二芳基咪唑类化合物选择性环氧合酶-2(COX-2)抑制性的QSAR研究

A QSAR study of 1,2-diarylimidazole cyclooxygenase-2 inhibitors

应用HyperChem7.0计算与二芳基咪唑类化合物选择性环氧化酶(COX-2)的抑制性相关的量化参数以及自己设计的结构编码参数,对52种1,2-二芳基咪唑化合物的抑制性做QSAR研究。使用逐步回归筛选出影响抑制性的主要参数分子偶极矩μ、分子疏水参数logP和编码参数R_2、R_5和R_7建立QSAR方程。经留三法验证,检验结果相关系数R为0.9155,剩余标准偏差s为0.3601,与回归拟合得到的R=0.9357,s=0.3157接近,表明所建QSAR方程预测效果较好,稳定性较高。对筛选参数的分析表明,μ、logP主要通过影响化合物的脂溶性,R_2、R_5通过影响化合物的空间结构,R_7则通过化合物与COX-2对应活性位点氢键作用的变化,分别对化合物对COX-2的抑制性产生影响。

The quantitative structure activity relationship（QSAR）of 52 1,2-diarylimidazole inhibitors is set up with some quantum-chemical parameters calculated by HyperChem 7.0 students and self-designed structure descriptor codes.The quantum-chemical parameters（μ and logP）and the structure descriptors code（R2,R5,and R7）are selected by stepwise regression.The predicting model has a correlation coefficient（R）of 0.9357 and residual standard error（s）of 0.3157.The performance of the QSAR equation is tested by leave-three-out procedure（LTO）,and the correlation coefficient R and standard error（s）are 0.9155 and 0.3610 respectively.It shows that the QSAR model has good stability and predictability.The study indicates that the parameters（μ,logP ）influence the in hibitor of the compound in fat-soluble,the parameters（ R2,R5）influence the inhibitor of the compound in space effect and the param eters（R7）influence the inhibitor of the compound by hydrogen bond action between the active site of cyclooxygenase-2 and compound.