Furoxans as nitric oxide donors. 4-Phenyl-3-furoxancarbonitrile: thiol-mediated nitric oxide release and biological evaluation.
4-Phenyl-3-furoxancarbonitrile (2) affords nitric oxide under the action of thiol cofactors. Two principal products were isolated in the reaction with thiophenol: the phenylcyanoglyoxime (6) and 5-amino-3-phenyl-4-(phenylthio)isoxazole (7). Mechanisms which could account for the formation of these two products are discussed. Compound 2 is an efficient activator of the rat lung soluble guanylate cyclase, displays high vasodilatory activity on strips of rat thoracic aorta precontracted with noradrenaline, and is a potent inhibitor of platelet aggregation.
Medana
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Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi, Torino, Italy.
Ermondi
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G
Fruttero
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R
Di Stilo
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A
Ferretti
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C
Gasco
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D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D006157:Guanosine Monophosphate / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000201:enzymology; D008297:Male; D013058:Mass Spectrometry; D009569:Nitric Oxide / Q000737:chemistry*; D009638:Norepinephrine / Q000494:pharmacology; D010069:Oxadiazoles / Q000737:chemistry* / Q000494:pharmacology; D010636:Phenols / Q000737:chemistry*; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000737:chemistry / Q000494:pharmacology
C090933:4-phenyl-3-furoxancarbonitrile; D010069:Oxadiazoles; D010636:Phenols; D010975:Platelet Aggregation Inhibitors; D013438:Sulfhydryl Compounds; D014665:Vasodilator Agents; D009569:Nitric Oxide; C042983:thiophenol; D006157:Guanosine Monophosphate; D006162:Guanylate Cyclase; D009638:Norepinephrine