title: Flupyradifurone (Sivanto™) and its novel butenolide pharmacophore: Structural considerations.
abstract: Flupyradifurone (4-[(2,2-difluoroethyl)amino]-2(5H)-furanone), a member of the new class of butenolide insecticides, contains a novel bioactive scaffold as pharmacophore. It is very versatile in terms of application methods to a variety of crops, exhibits excellent and fast action against a broad spectrum of sucking pest insects including selected neonicotinoid resistant pest populations such as whiteflies and aphids expressing metabolic resistance mechanisms. As a partial agonist flupyradifurone reversibly binds to insect nicotinic acetylcholine receptors (nAChRs) and lacks metabolization by CYP6CM1, a cytochrome P450 over-expressed in cotton whiteflies resistant to imidacloprid and pymetrozine. The butenolide insecticides exhibit structure-activity relationships (SAR) that are different from other nAChR agonists such as the classes of neonicotinoids and sulfoximines. The paper briefly reviews the discovery of the butenolide insecticide flupyradifurone, its SAR differentiating it from established nAChR agonists and a molecular docking approach using the binding site model of CYP6CM1vQ of Bemisia tabaci known to confer metabolic resistance to neonicotinoid insecticides.
authors.affiliation: Bayer CropScience AG, Alfred-Nobel Str. 50, D-40789 Monheim am Rhein, Germany. Electronic address: peter.jeschke@bayer.com.
authors.forename: Peter
authors.initials: P
authors.lastname: Jeschke
authors.affiliation: Bayer CropScience AG, Alfred-Nobel Str. 50, D-40789 Monheim am Rhein, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Nauen
authors.affiliation: Bayer CropScience AG, Alfred-Nobel Str. 50, D-40789 Monheim am Rhein, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Gutbrod
authors.affiliation: Bayer CropScience AG, Alfred-Nobel Str. 50, D-40789 Monheim am Rhein, Germany.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Beck
authors.affiliation: Bayer CropScience AG, Alfred-Nobel Str. 50, D-40789 Monheim am Rhein, Germany.
authors.forename: Svend
authors.initials: S
authors.lastname: Matthiesen
authors.affiliation: Bayer CropScience AG, Alfred-Nobel Str. 50, D-40789 Monheim am Rhein, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Haas
authors.affiliation: Bayer CropScience AG, Alfred-Nobel Str. 50, D-40789 Monheim am Rhein, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Velten
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D019476:Insect Proteins / Q000378:metabolism; D007306:Insecticides / Q000737:chemistry / Q000494:pharmacology; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D018722:Nicotinic Agonists / Q000737:chemistry / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000378:metabolism
chemical_list: D019476:Insect Proteins; D007306:Insecticides; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; C004511:butenolide; D015107:4-Butyrolactone
keywords: Butenolides; Cytochrome P450 CYP6CM1; Flupyradifurone; Mode of action; Neonicotinoid-resistance; Structure–activity relationships