Journal
ORGANIC LETTERS
Volume 15, Issue 5, Pages 1084-1087Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ol400054m
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Funding
- CounterACT Program, National Institutes of Health Office of the Director
- National Institute of Neurological Disorders and Stroke [5 R21 N5076430]
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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.
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