Development of N-Substituted Hydroxylamines as Efficient Nitroxyl (HNO) Donors

作者：Guthrie Daryl A; Kim Nam Y; Siegler Maxime A; Moore Cathy D; Toscano John P^*

来源：Journal of the American Chemical Society, 2012, 134(4): 1962-1965.

DOI：10.1021/ja2103923

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 degrees C of 0.7 and 9.5 min, respectively.

• 出版日期2012-2-1