Abstract
1-(7-Azabenzobicyclo[2.2.1]heptane)diazen-1-ium-1,2-diolate (16) was designed with the expectation that it would act as a dual nitric oxide (NO) and nitroxyl (HNO) donor that is not carcinogenic or genotoxic. Compound 16, with a suitable half-life (17.8min) in PBS at pH 7, released NO (19%) and HNO (22%) during a 2h incubation in PBS at pH 7. In addition, compound 16 exhibited a significant in vitro positive inotropic effect, increased the rates of contraction and relaxation, and increased coronary flow rate, but did not induce a chronotropic effect. Furthermore, compound 16 (13.7mgkg−1, po dose) provided a significant reduction in the blood pressure of mice up to 3h post-drug administration. All these data suggest that compound 16 constitutes an attractive ‘lead-compound’ that could have potential applications to treat cardiovascular disease(s) such as congestive heart failure.
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