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p38α丝裂原活化蛋白激酶(p38αmitogen-activated protein kinase,p38αMAPK)是治疗类风湿关节炎的最有效的靶点之一,联苯酰胺是最近新发现的一类强效、高选择性的p38αMAPK抑制剂,本文运用比较分子力场分析(CoMFA)研究21个联苯酰胺类p38αMAPK抑制剂三维定量构效关系。建立CoMFA模型的交叉验证系数q~2=0.542,非交叉验证相关系数r~2=0.935,统计方差比F=43.136。预测训练集和测试集化合物活性,其值和实验值非常接近,表明模型的预测能力很好。模型显示立体场和静电场对生物活性的贡献分别为78.8%和21.2%。CoMFA模型的三维等值图可为化合物的结构改造提供理论依据。
p38α mitogen-activated protein kinase (p38αMAPK) is one of the most effective targets in the treatment of rheumatoid arthritis. Biphenyl amide is a newly discovered potent and highly selective p38α-MAPK inhibitor Agent, we used the comparative molecular force field analysis (CoMFA) to study the three-dimensional quantitative structure-activity relationship of 21 diphenylamide p38αMAPK inhibitors. The cross validation coefficient of establishing CoMFA model is q ~ 2 = 0.542, the correlation coefficient of non - cross validation is r ~ 2 = 0.935, and the statistical variance ratio is F = 43.136. The predicted training set and test set compound activity are very close to the experimental values, indicating that the model has good predictive power. The model shows that the contributions of stereo and electrostatic fields to bioactivity are 78.8% and 21.2% respectively. The three-dimensional contour of CoMFA model can provide a theoretical basis for the structural transformation of compounds.