Production of HNO From Derivatized DiazeniumdiolatesTechnology #ua10-115
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Treating Disease and Pain using Nitroxyl (HNO) Releasing Compounds
A compound has been developed for releasing controlled fluxes of HNO in physiological media or conditions. The compound undergoes a slow hydrolysis at physiological pH, such that it generates a correspondingly lower steady-state concentration of HNO, minimizing its dimerization/dehydration to N2O. As a result the compound can provide increased efficacy against pain, cancer, or cardiovascular disease.
Nitroxyl (HNO) is an elusive chemical species that has been shown to possess intriguing biological properties. For example, nitroxyl has been implicated in the mechanism of cyanamide’s inhibitory effect on aldehyde dehydrogenase in treating alcohol abuse as well as reversing experimental heart failure. Despite HNO having been described in the chemical literature for decades, there are surprising gaps in the literature that complicate the rational exploitation of its pharmacological properties. Historically, Angeli’s salt (AS) has been known to generate HNO in solution. Recently, IPA/NO (1, the sodium salt of diazeniumdiolated isopropylamine) has been shown to mimic AS in its chemical and biological properties. Unfortunately, neither of these salts are suitable from the drug development perspective since both are difficult to purify.