Diazeniumdiolate Chemistry as a Platform for Designing Nitric Oxide (NO)- and Nitroxyl (HNO)-Based Clinical Applications
Nitric oxide is a potent and multifaceted bioregulatory agent. Named “Molecule of the Year” by Science in 1992, it was the focus of the 1998 Nobel Prize in
Physiology or Medicine. Our research is aimed at targeting NO to specific sites in the body for important therapeutic applications using NO-releasing compounds
called diazeniumdiolates (also known as NONOates). These agents have come into wide use as sources of authentic NO in research applications
requiring reliable fluxes generated in solution with reproducible half-lives ranging from 2 seconds to 20 hours at physiological temperature and pH.
Recently, certain diazeniumdiolates were found to generate nitroxyl (HNO, the one-electron reduction product of NO and another known bioeffector) as well as NO on hydrolysis. Currently,
we are seeking partners to explore the possible clinical benefits of diazeniumdiolate technology, with special emphasis on the indications below.
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Five clinical areas in which diazeniumdiolate-based proof-of-concept studies
suggest considerable practical significance on the part of this class of
compounds. Central to the rational design of improved drugs and devices in
all five of these areas is our vigorous program of basic research into the
fundamental physicochemical properties of compounds bearing the diazeniumdiolate functional group.