Decomposition of FK 409, a new vasodilator: Identification of nitric oxide as a metabolite

• Published in: Bioorganic & medicinal chemistry letters Vol. 5; no. 9; pp. 973 - 978
• Main Authors: Décout, Jean-Luc, Roy, Béatrice, Fontecave, Marc, Muller, Jean-Claude, Williams, Paul Howard, Loyaux, Denis
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 04.05.1995
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/0960-894X(95)00148-M

(±)-(3E)-4-Ethyl-2-hydroxyimino-5-nitro-3-hexenamide, FK 409, is a natural product selected for its strong vasorelaxant properties. In neutral aqueous solution, it decomposes spontaneously giving rise to a diketone as shown by HPLC and mass spectrometry. Also, during decomposition, nitric oxide intermediate formation was demonstrated by EPR 1 spectroscopy specific assays. An analog of FK 409, in which the oxime group was selectively hydrolyzed, has lost the ability to generate NO and shows reduced vasorelaxant potency. These results provide a molecular basis for the vasorelaxant effects of FK 409. FK 409 is known for its strong vasorelaxant properties. In water, it decomposes spontaneously into 1, as shown by HPLC and mass spectrometry, with parallel formation of nitric oxide, as demonstrated by EPR spectroscopy. The analog 2 does not generate NO and shows reduced vasorelaxant potency. These results provide a molecular basis for the vasorelaxant effects of FK 409.