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

Abstract A series of novel 3‐(6‐methyltriazinone)‐3,4‐dihydrobenzo[ b ][1,5]diazin‐2(1 H )‐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 π‐π 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.