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-1 NMR, C-13 NMR, and HRMS. Bioassays indicated that the 24 compounds synthesized possessed excellent insecticidal activity against Mythimna separate and no activity against Aphis craccivora and Tetranychus cinnabarinus. Among these aryl isoxazoline derivatives, 3-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydrozol-3-yl)-N-(4-fluorophenyl)-1-methyl-1H-pyrazole-5-carboxamide (IA-8) had the best insecticidal activity against M. separate, which is comparable with the positive control fluralaner. The molecular docking results of compound IA-8 and fluralaner with the GABA model demonstrated the same docking mode between compound IA-8 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.

Automated summary

This study focused on the design and synthesis of a series of novel insecticides. One compound, IA-8, showed excellent insecticidal activity against M. separate, comparable to the positive control fluralaner. Molecular docking results demonstrated that IA-8 and fluralaner have a similar binding mode to the GABA active site. This work provides a promising starting point for further optimization of insecticides.