文献类型：期刊文献

英文题名：Scaffold-Hopping Approach To Identify New Chemotypes of Dimpropyridaz

作者：Chen, Meijun[1];Li, Zhong[1,2];Shao, Xusheng[1,3,4];Maienfisch, Peter[1,5]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai Frontier Sci Res Base Optogenet Tech Cell, Shanghai 200237, Peoples R China;[4]East China Univ Sci & Technol, Engn Res Ctr Pharmaceut Proc Chem, Sch Pharm, Minist Educ, Shanghai 200237, Peoples R China;[5]CreInSol Consulting & Biocontrols, CH-4118 Rodersdorf, Switzerland

年份：2022

卷号：70

期号：36

起止页码：11109

外文期刊名：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

收录：;EI(收录号：20221712025409);WOS:【SCI-EXPANDED(收录号:WOS:000823587500001)】；

基金：Funding This work was financially supported by the National Natural Science Foundation of China (21877039 and 32072441) , the Innovation Program of Shanghai Municipal Education Commission (2017-01-07-00-02-E00037) , and the Shangha i Frontiers Science Center of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission) .

语种：英文

外文关键词：dimpropyridaz; pyrazole carboxamide insecticide; scaffold hopping; heterocyclic replacement; 1, 2-diazine; density functional theory (DFT)

摘要：Dimpropyridaz is a pyrazole carboxamide insecticide with a novel mode of action, currently under worldwide development by BASF, providing excellent activity against sucking pests. A series of dimpropyridaz analogues were designed to investigate the impact of bioisosteric heterocyclic replacements on the biological activity and molecular properties. Focus was given to prepare analogues where the 4-pyridazinyl moiety was replaced by 5-pyrimidinyl, 2-pyrimidinyl, 3-pyridazinyl, and 2-pyrazinyl groups. Five different synthetic routes were developed for the preparation of these analogues, delivering the target compounds in moderate to good yields. We explained some aspects of the observed structure-activity relationship by a density functional theory (DFT) calculation and DFT-derived Multiwfn and VMD program models. These findings provide first insights into the important role of the 4-pyridazinyl heterocyclic moiety in the pyrazole carboxamide insecticide chemical class and the mechanism of action of dimpropyridaz.