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

Abstract

To develop potent and environment-friendly insecticides, novel <i>N</i>-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 (<i>Mythimna separata</i>), compounds <b>E</b>_<b>5</b>, <b>E</b>_<b>29</b>, <b>E</b>_<b>30</b>, and <b>E</b>_<b>33</b> displayed higher than 90% lethal rates at 25 mg L^-1. In particular, compound <b>E</b>_<b>33</b> displayed 60% mortality at a lower concentration of 6.25 mg L^-1. Besides, compound <b>E</b>_<b>33</b> also showed a 30% lethal rate at 5 mg L^-1 against diamondback moth (DBM) (<i>Plutella xylostella</i>). Molecular docking between the most active compound <b>E</b>_<b>33</b> 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 <b>E</b>_<b>33</b> was a potent novel lead targeting insect RyR.