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 cryst...

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Veröffentlicht in:Journal of the American Chemical Society 2012-02, Vol.134 (4), p.1962-1965
Hauptverfasser: Guthrie, Daryl A, Kim, Nam Y, Siegler, Maxime A, Moore, Cathy D, Toscano, John P
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Sprache:eng
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Zusammenfassung: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.
ISSN:0002-7863
1520-5126
DOI:10.1021/ja2103923