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对33个喹啉衍生物的雌激素β受体活性进行了分子对接以及比较分子力场分析(CoMFA)和比较分子相似性指数分析(CoMSIA).研究发现对接得分与亲合活性pIC_50具有显著的线性相关关系.进一步分析表明:色烷环与喹啉环上的羟基与受体间的氢键作用,样本与受体口袋的疏水作用,以及样本与受体Arg346和Giu305残基间的静电作用是影响亲合活性的主要因素.此外,样本喹啉环上取代基的空间位阻作用亦对活性有重要影响.根据对接后的优势构豸将33个样本进行叠合并进行CoMFA与CoMSlA研究,其中以选用立体场、静电场、疏水场和氢键供体场建立自CoMSIA模型结果最优,其主成分,r~2,q~2(LOO)和r_pred~2分别为6,0.958,0.669和0.741.三维等势图分析结果与对接分析结果基本一致.“,”The molecular docking followed by comparative molecular field analysis (CoMFA) and com-parative molecular similarity index analysis (CoMSIA) was employed to the three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of estrogen receptor-β of 33 quinoline derivatives. A sig-nificant correlation coefficient was obtained between total scores and binding affinities. The results showed that the hydrogen-bonding interactions between the hydroxy group of chromane and quinoline ring and the receptor, hydrophobic interactions between the ligand and the active site of estrogen receptor-β, and elec-tronic interactions between the ligand and the Arg346 and Glu305 residuals were the dominant factors af-fecting the binding affinities. Besides, the steric effect of substituting group of quinoline ring also affected the binding activities. Based on the docking conformations, CoMFA and CoMSIA were employed to the QSAR studies of 33 quinoline derivatives. The number of principal components, r~2, q~2 (leave-one-out, LOO), r_pred~2 of the optimal CoMSIA model were 6, 0.958, 0.669 and 0.741 respectively. The conclusions obtained from contour map analysis were in agreement with the docking results.