학술논문
O2-SulfonylethylProtected Isopropylamine Diazen-1-ium-1,2-diolates as Nitroxyl (HNO)Donors: Synthesis, β-Elimination Fragmentation, HNO Release,Positive Inotropic Properties, and Blood Pressure Lowering Studies.
Document Type
Article
Author
Source
Subject
*SULFONYL compounds
*ISOPROPYLAMINE
*NITROXYL
*REGULATION of blood pressure
*ELIMINATION reactions
*METHYL vinyl ketone
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Language
ISSN
0022-2623
Abstract
New types of nonexplosive O2-sulfonylethylprotected (-CH2CH2SO2R; R = OMe,NHOMe, NHOBn, Me) derivatives of isopropylamine diazen-1-ium-1,2-diolate(IPA/NO) (2–5) were developed thatare designed to act as novel HNO donors. These compounds, with suitablehalf-lives (6.6–17.1 h) at pH 7.4, undergo a base-induced β-eliminationreaction that releases a methyl vinyl sulfone product and the parentIPA/NO anion which subsequently preferentially releases HNO (46–61%range). Importantly, the O2-methylsulfonylethylcompound 5exhibited a significant in vitro inotropiceffect up to 283% of the baseline value and increased the rates ofcontraction and relaxation but did not induce a chronotropic effect.Furthermore, compound 5(22.5 mg/kg po dose) provideda significant reduction in blood pressure up to 6 h after drug administration.All these data suggest that O2-sulfonylethylprotected derivatives of IPA/NO, which are efficient HNO donors, couldhave potential applications to treat cardiovascular disease(s) suchas congestive heart failure. [ABSTRACT FROM AUTHOR]