Synthesis, Insecticidal Activities, and 3D-QASR of N -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 E 5 , E 29 , E 30 , and E 33 displayed higher than 90% lethal rates at 25 mg L -1 . In particular, compound E 33 displayed 60% mortality at a lower concentration of 6.25 mg L -1 . Besides, compound E 33 also showed a 30% lethal rate at 5 mg L -1 against diamondback moth (DBM) ( Plutella xylostella ). Molecular docking between the most active compound E 33 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 E 33 was a potent novel lead targeting insect RyR.