应用CoMFA及CoMSIA方法研究氮杂环类CCR5拮抗剂的三维定量构效关系

3D-QSAR Studies of Azacycles CCR5 Antagonists Using CoMFA and CoMSIA Methods

采用比较分子场分析(CoMFA)和比较分子相似性指数分析(CoMSIA)的方法研究氮杂环类CC趋化因子受体5(CCR5)拮抗剂的三维定量构效关系(3D-QSAR),并建立了相应的3D-QSAR模型。结果表明:采用这2种方法建立的3D-QSAR模型对该类化合物具有良好的预测能力(CoMFA:交叉验证系数q^2=0.644,相关系数r^2=0.974;CoMSIA:交叉验证系数q^2=0.553,相关系数r^2=0.822)。根据等值面图分析得出:氮杂环类CCR5拮抗剂的疏水基团及强吸电子基团可以增强其抗病毒活性,有助于设计活性更好的氮杂环类CCR5拮抗剂。

The three-dimensional quantitative structure-activity relationship （3D-QSAR） models of azacyles CCR5 antagonists were developed using comparative molecular field analysis （CoMFA） and comparative molecular similarity indices analysis （CoMSIA） methods. The 3D-QSAR models were shown to have excellent prediction （ CoMFA ： the cross-validation coefficient q^2 = 0. 644, and the correlation coefficient r^2 = 0. 974, CoMSIA： the cross-validation coefficient q^2 = 0. 553, and the correlation coefficient r^2= 0. 822）. 3D contour maps suggested that hydrophobic substituents and electron- withdrawing groups on the core part would decrease antiviral activity. This study may help to design novel selective antagonists of CCR5 with desired activity.