Abstract
New types of nonexplosive O-2-sulfonylethyl protected (-CH2CH2SO2R; R = OMe, NHOMe, NHOBn, Me) derivatives of isopropylamine diazen-1-ium-1,2-diolate (IPA/NO) (2-5) were developed that are designed to act as novel HNO donors. These compounds, with suitable half lives (6.6-17.1 h) at pH 7.4, undergo a base induced beta-elimination reaction that releases a methyl vinyl sulfone product and the, parent IPA/NO anion which subsequently preferentially releases HNO (46-61% range). Importantly, the O-2-methylsulfonylethyl compound 5 exhibited a significant in vitro inotropic effect up to 283% of the baseline value and increased the rates of contraction and relaxation but did not induce a chronotropic effect. Furthermore; compound 5 (22.5 mg/kg po dose). provided a significant reduction in blood pressure up to 6 h after drug administration. All these data suggest that O-2-sulfonylethyl protected derivatives of IPA/NO, which are efficient HNO donors, could have potential applications to treat cardiovascular disease(s) such as congestive heart failure.