Nicorandil analogues containing NO-donor furoxans and related furazans.
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.
Boschi
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Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche, Farmacologiche, Novara, Italy.
Cena
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C
Di Stilo
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A
Fruttero
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R
Gasco
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A
D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D006146:Guanidines / Q000138:chemical synthesis / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D020108:Nicorandil / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000138:chemical synthesis; D009589:Nitrogen Oxides / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000138:chemical synthesis / Q000494:pharmacology
D006146:Guanidines; D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; D010069:Oxadiazoles; D015221:Potassium Channels; D014665:Vasodilator Agents; C010166:furoxans; D020108:Nicorandil; D011189:Potassium Chloride; C004711:dicyandiamido