Journal
ACS MEDICINAL CHEMISTRY LETTERS
Volume 10, Issue 5, Pages 761-766Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsmedchemlett.9b00021
Keywords
Acetylcholinesterase; VX; HLo; -7; nerve agent; organophosphate; reactivator
Categories
Funding
- Defense Threat Reduction Agency [3889, 3943, 10243]
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The threat of a deliberate release of chemical nerve agents has underscored the need to continually improve field effective treatments for these types of poisonings. The oxime containing HLO-7 is a potential second-generation therapeutic reactivator. A synthetic process for HLO-7 is detailed with improvements to the DIBAL reduction and ion exchange steps. HLo-7 was visualized for the first time within the active site of human acetylcholinesterase and its relative ex vivo potency confirmed against various nerve agents using a phrenic nerve hemidiaphragm assay.
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