Synthesis, Insecticidal Activities, and 3D-QASR of <i>N</i>‑Pyridylpyrazole Amide Derivatives Containing a Phthalimide as Potential Ryanodine Receptor Activators

To develop potent and environment-friendly insecticides, novel N-pyridylpyrazole amide derivatives containing a phthalimide were designed and synthesized. The preliminary bioassay results showed that most of the target compounds exhibited good insecticidal activities. For oriental armyworm (Mythimna separata), compounds E5, E29, E30, and E33 displayed higher than 90% lethal rates at 25 mg L–1. In particular, compound E33 displayed 60% mortality at a lower concentration of 6.25 mg L–1. Besides, compound E33 also showed a 30% lethal rate at 5 mg L–1 against diamondback moth (DBM) (Plutella xylostella). Molecular docking between the most active compound E33 and DBM ryanodine receptor (RyR), comparative molecular field analysis (CoMFA), and density functional theory (DFT) calculations were conducted and discussed. Furthermore, according to vitro studies using a calcium imaging technique, compound E33 was a potent novel lead targeting insect RyR