文献类型：期刊文献

英文题名：Design, Synthesis, and Insecticidal Activity of 3-(6-Methyltriazinone)-3,4-dihydrobenzo[b][1,5]diazin-2(1H)-ones: Conformationally Restricted Pymetrozine Analogues

作者：Li, Xiaoyang[1];Zhou, Cong[1];Yang, Wulin[1];Li, Zhong[1];Cheng, Jiagao[1]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China

年份：2024

卷号：9

期号：42

外文期刊名：CHEMISTRYSELECT

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001368142500001)】；

基金：The authors gratefully acknowledge the financial support from the National Key Research and Development Program of China (2023YFD1700501), Natural Science Foundation of Shanghai (22ZR1415600), National Natural Science Foundation of China (22307039), China Postdoctoral Science Foundation (2023M731089), and Postdoctoral Fellowship Program of CPSF (GZC20230806).

语种：英文

外文关键词：Conformational restriction; Molecular docking; Pymetrozine; Ring-closure; TRPV channel

摘要：A series of novel 3-(6-methyltriazinone)-3,4-dihydrobenzo[b][1,5]diazin-2(1H)-one derivatives was designed and synthesized as conformationally restricted analogues of insecticide pymetrozine. Conformational and physicochemical properties analyses indicated the rationality in reducing the energy barrier between the lowest-energy and predicted bioactive conformations, as well as pesticide-likeness. Insecticidal bioassays showed that the optimal compound VI-6b exhibited a mortality rate of 67.7% against Aphis craccivora at 400 mg L-1. The molecular docking study of VI-6b within the Nilaparvata lugens TRPV channel elucidated the predicted binding mode, wherein VI-6b forms hydrogen bonds with Arg646 and Glu727, while engaging in pi-pi interactions with Phe688. However, physicochemical properties revealed that low lipophilicity and poor aqueous solubility limited the insecticidal efficacy of these novel compounds. This study provides valuable insights for the future design of insecticides targeting the TRPV channel.