Design, Synthesis, and Insecticidal Activity of Novel Chiral Isoxazoline Thiourea Derivatives

The application of chiral pesticides in agriculture is becoming more important. To investigate pest control methods that focus on the γ-aminobutyric acid receptor (GABAR), we designed and synthesized a new chiral isoxazoline thiourea inhibitor and thoroughly assessed its insecticidal properties, along with the structure–activity relationships. Bioassay findings showed that compound S-19 demonstrated outstanding insecticidal effectiveness, with LC50 values of 0.24, 0.94, and 0.89 mg/L against Plutella xylostella, Spodoptera frugiperda, and Spodoptera exigua, respectively, which were similar to fluralaner (LC50 = 0.20, 0.86, and 0.84 mg/L). Molecular modeling results suggested that S-19 could establish more advantageous ΔEvdw and ΔEele interactions with P. xylostella GABAR, resulting in a more favorable ΔGbind. Compound S-19, identified as a highly promising insecticidal candidate targeting the GABAR, offers a valuable lead compound for the further design and synthesis of new isoxazole insecticides.