Design, Synthesis, and Structure–Activity Relationship of Novel Quinazolinone Derivatives

A series of novel quinazolinone derivatives targeting Aphis fabae were designed and synthesized. Their structures were confirmed through comprehensive analyses of 1H and 13C NMR and MS data. Biological assays showed that compounds 9-4, 9-7, 9-8, and 10-7 exhibit superior insecticidal activity against A. fabae compared to commercial compounds pyrifluquinazon, imidacloprid, and pymetrozine. Field trials further validated 10-7’s long-lasting efficacy and enhanced control of imidacloprid-resistant aphid populations. Acute toxicity assays indicated that compound 10-7 had a low mammalian toxicity. A structure–activity relationship (SAR) identified key functional groups critical for bioactivity, while molecular docking simulations elucidated the mechanism of action, revealing hydrogen-bond interactions with ASN 572 of the TRPV channel. These findings establish 10-7 as a promising lead candidate for developing sustainable insecticides with resistance-breaking potential, advancing both agrochemical innovation and integrated pest management strategies.