Design, Synthesis, Insecticidal Activities, and Structure–Activity Relationship of Phenylpyrazole Derivatives Incorporating 1,2,4-Oxadiazole Moiety

The ryanodine receptors (RyRs) represent an optimal target for insecticide development. To explore novel structures of RyRs agonists, a series of compounds containing 1,2,4-oxadiazole were designed and synthesized based on the RyRs structure. The compounds were confirmed by 1H and 13C nuclear magnetic resonance as well as high-resolution mass spectrometry. Additionally, bioassays demonstrated that the majority of the newly synthesized compounds exhibited complete mortality (100%) against Plutella xylostella and Mythimna separata at a concentration of 50 mg/L. Furthermore, compound II5 showed a slightly higher LC50 value (LC50 = 0.20 mg/L) compared to the control chlorantraniliprole (LC50 = 0.06 mg/L) against M. separata. Through the toxicity study of the target compounds on Spodoptera frugiperda carrying the resistant mutant RyR (I4790M), it was confirmed that these target compounds have a similar mode of action to chlorantraniliprole. Moreover, the binding modes of these compounds were investigated, revealing that 1,2,4-oxadiazole serves as an effective substitute structure for amide bonds. These findings provide valuable insights for further structural optimization.