Abstract
The synthesis and in vitro vasodilating properties of hybrid compounds in which furoxan (1,2,5-oxadiazole 2-oxide) moieties, endowed with different NO-donor properties, were substituted for the nitroxy function of Nicorandil are reported. The corresponding cyanoguanidine analogues are also considered. This approach has led to a series of vasorelaxing compounds devoid of affinity for K(ATP) channels, whose activity is prevalently due to their ability to activate sGC, at the concentrations of the experiments. Related furazan (1,2,5-oxadiazole) derivatives, unable to release nitric oxide were also prepared and studied for control. The amide analogues of Nicorandil display feeble vasorelaxing action not involving the activation of K+ channels, while in the guanidine analogues, this mechanism seems to underlie this action.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Aorta, Thoracic / physiology
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Endothelium, Vascular / drug effects
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Endothelium, Vascular / physiology
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Guanidines / chemical synthesis
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Guanidines / pharmacology
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Inhibitory Concentration 50
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Male
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Muscle Contraction / drug effects
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Muscle, Smooth, Vascular / drug effects
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Nicorandil / analogs & derivatives
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Nicorandil / chemical synthesis
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Nicorandil / pharmacology*
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Nitric Oxide Donors / chemical synthesis
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Nitrogen Oxides / metabolism
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Nuclear Magnetic Resonance, Biomolecular
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Oxadiazoles / chemical synthesis
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Oxadiazoles / pharmacology*
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Potassium Channels / drug effects
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Potassium Chloride / pharmacology
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Rats
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Rats, Wistar
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Vasodilation / drug effects
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Vasodilator Agents / chemical synthesis
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Vasodilator Agents / pharmacology
Substances
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Guanidines
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Nitric Oxide Donors
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Nitrogen Oxides
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Oxadiazoles
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Potassium Channels
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Vasodilator Agents
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furoxans
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Nicorandil
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Potassium Chloride
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dicyandiamido