#C13496
Inventor(s): John Toscano, Daryl Guthrie, Vince Kalish, Fredrick A. Brookfield, Stephen M. Courtney, Lisa M. Frost, Carl L. North
Unmet Need
An estimated 17.9 million people died from cardiovascular diseases in 2019, representing 32% of all global deaths (see WHO). Nitroglycerin has been used as a vasodilator to treat heart conditions for over 130 years. It wasn't until 2003 that scientists realized the beneficial effect was due to it being converted by the body to nitric oxide (NO). Nitroxyl (HNO) chemistry, which was largely ignored over the course of the 20th century, has experienced a resurgence since HNO and NO are redox-related. Treatment with HNO could provide a route as a drug treatment for cardiovascular disease. Due to its inherent reactivity, however, HNO cannot be used directly, and therefore must be generated within the body through the use of prodrugs. Therefore, there is a strong need to develop HNO prodrug compounds where the time scale for release within the body can be controlled by the chemistry.
Technology Overview
Researchers at Johns Hopkins have developed a pyrazolone derivative class of molecules that donate HNO under non-enzymatic, physiological conditions. Pyrazolone derivatives release HNO at a controlled rate, and the rate of HNO release is modulated by varying the nature and location of functional groups on the compounds. HNO has a short half-life in the body, so being able to control its release rate is desirable as a potential drug treatment.
Stage of Development
Compounds synthesized and characterized.
Publications
Daryl A. Guthrie, et al. Development of N-Substituted Hydroxylamines as Efficient Nitroxyl
(HNO) Donors. J. Am. Chem. Soc. 2012, 134, 1962-1965
Daryl A. Guthrie, et al. “Catch and Release” of HNO with Pyrazolones. J. Org. Chem. 2015, 80, 1338-1348.
