Design, Synthesis, and Insecticidal Activity of Mesoionic Pyrido[1,2-<i>a</i>]pyrimidinone Containing Isoxazole/Isoxazoline Moiety as a Potential Insecticide

Abstract

Bean aphid (<i>Aphis craccivora</i>) resistance to commonly used insecticides has made controlling these pests increasingly difficult. In this study, we introduced isoxazole and isoxazoline, which possess insecticidal activity, into pyrido[1,2-<i>a</i>]pyrimidinone through a scaffold hopping strategy. We designed and synthesized a series of novel mesoionic compounds that exhibited a range of insecticidal activities against <i>A. craccivora</i>. The LC₅₀ values of compounds <b>E1</b> and <b>E2</b> were 0.73 and 0.88 μg/mL, respectively, better than triflumezopyrim (LC₅₀ = 2.43 μg/mL). Proteomics and molecular docking analyses showed that <b>E1</b> might influence the <i>A. craccivora</i> nervous system by interacting with neuronal nicotinic acetylcholine receptors (nAChRs). This research offers a new approach to the advancement of novel mesoionic insecticides.