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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。
Aim To investigate the structure-activity relationship of 51 imidazopyridine derivatives with CCR5 antagonists, we hope to provide a basis for the design of such small molecule drugs. Methods Two classic 3D QSAR methods, Co MFA and Co MSIA, were established respectively to establish the corresponding models for molecular structure and molecular structure analysis Antiviral activity of the relationship between the analysis. Results The cross validation coefficient q ~ 2 and the correlation coefficient r ~ 2 of the Co MFA model were 0.617 and 0.825, respectively, and the contribution of stereo and electrostatic fields to the activity was 62% and 38% respectively. The cross validation coefficients of the Co MSIA model were q ~ 2 and The correlation coefficients r ~ 2 were 0.599 and 0.810, respectively. The contributions of three-dimensional field, electrostatic field, hydrophobic field, hydrogen donor donor site and acceptor field were 9.8%, 12.5%, 33.8%, 30.8% and 13.1% respectively. Conclusions Both models show good predictability and stability. The 3-D isosteres also confirm that these compounds antagonize the structure-activity relationship of CCR5.