目前在药物设计开发领域,5-HT_(2C)受体抑制剂备受关注,本文用比较分子相似性指数分析法(CoMSIA),研究34个二苯基取代吡咯烷酮类化合物的三维定量构效关系。考察衰减因子、电荷计算法以及不同作用场对构建模型的影响。建立的最佳模型交叉验证相关系数(q~2)为0.571,非交叉验证相关系数(R~2)为0.929,模型的标准偏差为0.225。发现疏水性在该类化合物与受体相互作用中发挥至关重要的作用,为进一步修饰结构提供指导。 At present, in the field of drug design and development, 5-HT 2C receptor inhibitors have drawn much attention. In this paper, the three-dimensional quantitative structure-activity relationship of 34 diphenyl substituted pyrrolidones was studied by comparative molecular similarity index analysis (CoMSIA) . The influence of attenuation factor, charge calculation method and different action fields on the model was investigated. The correlation coefficient (q ~ 2) of the best model was 0.571, the correlation coefficient (R ~ 2) of non-cross validation was 0.929, and the standard deviation of the model was 0.225. Hydrophobicity was found to play a crucial role in the interaction of such compounds with the receptor, providing guidance for further modification of the structure.