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目的:通过构建噻嗪类11β-羟类固醇脱氢酶(11β-HSD)抑制药的三维定量构效关系(3D-QSAR)模型,用于其结构改造及发现具有更高生物活性的11β-HSD抑制药.方法:基于骨架叠合的模式,采用比较分子力场分析(CoMFA)的方法,构建噻嗪类衍生物定量构效关系模型,并用分子对接的方法对已构建的3D-QSAR模型进行验证.结果:得到了高精度的11β-HSD抑制药的3D-QSAR模型(CoMFA:q2=0.346,r2=0.850;其中q2为交叉验证系数,r2为非交叉验证系数).结论:本文构建的3D-QSAR模型可为11β-HSD抑制药骨架各个位点的化学修饰,实施定向合理设计,为开发新型抗2型糖尿病药物提供理论基础.“,”Objective:To establish a three-dimensional quantitative structure-activity relationship (3D-QSAR) model for thiazide 11β-hydroxy steroid dehydrogenase ( HSD) inhibitors in order to perform structure modification and find thiazide 11β-HSD inhibitors with more activity. Methods: The 3D-QSAR model of thiazine derivatives was constructed by the method of comparative molecular force field analysis, and the model was validated by using a molecular docking method. Results:An accurate 3D-QSAR model of 11β-HSD inhibitors was obtained (CoMFA:q2 =0. 346, r2 =0. 850, where q2 was the cross-validation coefficient and r2 was the non-cross validation coefficient) . Conclusion:The results provide important theoretical basis for the rational design of novel thiazide 11β-HSD inhibitors.