Mode anthranilic diamides

To assess activity at the insect ryanodine receptor, pyridyl pyrazoles of Table II were tested in a calcium mobilization assay, using neurons from the American cockroach, Periplaneta americana. These studies have confirmed the mode of action to be RyR activation. Compounds D11-D17 showed exceptional potency in this assay with activity in the range of0.03-0.30 pM. The data shows the ability of anthranilic diamides to release internal calcium stores while failing to activate voltage-gated calcium channels. Furthermore, calcium mobilization induced by anthranilic diamides is blocked following treatment with 1 pM ryanodine, consistent with action at the ryanodine receptor. 

The discovery of a novel class of anthranilic diamide insecticides having exceptional activity against a broad spectrum of Lepidoptera at extremely low rates of application has successfully led to the commercialization of Rynaxypyr (2). Compounds of this chemistry class exert their effect by causing release of intracellular Ca stores in muscle cells by activation of the ryanodine receptor. As a new mode-of-action product with outstanding insecticidal properties, Rynaxypyr offers great promise for the marketplace. 

The mode of action of anthranilic diamides has been investigated in detail. It was reported that anthranilic diamides activate RyR, releasing stored calcium from the sarcoendoplasmic reticulum, and exhibit >500-fold differential selectivity toward insect, over mammalian, receptors [32). Anthranilic diamides will be soon classified as RyR modulators within the I RAC classification [2). The two chemical classes, benzenedicarboxamides and anthranilic diamides, could contribute to our understanding of the mechanism of calcium release channels in insects and mammals. 

Benzenedicarboxamide compounds, including flubendiamide, were found through original research at NNC. However, notably, anthranilic diamides, structurally very different from benzenedicarboxamides, were discovered by DuPont [20] to have the same mode of action [21] and a couple of companies are following with patent applications Nissan Chemical [41] and Takeda Pharmaceutical Company [42] have applied for patents of the related compounds of benzenedicarboxamides, and Ishihara Sangyo Kaisha [43] has applied for patent of the related compounds of anthranilic diamides. The market entry of insecticides from this new generation could intensify competition with conventional insecticides in the future. 

The Novel Mode of Action of Anthranilic Diamide Insecticides Ryanodine Receptor Activation... 

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