Novel Anthranilic Diamide Scaffolds Containing N-Substituted Phenylpyrazole as Potential Ryanodine Receptor Activators

Abstract

To discover potent insecticides targeting ryanodine receptors (RyRs), a series of novel anthranilic diamides analogues (12a-12u) containing N-substituted phenylpyrazole were designed and synthesized. These compounds were characterized by (1)H NMR, (13)C NMR, and HRMS, and the structure of compound 12u was confirmed by X-ray diffraction. Their insecticidal activities indicated that these compounds displayed moderate to excellent activities. In particular, 12i showed 100 and 37% larvicidal activities against oriental armyworm (Mythimna separata) at 0.25 and 0.05 mg L(-1), equivalent to that of chlorantraniliprole (100%, 0.25 mg L(-1); and 33%, 0.05 mg L(-1)). The activity of 12i against diamondback moth (Plutella xylostella) was 95% at 0.05 mg L(-1), whereas the control was 100% at 0.05 mg L(-1). The calcium-imaging technique experiment results showed that the effects of 12i on the intracellular calcium ion concentration ([Ca(2+)]i) in neurons were concentration-dependent. After the central neurons of Helicoverpa armigera were dyed by loading with fluo-5N and treated with 12i, the free calcium released in endoplasmic reticulum indicated the target of compound 12i is RyRs or IP3Rs. The activation of RyRs by natural ryanodine completely blocked the calcium release induced by 12i, which indicated that RyRs in the central neurons of H. armigera third-instar larvae is the possible target of compound 12i.

Synthesis, insecticidal evaluation and 3D‐QSAR study of novel anthranilic diamide derivatives as potential ryanodine receptor modulators

“…Insecticidal activity against M. separata varied remarkably depending upon substituents (R ′ 3 and R ′ 4 ) on the benzene ring of the phenylpyrazole moiety. In general, when R 1 , R 2 , and R ′ 3 were fixed, the overall sequence of R ′ 4 related to the larvicidal activity of title compounds was Cl > CF 3 > H ≥ CH 3 The results indicated that all tested target compounds exhibited excellent insecticidal activity at the concentration of 5 mg L −1 . Moreover, it was noteworthy that some compounds, such as 6a, 6h, 6p, and 6r, had potent activity when compared with the standard chlorantraniliprole.…”

“…Different substituted phenylhydrazines 1a–1c and compounds 4a–4f were prepared as described in the literature with some modifications as shown in Fig. .…”

“…Insecticides play an essential role in integrated pest management by protecting crops from plant diseases and insects in modern agriculture . However, environmental concerns and resistance development to older insecticides have become serious issues for pest management . Environmentally friendly insecticides with novel modes of action are needed urgently.…”

“…1,2 However, environmental concerns and resistance development to older insecticides have become serious issues for pest management. 3,4 Environmentally friendly insecticides with novel modes of action are needed urgently. Anthranilic diamide insecticides that have been classified as a new group (28: ryanodine receptor modulators) satisfy the demands exactly.…”

Chemical synthesis, crystal structure, versatile evaluation of their biological activities and molecular simulations of novel pyrithiobac derivatives

“…The insecticidal activity of title compounds and rynaxypyr against oriental armyworm (Mythimna separata) was tested according to the leaf-dip method using the reported procedure at 600 mg/L dose [32].…”