title: Kinetic assessment of N-methyl-2-methoxypyridinium species as phosphonate anion methylating agents.
abstract: Organophosphate nerve agents and pesticides are potent inhibitors of acetylcholinesterase (AChE). Although oxime nucleophiles can reactivate the AChE-phosphyl adduct, the adduct undergoes a reaction called aging. No compounds have been described that reactivate the aged-AChE adduct. A family of 2-methoxypyridinium species which reverse aging in a model system is presented. A kinetic study of this system, which includes an SAR analysis, demonstrates that the reaction is highly tunable based on the ring substituents.
authors: Department of Chemistry, The University of Iowa, Iowa City, Iowa 52242, USA.
authors: Joseph J
authors: JJ
authors: Topczewski
authors: Daniel M
authors: DM
authors: Quinn
mesh_terms: D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D007700:Kinetics; D008956:Models, Chemical; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000737:chemistry* / Q000494:pharmacology; D010091:Oximes / Q000737:chemistry / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D009943:Organophosphorus Compounds; D010091:Oximes; D011726:Pyridinium Compounds