Development of N-substituted hydroxylamines as efficient nitroxyl (HNO) donors.
Due to its inherent reactivity, nitroxyl (HNO), must be generated in situ through the use of donor compounds, but very few physiologically useful HNO donors exist. Novel N-substituted hydroxylamines with carbon-based leaving groups have been synthesized, and their structures confirmed by X-ray crystallography. These compounds generate HNO under nonenzymatic, physiological conditions, with the rate and amount of HNO released being dependent mainly on the nature of the leaving group. A barbituric acid and a pyrazolone derivative have been developed as efficient HNO donors with half-lives at pH 7.4, 37 °C of 0.7 and 9.5 min, respectively.
Department of Chemistry, 3400 North Charles Street, Johns Hopkins University, Baltimore, Maryland 21218, USA.
Daryl A
DA
Guthrie
Nam Y
NY
Kim
Maxime A
MA
Siegler
Cathy D
CD
Moore
John P
JP
Toscano
D018360:Crystallography, X-Ray; D006898:Hydroxylamines / Q000138:chemical synthesis / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D009589:Nitrogen Oxides / Q000138:chemical synthesis* / Q000737:chemistry
D006898:Hydroxylamines; D009589:Nitrogen Oxides; C039900:nitroxyl