含呋喃环双酰脲类衍生物的三维定量构效关系研究

采用比较分子力场分析法(CoMFA)和比较分子相似性指数分析法(CoMSIA), 对27个新型双酰基脲类化合物的杀蚊幼虫(Aedes aegypti L.)活性进行三维定量构效关系(3D-QSAR)研究. 在CoMFA研究中, 考察了网格点步长对统计结果的影响. 在CoMSIA研究中, 系统考察了各种分子场组合、网格点步长和衰减因子对模型统计结果的影响, 发现立体场和氢键供体场的组合得到最佳模型. 所建立的CoMFA和CoMSIA模型的非交叉验证相关系数r2值分别为0.828和0.841, 并都具有较强的预测能力. CoMFA和CoMSIA模型的三维等值图不仅直观地解释了结构与活性的关系, 而且为后续优化该系列化合物提供了理论依据.

3D-QSAR Studies on Diacylurea Derivatives Containing Furan Moiety

Comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) were applied to the study of the three-dimensional quantitative structure-activity relationship (3D-QSAR) on 27 novel diacylurea derivatives containing a furan moiety. For the CoMFA study, variation of grid spacing was used during the optimization of the CoMFA model. For the CoMSIA study, the influence of the combination of different field types was evaluated and the best combination was considered to be of steric and H-bonding donor fields. Variation of the grid spacing and attenuation factor was studied to get the best CoMSIA model. A reasonable model with strong predictive ability was obtained from the investigation of CoMFA and CoMSIA models, which had non-cross validated coefficient r2 of 0.828 and 0.841 respectively. The 3D contour maps by the CoMFA and CoMSIA provided smooth and interpretable explanation of the structure-insecticidal activity relationship for the compounds. The analysis of the 3D contour maps will lead to insight into the further structural optimization.