Discovery of diamide derivatives bearing a flexible substituted benzylamine moiety as potential ryanodine receptor activator.

BACKGROUND

Lepidopteran pests have developed severe resistance to diamide insecticides, posing a huge challenge to effective pest control, necessitating the development of novel insecticides to achieve the effective comprehensive management of pests. Forty-two novel derivatives bearing substituted benzylamine moieties with chlorantraniliprole (CHL) as the lead compound were precisely design, synthesized, and evaluated for insecticidal activities against three Lepidopteran pests.

RESULTS

The bioassay results showed that the LC50 values of compounds A26 and A40 against Mythimna separata were 0.080 and 0.163 mg L-1, respectively, comparable to that of CHL (LC50 0.124 mg L-1). For Plutella xylostella, the LC50 values of A16 and A40 were 0.041 and 0.048 mg L-1, respectively, equivalent to that of CHL (LC50 0.049 mg L-1). Additionally, compound A40 showed insecticidal activity against Spodoptera frugiperda comparable to that of CHL (LC5 0.279 vs 0.174 mg L-1) and exhibited significantly superior efficacy against the resistant strain (LC50 75.83 vs 141.75 mg L-1). These results indicate that A40 exhibits excellent insecticidal efficacy against Lepidopteran pests. Calcium imaging experiments suggested that compound A40 targets the insect ryanodine receptors, which was further validated by transcriptome analysis and molecular docking assays.

CONCLUSIONS

This research will provide valuable insights for the development of novel diamide insecticides containing benzylamine scaffolds. © 2026 Society of Chemical Industry.