Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 55, Issue 23, Pages 10791-10795Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm3015519
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Funding
- Direction Generale de l'Armement [REI-DGA 2009-34-0023, PDH-2-NRBC-4-C-403]
- Institut Universitaire de France
- Agence Nationale pour la Recherche [ANR_06_BLAN_0163, ANR_09_BLAN_0192]
- Defense Threat Reduction Agency (DTRA) [HDTRA1-11-C-0047]
- Region Haute Normandie (Crunch program)
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Pyridinium and bis-pyridinium aldoximes are used as antidotes to reactivate acetylcholinesterase (AChE) inhibited by organophosphorus nerve agents. Herein, we described a series of nine nonquaternary phenyltetrahydroisoquinoline-pyridinaldoxime conjugates more efficient than or as efficient as pyridinium oximes to reactivate VX-, tabun- and ethyl paraoxon-inhibited human AChE. This study explores the structure-activity relationships of this new family of reactivators and shows that 1b-d are uncharged hAChE reactivators with a broad spectrum.
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