PMID: 9557136Apr 29, 1998Paper

New NO-donors with antithrombotic and vasodilating activities, Part 20. Azodioxides activated by electron acceptors in geminal or vicinal position

Archiv der Pharmazie
K Rehse, M Herpel

Abstract

Twenty-two nitroso compounds with cyano, acyloxy, or carbonyl groups in geminal position were prepared, eight of them for the first time. In the solid state these compounds dimerize to colorless azodioxides. Exceptions are the 4-nitrobenzoyloxynitroso compounds 7b, f, and g which form bright blue crystals. In vitro (Born test, collagen) considerable antiplatelet activity was observed in each class of compounds. Azodioxides with cyano groups in geminal position (3a, b) were most active (IC50 approximately 10 microM) suggesting the importance of strong electron withdrawing groups in geminal position to the azodioxide partial structure. When administered orally to rats (60 mg/kg) all compounds inhibited the thrombus formation in mesenteric arterioles and venules. The acetyloxy derivatives 5d and 5e were most active (18-21% inhibition in arterioles and 11-15% inhibition in venules). In aqueous media at 37 degrees C the cyanonitroso compound 3b and the benzoyloxynitroso compound 7a decomposed to nitric oxide and its reduced form nitrosohydrogen. This suggests that the above pharmacological effects are mediated by a NO dependent mechanism.

Citations

Jan 18, 2011·Antioxidants & Redox Signaling·Jenna F DuMond, S Bruce King
Jul 2, 2004·Organic Letters·Géraldine CalvetCyrille Kouklovsky
Nov 3, 2017·Medicinal Research Reviews·Catarina OliveiraFernanda Borges
Dec 22, 2015·Coordination Chemistry Reviews·Debashree BasudharDavid A Wink
Apr 11, 2002·Chemical Reviews·Peng George WangAdam J Janczuk
Jan 17, 2009·The Journal of Organic Chemistry·Harinath ChakrapaniEric J Toone
Aug 2, 2018·The Journal of Organic Chemistry·Aleksandr O KokuevSema L Ioffe

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