Furoxans as nitric oxide donors. 4-Phenyl-3-furoxancarbonitrile: thiol-mediated nitric oxide release and biological evaluation

J Med Chem. 1994 Dec 9;37(25):4412-6. doi: 10.1021/jm00051a020.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / physiology
  • Enzyme Activation / drug effects
  • Guanosine Monophosphate / pharmacology
  • Guanylate Cyclase / metabolism
  • Humans
  • Lung / enzymology
  • Male
  • Mass Spectrometry
  • Nitric Oxide / chemistry*
  • Norepinephrine / pharmacology
  • Oxadiazoles / chemistry*
  • Oxadiazoles / pharmacology
  • Phenols / chemistry*
  • Platelet Aggregation Inhibitors / chemistry
  • Platelet Aggregation Inhibitors / pharmacology
  • Rats
  • Rats, Wistar
  • Sulfhydryl Compounds*
  • Vasodilation / drug effects
  • Vasodilator Agents / chemistry
  • Vasodilator Agents / pharmacology

Substances

  • 4-phenyl-3-furoxancarbonitrile
  • Oxadiazoles
  • Phenols
  • Platelet Aggregation Inhibitors
  • Sulfhydryl Compounds
  • Vasodilator Agents
  • Nitric Oxide
  • thiophenol
  • Guanosine Monophosphate
  • Guanylate Cyclase
  • Norepinephrine