Rehse K, Herpel M
Institut für Pharmazie I, Freie Universität Berlin, Germany.
Arch Pharm (Weinheim). 1998 Mar;331(3):104-10. doi: 10.1002/(sici)1521-4184(199803)331:3<104::aid-ardp104>3.0.co;2-r.
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.
制备了22种偕位带有氰基、酰氧基或羰基的亚硝基化合物，其中8种为首次制备。这些化合物在固态下二聚形成无色偶氮二氧化物。例外的是4-硝基苯甲酰氧基亚硝基化合物7b、f和g，它们形成亮蓝色晶体。在体外（博恩试验、胶原蛋白），每类化合物均观察到显著的抗血小板活性。偕位带有氰基的偶氮二氧化物（3a、b）活性最高（IC50约为10微摩尔），这表明偕位上的强吸电子基团对于偶氮二氧化物部分结构很重要。当以60毫克/千克的剂量口服给予大鼠时，所有化合物均抑制肠系膜小动脉和小静脉中的血栓形成。乙酰氧基衍生物5d和5e活性最高（小动脉中抑制率为18 - 21%，小静脉中抑制率为11 - 15%）。在37℃的水性介质中，氰基亚硝基化合物3b和苯甲酰氧基亚硝基化合物7a分解为一氧化氮及其还原形式亚硝基氢。这表明上述药理作用是由一种依赖一氧化氮的机制介导的。
