Design, Synthesis, and Insecticidal Activities of Novel N-Alkoxyalkyl Meta-Diamides as Potential GABAR Antagonists

N-alkyl meta-diamides (Ia-If) and N-alkoxyalkyl meta-diamides (IIa-IIIe) were designed and synthesized by using the intermediate derivatization method. Their insecticidal activities were systematically evaluated against resistant Plutella xylostella. Interestingly, the insecticidal activity of compounds IIa-IIIe against resistant P. xylostella showed remarkable consistency with that against sensitive strains of P. xylostella, Spodoptera frugiperda, and Chilo suppressalis. Rapid bioassay results on sensitive P. xylostella revealed outstanding efficacy, particularly for compound IId, which demonstrated mortality rates of 60% and 100% at a concentration of 0.1 μg·mL^-1 after 12 and 24 h of exposure, respectively, significantly outperforming broflanilide. To investigate the molecular mechanism of compound IId, comparative bioactivity assays using both wild-type (w¹¹¹⁸) and mutant (Rdl^G335M) Drosophila were conducted, conclusively demonstrating that Rdl^G335 serves as a critical binding site for compound IId. These findings provide significant insights for the strategic design of meta-diamide compounds, offering a promising approach for managing resistant pest populations.