Novel Fluorinated Aniline Anthranilic Diamides Improved Insecticidal Activity Targeting the Ryanodine Receptor.

The diamide insecticides show exceptional activity against insects via activation of ryanodine receptors (RyRs). In the present study, a series of anthranilic diamides containing a fluoroaniline moiety were designed, synthesized, and evaluated for insecticidal potency. Most titled compounds exerted moderate to remarkably high activity against , , and . The insecticidal activity of compound and against was 26.7 and 26.7% at 0.1 mg L, respectively, equivalent to that of chlorantraniliprole (0.1 mg L, 30.0%). Compounds , , and exhibited 8.0-, 1.8-, and 4.7-fold higher potency than chlorantraniliprole against , respectively, as compared with their LCs. Compounds and showed good insecticidal activity against with LC of 0.56 and 0.46 mg L, respectively, comparable to that of the commercial insecticide chlorantraniliprole with LC of 0.31 mg L. Calcium imaging experiments indicated RyRs as the action target. Molecular docking suggested a higher binding energy of 8.647 kcal/mol between and the RyR than the 7.820 kcal/mol between chlorantraniliprole and the RyR. Meanwhile, the docking results of with mutated RyR at site G4946E showed that could have a good inhibition effect on the resistant . The density functional theory calculations suggested the importance of the fluoroaniline moiety in potency. Those novel anthranilic diamides containing a fluorinated aniline moiety are good insecticidal candidates.