Synthesis, Insecticidal Evaluation, and 3D-QASR of Novel Anthranilic Diamide Derivatives Containing N-Arylpyrrole as Potential Ryanodine Receptor Activators

To cope with the global food shortage and insect pest, there is an urgent need to discover new pesticides with novel modes of actions. Ryanodine receptor (RyR) insecticides showed great promise in integrated pest management. Herein, we report the synthesis of novel anthranilic diamide derivatives incorporating pyrrole moieties targeting at insect RyRs. The structures were confirmed by 1H NMR, 13C NMR, 19F NMR, and high-resolution mass spectrometry. The preliminary bioassay results indicated that most of the title compounds showed good to excellent insecticidal activities against the oriental armyworm (Mythimna separata) and diamondback moth (Plutella xylostella). For the oriental armyworm, Ij displayed the same level of larvicidal activity as the positive control chlorantraniliprole, with an LC50 value of 0.21 mg/L. For the diamondback moth, In, Io, Ip, and Iq exhibited higher insecticidal activities than chlorantraniliprole. In particular, In had 50% larvicidal activity at 0.00001 mg/L. The calcium imaging technique was applied to study the effect of Ij, In, and Ip on the intracellular calcium ion concentration ([Ca2+]i) in central neurons isolated from the oriental armyworm. The results indicated that the tested compounds, such as chlorantraniliprole, could activate the insect RyRs. Furthermore, comparative molecular field analysis and density functional theory calculations were carried out to study the structure–activity relationship.