Computer-aided design of novel anthranilic diamides containing fluorinated alkoxy groups as potential ryanodine receptor insecticides.

Background: Increasing the diversity of lead compounds has been shown to enhance the efficacy of diamide insecticides. Fifty novel compounds were precisely designed and synthesized utilizing fragment-based assembly and virtual screening coupling.

Results: The median lethal concentration (LC) values of compounds X-30 and X-40 against Mythimna separata were 0.09 and 0.08 mg L, respectively, which are lower than that of chlorantraniliprole (CHL, 0.11 mg L). Notably, compounds X-10, X-18, X-25, X-32 and X-43 had corresponding LC values of 2.0 × 10, 5.0 × 10, 6.0 × 10, 9.0 × 10 and 7.0 × 10 mg L against Plutella xylostella, respectively. The best compound X-10 exhibited five-fold greater efficacy than CHL (1.0 × 10 mg L). The LC values of compounds X-21, X-29, and X-40 against Spodoptera frugiperda were 0.27, 0.26 and 0.25 mg L, respectively, which are slightly lower than that of CHL (0.33 mg L). In the case of Ostrinia furnacalis, compound X-43 showed good efficacy with LC values comparable to those of CHL (1.38 versus 1.57 mg L). Calcium imaging experiments demonstrated that X-21 acted on S. frugiperda ryanodine receptors. Furthermore, this series of compounds showed safety toward nontarget mammals compared to CHL.

Conclusion: The introduction of fluorinated alkoxy groups at the 3-position of the pyrazole ring leads to good insecticidal activity and improved insect selectivity. © 2025 Society of Chemical Industry.