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 (LC50) values of compounds X-30 and X-40 against Mythimna separata were 0.09 and 0.08 mg L-1, respectively, which are lower than that of chlorantraniliprole (CHL, 0.11 mg L-1). Notably, compounds X-10, X-18, X-25, X-32 and X-43 had corresponding LC50 values of 2.0 × 10-4, 5.0 × 10-4, 6.0 × 10-4, 9.0 × 10-4 and 7.0 × 10-4 mg L-1 against Plutella xylostella, respectively. The best compound X-10 exhibited five-fold greater efficacy than CHL (1.0 × 10-3 mg L-1). The LC50 values of compounds X-21, X-29, and X-40 against Spodoptera frugiperda were 0.27, 0.26 and 0.25 mg L-1, respectively, which are slightly lower than that of CHL (0.33 mg L-1). In the case of Ostrinia furnacalis, compound X-43 showed good efficacy with LC50 values comparable to those of CHL (1.38 versus 1.57 mg L-1). 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.