A novel solution to advance synthesis for nerve agent antidotes

Southwest Research Institute has developed a unique technology (US20230242487A1) that enables the safe and efficient synthesis of organophosphorus nerve agent (OPNA) oxime antidotes. Using this technology, SwRI scientists can not only successfully synthesize currently known highly effective nerve agent countermeasures, but also effectively develop promising new drug candidates to treat nerve agent exposure.

Current treatments for OPNA exposure have not changed significantly since the 1950s. OPNAs are odorless and colorless chemicals that are used in both pesticides as well as in chemical weapons. OPNAs affect the central nervous system by interrupting the signals between nerve cells, which can cause nausea, vomiting, and abdominal cramps upon moderate exposure and finally arrhythmias, loss of consciousness and death upon severe exposure if not properly treated.

An estimated 300,000 deaths per year are caused by OPNA exposure, making this issue a significant threat to both military and civilian populations worldwide.

"Overcoming the difficulties with synthesizing medical countermeasures is a longstanding challenge that SwRI has been actively addressing since the early 1990s. We recently had a breakthrough, developing an innovative manufacturing process that enabled us to develop two highly sought-after antidotes," said SwRI's Dr. Shawn Blumberg, a lead scientist in SwRI's Pharmaceutical and Bioengineering Department. "Using this new methodology, we synthesized Hlö-7 and HI-6, which have strong potential to successfully treat OPNA exposure."

The traditional development process for these complex compounds is challenging, requiring the use of an OSHA-regulated carcinogenic compound as well as limited ways to purify the resulting compounds. SwRI's method circumvents the need for dangerous ingredients and integrates new methods for purification of the antidotes.

SwRI is one of more than 300 industry, government and nonprofit organizations supporting the medical countermeasures sector in the Medical CBRN Defense Consortium (MCDC). This sector was founded to support U.S. Department of Defense needs in areas of infectious diseases, chemical threats, and other medical countermeasures for military personnel.

SwRI's Chemistry and Chemical Engineering Division is ISO 9001:2015 certified, meeting international quality standards for product development from initial design through production and service. SwRI scientists support drug development from discovery to clinical trials in FDA-inspected Current Good Manufacturing Practice facilities.

For more information, visit https://pharmdev.swri.org/.

Provided by Southwest Research Institute