关键词：
苯甲酰基脲类;氨基甲酸酯类;三维定量构效关系;比较分子立场分析法;比较分子相似性指数分析法
摘 要：
为获得活性更佳且同时具备苯甲酰基脲类和氨基甲酸酯类活性的新型双靶标杀虫剂——N-氯磺基-N-甲基氨基甲酸酯衍生物,构建此类化合物的三维定量构效关系(three-dimensional quantitative structure-activity relationship,3D-QSAR)模型,以18种具有双靶标活性的N-氯磺基-N-甲基氨基甲酸酯衍生物为训练集,分别采用比较分子力场分析(comparative molecular field analysis,CoMFA)法和比较分子相似性指数分析(comparative molecular similarity index analysis,CoMSIA)法进行3D-QSAR模型的构建,基于3D-QSAR模型分析同一骨架取代基的变化带给化合物的活性变化,预测不同力场对化合物活性的影响,并对设计的衍生化合物进行活性预测分析。结果表明,经CoMFA法和CoMSIA法构建的3D-QSAR模型可信度高(交叉验证系数q2分别为0.728和0.563),且有良好的活性预测能力(非交叉验证系数r2分别为0.954和0.981)。基于该模型得到的化合物预测活性与实际活性残差较小且存在良好的线性关系,进一步证明所得3D-QSAR模型的可靠性。通过分析3D-QSAR模型的力场分布,推测在R1基团处引入位阻较大的疏水性基团、在R2基团苯环的邻位引入同时具有负电性和疏水性但不含卤素原子的基团、用负电性的大位阻基团取代R基团等均可提高N-氯磺基-N-甲基氨基甲酸酯的活性。基于此设计的20种衍生化合物的活性变化从正反两方面印证了该推测的合理性。研究成果可用于指导兼具苯甲酰基脲类和氨基甲酸酯类杀虫剂作用机制的N-氯磺基-N-甲基氨基甲酸酯衍生物的设计。
译 名：
Construction of two 3D-QSAR models for insecticide-derived compounds targeting acetylcholinesterase and chitin synthase
作 者：
Li Ruichi;Liu Jiyuan;College of Plant Protection, Northwest A&F University;
关键词：
benzoylphenylureas;;carbamate;;3D-QSAR;;CoMFA;;CoMSIA
摘 要：
In order to obtain new dual-target insecticides with better activities of benzoyl urea and carbamate insecticides — N-chlorosulfonyl-N-methyl carbamate derivatives, three-dimensional quantitative structure-activity relationship(3D-QSAR) models of these compounds was constructed. Two 3 D-QSAR models were obtained by training with 18 such derivatives using the comparative molecular field analysis(CoMFA) and the comparative molecular similarity index analysis(CoMSIA) methods. Activity changes caused by different substituents on the same skeleton were analyzed and effects of different force fields on compound activity were predicted using these models. The results showed that the 3 DQSAR models constructed using CoMFA and CoMSIA had the high reliability(q2: 0.728 and 0.563) and the good activity prediction ability(r2: 0.954 and 0.981). The high reliability and predictive ability of the 3 D-QSAR models were further validated by the good linear relationship and low residuals between the predicted activity and the actual activity of the test compounds. Then, based on the force field distributions of the 3 D-QSAR models, it was speculated that introducing hydrophobic groups with greater steric hindrance to R1 or halogen-free groups characterized by electronegativity and hydrophobicity to the ortho-position of the benzene ring of the R2, or substituting R with negatively charged groups possessing large steric hindrance, could improve the activity of N-chlorosulfonyl-N-methyl carbamate. Rationality of the speculation was confirmed pro and con by the expected activity changes of 20 derivatives designed based on this hypothesis. The results can be used to guide the design of new N-chlorosulfonyl-N-methyl carbamate derivatives with the action mechanisms of benzoyl urea and carbamate insecticides.
