文献类型：期刊文献

英文题名：Bioisosteric-Replacement-Driven Lead Optimization of Tyclopyrazoflor

作者：Chen, Meijun[1];Li, Zhong[1,2];Shao, Xusheng[1,2,3,4];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, Shanghai Frontier Sci Res Base Optogenet Tech Cel, 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 Rodersdatf, Switzerland

年份：2022

卷号：70

期号：36

起止页码：11123

外文期刊名：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

收录：;EI(收录号：20222212183906);WOS:【SCI-EXPANDED(收录号:WOS:000821475500001)】；

语种：英文

外文关键词：tyclopyrazoflor; bioisosteric replacement; SwissBioisostere; pyridazine; density functional theory (DFT)

摘要：A heterocyclic replacement strategy has been applied attempting to further optimize the biological properties of the new insecticide tyclopyrazoflor, a pyridinyl-pyrazole compound with excellent activity against sap-feeding insects recently discovered by Corteva. Our research program on this novel chemical class of insecticide was targeted to evaluate the importance of both the pyridyl and pyrazole moieties on the biological activity, properties, and structure-activity. Synthetic methodologies have been developed delivering our designed target compounds in moderate to good yields. In our attempt to rationalize the biological activity differences of tyclopyrazoflor analogues, a potential surface analysis based on a density functional theory (DFT) calculation and DFT-derived Multiwfn and VMD program model was performed. Furthermore, the SwissBioisostere online database was applied as a great source for inspiration for bioisosteric replacements.