Design, synthesis and biological activity of diamide compounds based on 3‐substituent of the pyrazole ring^†

Abstract

BACKGROUND Diamide insecticides have attracted significant attention due to their high efficacy and low toxicity to non‐target organisms since they were introduced to the market. In order to tackle the problems of insecticide resistance and ecological safety, 16 novel nitrobenzene substituted anthranilic diamides with ester, hydroxyl or sulfonyl at the 3‐position of the pyrazole ring were designed and synthesized. RESULTS All of these compounds possessed good activity against the ryanodine receptor (RyR) from Spodoptera frugiperda and relatively lower activity against mammalian RyR1, showing a better insect‐selectivity compared to chlorantraniliprole in a cell‐based assay. The molecular docking analysis predicted the binding conformations of these compounds, which showed a good correlation between the insecticidal activity and the binding scores. In vitro studies using a calcium imaging method demonstrated that the novel compounds could not only activate the RyR but may also target the dihydropyridine receptor on the plasma membrane of insect neurons, implicating a similar but not same mode of action. CONCLUSION Substituted anthranilic diamides with an ester at the 3‐position of the pyrazole ring exhibited a promising insecticidal activity and better insect‐selectivity, which provided insight into the rational design of a new generation of effective diamide insecticides.

Anthranilic Diamides Containing Monofluoroalkene Amide Linkers as Potential Insect RyR Activators: Design, Synthesis, Bio-evaluation, and Computational Study

“…Partial least-squares (PLS) analysis was used to establish statistical parameters including q 2 (cross-validated correlation), r 2 (optimum number of components), ONCs (non-crossvalidated correlation), SEE (standard error of estimate), and F-value to evaluate the statistical significance and predictive ability of the CoMFA model. 46,47 ■ RESULTS AND DISCUSSION Synthesis. The synthetic methods of key intermediates 2, 3, 9, 10, 4a−4l, and 5a−5k are shown in Scheme 1.…”

Structural design and insecticidal activity of 1,3,4‐oxadiazole‐ring containing pyridylpyrazole‐4‐carboxamides

“…The diamide molecular structure can be transformed to a 1,3,4-oxadiazole by the annulation of benzylmethylamine. In contrast, it has been shown that maintaining the structures of pyridine, pyrazole, oxazole, triazole, thiazole, and pyridylpyrazolyl at the other amide side could enhance insecticidal activity [21], and modifying the pyrazole ring proved to have a minor effect on its activity [30], and even increasing it [31][32][33][34]. Thus, altering the pyrazole structure while maintaining high activity, such as by changing the bridging position of the pyrazole ring is reasonable, and investigating the influence of such modifications could be interesting.…”

Novel Fluorinated Aniline Anthranilic Diamides Improved Insecticidal Activity Targeting the Ryanodine Receptor

“…Therefore, the binding site for anthranilic diamides on the insect RyR may be a promising site for developing selective insecticides targeting insects only. 10,11 The phthalic acid diamide class has yielded flubendiamide, the first synthetic ryanodine receptor insecticide to be commercialized by Bayer. Shortly after the discovery of the phthalic diamide, the anthranilic diamides, including chlorantraniliprole and cyantraniliprole discovered by DuPont, have opened a new era of chemical insecticides.…”

“…The homology of RyRs between insects and mammals is only about 47%, leading to higher selectivity of anthranilic diamide insecticides to insect RyR over mammalian RyRs. Therefore, the binding site for anthranilic diamides on the insect RyR may be a promising site for developing selective insecticides targeting insects only. , The phthalic acid diamide class has yielded flubendiamide, the first synthetic ryanodine receptor insecticide to be commercialized by Bayer. Shortly after the discovery of the phthalic diamide, the anthranilic diamides, including chlorantraniliprole and cyantraniliprole discovered by DuPont, have opened a new era of chemical insecticides. , Chlorantraniliprole has larvicidal activity and partial ovicidal activity against lepidopteran pests.…”