Design, Synthesis, and Insecticidal Evaluation of N-Pyridylpyrazole Amide Derivatives Containing 4,5-Dihydroisoxazole Amide as Potential Ryanodine Receptor Activators

Using the 4,5-dihydroisoxazol amide structure to expand the aliphatic amide moiety of chlorantraniliprole, a series of 28 novel N-pyridylpyrazolecarboxamide derivatives containing 4,5-dihydroisoxazol amide fragment were designed and synthesized. All target compounds had been properly characterized and confirmed by 1H NMR, 13C NMR, and HRMS, and the effects were evaluated against Mythimna separata(M. separata) and Plutella xylostella(P. xylostella). The bioassay results indicated that most of the target compounds exhibited good insecticidal activities against M. separataand P. xylostellaat 50 mg/L; especially, compound A4showed an LC50value of 3.27 mg/L against M. separata. Calcium imaging experiments indicated that the target compound A4had a similar mechanism of action to chlorantraniliprole, causing an increase in the cytoplasmic Ca2+concentration. The molecular docking revealed the possible binding mode of compound A4with a ryanodine receptor.