Synthesis and Molecular Properties of Nerve Agent Reactivator HLö-7 Dimethanesulfonate

ACS Med Chem Lett. 2019 Mar 28;10(5):761-766. doi: 10.1021/acsmedchemlett.9b00021. eCollection 2019 May 9.


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 HLö-7 is a potential second-generation therapeutic reactivator. A synthetic process for HLö-7 is detailed with improvements to the DIBAL reduction and ion exchange steps. HLö-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.