γ-羟基丁烯羟酸内酯类内皮激素拮抗剂的比较分子场分析

Comparative Molecular Field Analysis of γ-Hydroxy Butenolide Endothelin Antagonists

采用比较分子场分析方法 ( Co MFA)分析了一组 γ-羟基丁烯羟酸内酯类内皮激素拮抗剂的活性与结构的关系 .在计算中 ,除了考察立体场和静电场 ,还引入了氢键场 ,结果表明 ,引入氢键场可以明显改善计算的结果 .所得模型不仅能够很好地预测训练集中的分子 ,而且还可准确地预测测试集中的化合物 .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的立体、静电以及氢键特征对化合物活性的影响 .

Three dimensional structure activity relationships of γ hydroxy butenolide endothelin antagonists were studied using CoMFA technique. Besides the steric and the electrostatic fields, the H bond field was introduced into the computations. The QSAR results showed that the introduction of the H bond field improved the quality of the obtained CoMFA model obviously. The model can forecast not only the compounds in the training set but also the compounds in the test set. The CoMFA contour plots identified several key features including steric, electrostatic and H bond fields, which were valuable for us to get insight into the potential mechanisms of the intermolecular interactions between inhibitor and receptor. Suitable steric and electrostatic effects as well as H bond donor and acceptor are required for a higher activity.