取代基物化参数用于2-苯基吲哚衍生物构效关系的研究

QSAR Studies of 2-Phenylindole Derivatives Using Physicochemical Parameters of Substituents

用取代基电性、立体性和疏水性物化参数对2-苯基吲哚衍生物进行了结构表征,并对化合物与雌激素受体相对亲和力进行定量结构活性相关(QSAR)研究。经逐步回归筛选变量后,所建多元线性回归方程的复相关系数R2及留一法交互检验相关系数R2cv分别为0.900和0.662。用预测集样本进行了外部预测,所得外部预测样本集复相关系数Re2xt和外部预测集交互检验Q2ext分别为0.896 6和0.897 4。模型结果显示:吲哚环1号N原子上立体效应强的取代基有利于亲和力的提高;而吲哚环1号N原子和3号C原子上电性强的取代基、2-苯基环上4′号位置有羟基取代等,均对化合物亲和力的提高不利。

A novel substituent descriptor based on the physicochemical parameters about the electronic, hydrophobic and steric properties of substituents is used to describe the chemical structures of 2- phenylindole derivatives. The variables are reduced using stepwise multiple regression （SMR） method for the training set, and the statistical results indicate that the correlation coefficient square in the multiple linear regression and cross validation using leave one out （LOO） is 0. 900 and 0. 662, respectively. To validate the predictive power of resulting models, external validation are performed with Rext^2 and Qext^2 values of 0. 896 6 and 0.897 4, respectively. The models obtained also shows that the substituents on nitrogen atom of the 1-position of the indole ring have more relative binding affinities. But introduction of substituents with strong electronic effects in 1 and 3 positions of the indole ring and the structure with hydroxy group at in the 4＇ position of 2-phenyl ring may decrease the binding affinity between the 2-phenylindole derivatives and ligand of estrogen receptor.