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 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.