Design, synthesis, and insecticidal evaluation of novel anthranilic diamides of N-pyridylpyrazole derivatives containing 3-thioethers

Thioether and its derivatives are important active pharmacophores, widely adopted in the molecular design of agrochemicals. The introduction of thioether into drug intermediate is important to improve the liposolubility, hydrophobicity, and bioactivity of molecules. For development of novel insecticides targeting at ryanodine receptor (RyR), a series of anthranilic diamides of N-pyridylpyrazole derivatives containing 3-thioether were designed and synthesized. The structures of these compounds were verified using H-1 NMR, C-13 NMR, and HRMS. Their insecticidal activities against Mythimna separata (M. separata, oriental armyworms) and Plutella xylostella (P. xylostella, diamondback moths) were evaluated and the preliminary structure-activity relationship (SAR) was discussed, among which 9f, 9g exhibited favorable insecticidal activities against M. separata at 5 mg/L (9f, 50%; 9g, 40%). In addition, insecticidal activity of the intermediate 8 indicated that bromomethyl group at 3-position of pyrazole moiety has an important impact for retaining insecticidal activity. Calcium imaging experiment and molecular docking were carried out to elaborate insecticidal mechanism from the perspective of experiment and molecular simulation, respectively.