【摘要】 目的本文针对51个具有CCR5拮抗剂作用的咪唑并吡啶衍生化合物进行构效关系研究,希望能够为设计此类小分子药物提供依据。方法运用比较分子力场分析(Co MFA)和比较分子相似性指数分析(Co MSIA)这2种经典的三维定量构效关系(3D-QSAR)方法,分别建立了相应的模型,进行分子结构和抗病毒活性彼此关系的分析。结果 Co MFA模型的交叉验证系数q~2和相关系数r~2分别为0.617和0.825,立体场和静电场对活性的贡献为62%和38%;Co MSIA模型的交叉验证系数q~2和相关系数r~2分别为0.599和0.810,立体场、静电场、疏水场、氢键供体场和受体场对活性的贡献分别为9.8%、12.5%、33.8%、30.8%和13.1%。结论这2种模型都显示出了较好的预测性和稳定性,其三维等势图也证实了这些化合物拮抗CCR5的构效关系。更多还原

【Abstract】 The CC chemokine receptor 5(CCR5) has been identified as a critical determinant in the pathwayof infection and inflammation of HIV-1,which makes it an attractive target for anti-HIV drugs design.In this work,comparative molecular field analysis(Co MFA) and comparative molecular similarity indices analysis(Co MSIA) wereperformed on a group of 51 CCR5 antagonistic derivatives,and the Co MFA and Co MSIA models were built for thethree-dimensional quantitative structure-activity relationship(3D-QSAR) analyses.The coefficients ofcross-validation q~2 and non cross-validation r~2 for Co MFA model were 0.617 and 0.825(S%=0.617,E%=0.825),forCo MSIA model were 0.559 and 0.810 respectively(S%=9.8%,E%=12.5%,H%=33.8%,D%=30.8%,A%=13.1%).Both of the two models display enough predictive ability and stability,and their contour maps also demonstrate thestructure-activity relationship of the compounds.更多还原