Design, Synthesis, Insecticidal Activity, and SAR of Aryl Isoxazoline Derivatives Containing Pyrazole-5-carboxamide Motif.

It is important to develop new insecticides with a new mode of action because of increasing pesticide resistance. In this study, a series of novel aryl isoxazoline derivatives containing the pyrazole-5-carboxamide motif were designed and synthesized. Their structures were confirmed by H NMR, C NMR, and HRMS. Bioassays indicated that the 24 compounds synthesized possessed excellent insecticidal activity against and no activity against and . Among these aryl isoxazoline derivatives, 3-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydrozol-3-yl)--(4-fluorophenyl)-1-methyl-1-pyrazole-5-carboxamide () had the best insecticidal activity against , which is comparable with the positive control fluralaner. The molecular docking results of compound and fluralaner with the GABA model demonstrated the same docking mode between compound and positive control fluralaner in the active site of GABA. Molecular structure comparisons and ADMET analysis can potentially be used to design more active compounds. The structure-activity relationships are also discussed. This work provided an excellent insecticide for further optimization.