Flupyradifurone (Sivanto™) and its novel butenolide pharmacophore: Structural considerations☆

Abstract Flupyradifurone (4-[(2,2-difluoroethyl)amino]-2(5 H )-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 ( n AChRs) 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 n AChR 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 n AChR agonists and a molecular docking approach using the binding site model of CYP6CM1vQ of Bemisia tabaci known to confer metabolic resistance to neonicotinoid insecticides.