LEI Xiao-ping E-mail:leixp@bjmu.edu.cn

摘要: 采用比较分子场分析法(CoMFA)研究了55个四氢吡啶类毒蕈碱受体激动剂的三维定量构效关系(3D-QSAR), 建立了具有较强预测能力的3D-QSAR模型. 所得模型的交叉验证相关系数(q2)为0.507, 常规相关系数(R2)为0.982 , 标准方差为0.218, 说明系列化合物分子周围立体场和静电场的分布与生物活性间存在良好的相关性. 模型不仅很好地预测了训练集和测试集化合物的活性, 而且为设计活性更高的受体激动剂提供了理论依据.

关键词: M1受体, 激动剂, 比较分子场分析法, 构效关系

Abstract: Three dimensional structure-activity relationship of 55 muscarinic receptor agonists were studied using comparative molecular field analysis (CoMFA) technique. The relationship between the activities and structures was significant with cross-validated value (q2), non-cross-validated value (R2) and standard error of estimate (SEE) of 0.507, 0.982 and 0.218, respectively. The result indicated that there is a good correlation between the distribution of molecular steric and electrostatic field and bioactivity. This model can not only well predict the activity of the compound in the training set and test set, but also contribute to gain further insights into the requirements for potential agonists and rational design of novel molecules based on the CoMFA contour plots.

Key words: M1 receptor, Agonists, CoMFA, Quantitative structure-activity relationships(QSAR)