二氢吡啶类化合物的三维定量构效关系

Three Dimensional Quantitative Structure-activity Relationship of Dihydropyridine Derivatives

通过分子力学和量子化学计算,得出两种二氢吡啶衍生物的低能构象,再应用比较分子力场分析方法(CoMFA)和比较分子相似性指数分析方法(CoMSIA)分别对两种构象的43个二氢吡啶衍生物进行3D-QSAR研究.计算结果表明,用两种方法建立的两种构象的构效关系模型均有较好的预测能力.通过分析CoMFA和CoMSIA的系数等势图,直观地了解二氢吡啶衍生物的结构对生物活性的影响,为进一步设计高活性的二氢吡啶衍生物提供一定的理论依据.

Two minimum energy conformations of DHPs were obtained by molecular mechanics and quantum chemistry calculation. In the studies of 3D-QSAR, comparative molecular fields analysis (CoMFA) and comparative similarity indices analysis (CoMSIA) were applied using a data set of 43 DHPs of two-conformations. The results indicate that the models of two-conformations, investigated by the two kinds of 3D-QSAR techniques, are significant and have good predictability. The analysis of steric and electrostatic CoMFA and CoMSIA coefficients contour maps reveals the influence of the structures on biological activity and gives insights to the further design of highly active DHPs compounds.