Anthranilic Diamides Containing Monofluoroalkene Amide Linkers as Potential Insect RyR Activators: Design, Synthesis, Bio-evaluation, and Computational Study.

In order to develop anthranilic diamides with novel chemotypes, a series of anthranilic diamides with acrylamide linkers were designed and synthesized. The results of preliminary bioassays indicated that compounds with a monofluoroalkene amide linker (-isomer) exhibited good larvicidal activity against lepidopteran pests. The LC values of compound against and were 1.44 and 3.48 mg·L, respectively, while those of chlorantraniliprole were 0.08 and 0.06 mg·L, respectively. Compound also exhibited the same level of lethal potency against resistant and susceptible strains of at 50 mg·L. Compound exhibited similar symptoms as chlorantraniliprole in test larvae. Comparative molecular field analysis was conducted to demonstrate the structure-activity relationship. Central neuron calcium imaging experiments indicated that monofluoroalkene compounds were potential ryanodine receptor (RyR) activators and activated calcium channels in both the endoplasmic reticulum and the cell membrane. Molecular docking suggested that had a better binding potency to RyR than chlorantraniliprole. The MM|GBSA dG bind value of with RyR was 117.611 kcal·mol. Monofluoroalkene was introduced into anthranilic diamide insecticides for the first time and brought a novel chemotype for insect RyR activators. The feasibility of fluoroalkenes as insecticide fragments was explored.