Discovery and optimization of a novel insecticide, broflanilide

Nakao, Toshifumi; Katsuta, Hiroyuki; Nomura, Michikazu; Wakita, Takeo; Daido, Hidenori; Kobayashi, Yumi; Kawahara, Atsuko; Banba, Shinichi

doi:10.1016/b978-0-12-821035-2.00006-1

Cited by 6 publications

(13 citation statements)

References 17 publications

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“…4). 119,120 The meta‐diamides were not only highly insecticidal, but also again resulted in a change in the MoA. Interestingly, the MoA of broflanilide turns out to be the same as that of the isoxazolines, i.e.…”

Section: Approaches To the Discovery Of Fic Insecticides: Selected Ex...mentioning

confidence: 99%

“…Interestingly, the MoA of broflanilide turns out to be the same as that of the isoxazolines, i.e. GABA‐gated chloride channel allosteric modulators 25,120 . Thus, from investigations and elaborations of the diamides, two new classes (meta‐diamides and isoxazolines) of insecticides have emerged, both sharing a common new MoA.…”

Section: Approaches To the Discovery Of Fic Insecticides: Selected Ex...mentioning

confidence: 99%

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Innovation in insecticide discovery: Approaches to the discovery of new classes of insecticides

Sparks¹,

Bryant

2022

Pest Management Science

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The continuing demand for agrochemical insecticides that can meet increasing grower, environmental, consumer and regulatory requirements creates the need for the development of new solutions for managing crop pest insects. The development of resistance to the currently available insecticidal products adds another critical driver for new insecticidal active ingredients (AIs). One avenue to meeting these challenges is the creation of new classes of insecticidal molecules to act as starting points and prototypes stimulating further spectrum, efficacy and environmental impact refinements. A new class of insecticides is foreshadowed by the first molecule exemplifying that class (first‐in‐class, FIC) and offers one measure of innovation within the agrochemical industry. Most insecticides owe their discovery to competitor‐inspired (i.e. competitor patents/products) or next‐generation (follow‐on to a company's pre‐existing product) strategies. In contrast, FIC insecticides primarily emerge from a bioactive hypothesis approach, with the largest segment resulting from the exploration of new areas of chemistry/heterocycles and underexploited motifs. Natural products also play an important role in the discovery of FIC insecticides. Understanding the origins of these FIC compounds and the approaches used in their discovery can provide insights into successful strategies for future FIC insecticides. This review analyses information on historic and recently introduced FIC insecticides. Its main objective has been to identify the most successful discovery strategies for identifying new agrochemical solutions to meet the challenge of minimizing crop losses resulting from insects. © 2022 Society of Chemical Industry.

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Section: Approaches To the Discovery Of Fic Insecticides: Selected Ex...mentioning

confidence: 99%

Section: Approaches To the Discovery Of Fic Insecticides: Selected Ex...mentioning

confidence: 99%

Innovation in insecticide discovery: Approaches to the discovery of new classes of insecticides

Sparks¹,

Bryant

2022

Pest Management Science

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“…Further successful examples of amide reversal have been reported in the classes of scytalone dehydratase, cellulose synthase, , oxysterol binding protein , and histone deacetylase , inhibiting fungicides, as well as for Complex I inhibiting and GABA-gated chloride channel modulating insecticides …”

Section: Reversal Of the Carboxamide Functionmentioning

confidence: 99%

Reversal of Functional Groups as a Useful Scaffold Hopping Tool in Agrochemistry

Lamberth

2022

J. Agric. Food Chem.

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Reverting the orientation of a functional group by exchanging molecular parts of it is an important scaffold hopping manipulation, as biologically active compounds and their analogs, which underwent such a transformation, are often similar in shape and physicochemical properties and therefore likely in their potency as well. This review will demonstrate, how the inversion of carboxamides, sulfonamides, carbamates, oximes, hydrazones, O,S-acetals, and ethers led to the discovery of highly active agrochemicals.

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“…In fact, no cross-resistance between meta-diamides and NCAs was observed. 12) The resistant strains, which carry the A2′ mutations in the GABA receptor, were resistant to dieldrin and fipronil.…”

Section: Interaction Of Meta-diamides With Gaba Receptorsmentioning

confidence: 99%

“…In contrast, both meta-diamide 7 and broflanilide were effective against the resistant strains. 12) Based on these findings, broflanilide was classified into a new IRAC group 30, GABA-gated chloride channel allosteric modulators.…”

Section: Interaction Of Meta-diamides With Gaba Receptorsmentioning

confidence: 99%

Application of computational methods in the analysis of pesticide target-site and resistance mechanisms

Banba

2021

J. Pestic. Sci.

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Meta-diamide insecticides including broflanilide have a high insecticidal activity by acting on RDL GABA receptors. Both membrane potential assays and docking studies suggest that the target site of meta-diamides is different from that of conventional noncompetitive inhibitors, such as fipronil. In fact, meta-diamides are effective against cyclodiene-and fipronil-resistant pests that carry target-site mutations. Dinotefuran uniquely possesses a tetrahydrofuran ring, whereas other neonicotinoids possess aromatic rings. Moreover, dinotefuran has been reported to be effective against imidacloprid-resistant strains. A docking study predicted the weak binding of dinotefuran to cytochrome P450s which are associated with imidacloprid resistance. Metabolic assays revealed that dinotefuran was not metabolized by these cytochrome P450s. These findings suggest that the lack of metabolic activity of P450s against dinotefuran causes a low level of cross-resistance.

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Discovery and optimization of a novel insecticide, broflanilide

Cited by 6 publications

References 17 publications

Innovation in insecticide discovery: Approaches to the discovery of new classes of insecticides

Innovation in insecticide discovery: Approaches to the discovery of new classes of insecticides

Reversal of Functional Groups as a Useful Scaffold Hopping Tool in Agrochemistry

Application of computational methods in the analysis of pesticide target-site and resistance mechanisms

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