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 <i>S</i>-<b>19</b> demonstrated outstanding insecticidal effectiveness, with LC₅₀ values of 0.24, 0.94, and 0.89 mg/L against <i>Plutella xylostella</i>, <i>Spodoptera frugiperda</i>, and <i>Spodoptera exigua</i>, respectively, which were similar to fluralaner (LC₅₀ = 0.20, 0.86, and 0.84 mg/L). Molecular modeling results suggested that <i>S</i>-<b>19</b> could establish more advantageous Δ<i>E</i>_vdw and Δ<i>E</i>_ele interactions with <i>P. xylostella</i> GABAR, resulting in a more favorable Δ<i>G</i>_bind. Compound <i>S</i>-<b>19</b>, 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.