The role of fluorine in the design of nicotinic acetylcholine receptor (nAChR) competitive modulators

Abstract In the search for an optimal product for modern agricultural chemistry in terms of efficacy, environmental safety, user friendliness, and economic viability, the substitution of molecules with halogen atoms or halogen-containing substituents is an important tool. Besides the impact on biological activity in combination with further structural fragments, depending on the mode of action (MoA), the introduction of fluorine atoms or fluorine-containing substituents into an insecticide can influence (some) specific properties. These include properties such as degradation in soil, metabolism in plants, and target pests, which might result in a favorable compatibility profile with respect to nontarget arthropods or beneficial insects. Since 2004, the importance of fluorine atoms or fluorine-containing substituents in the design of novel nicotinic acetylcholine receptor ( n AChR) competitive modulators (IRAC MoA Classification, Main Group 4) has been increased. This review gives an overview of the role of fluorine in molecules of the commercialized neonicotinoid subgroup 4A in comparison with latest members of the different IRAC subgroups sulfoximines (4C), butenolides (4D), as well as mesoionics (4E).