己烷雌酚衍生物定量构效关系的研究

应用分子力学方法MM 和半经验量子化学AM1法几何全优化得到20个己烷雌酚衍生物的优势构象,再利用量子化学算法和分子图形学技术获得电子结构参数和几何结构参数,采用多元逐步回归分析和人工神经网络误差反传算法(BP)研究衍生物与雌激素受体相对亲和力的QSAR.结果表明:分子最低空轨道能、7号碳原子和10号碳原子间键长有利于提高亲和力;而引入大体积取代基对化合物亲和力的提高不利,建立了20个己烷雌酚衍生物的构效关系式,所建方程的相关系数及去一法交互检验复相关系数分别为0.963和0.880.

Study on quantitative structure-activity relationship of hexestrol derivatives

To analyze the QSAR of 20 hexestrol derivatives,MM~ molecular mechanics method and semi-empirical AM~1 method had been performed.Using multivariate linear regression analysis(MLR)and standard back-propagation algorithm of artificial neural net- work(BP),we obtained a significant QSAR.The model obtained also showed that the relative binding affinities increased with the in- crease of the energy of the lowest unoccupied orbit and the bond length of C_7 between C_(10).But introduction of substituents with big vol- ume may decrease the binding affinities between the hexestrol derivatives and estrogen receptor.The correlation coefficient and cross validation using leave one out(LOO)of successful QSAR with correlation for 20 hexestrol derivatives were 0.963 and 0.880.