Rehse K, Brehme F
Institut für Pharmazie I, Freie Universität Berlin, Berlin, Germany.
Arch Pharm (Weinheim). 2000 Jun;333(6):157-61. doi: 10.1002/1521-4184(20006)333:6<157::aid-ardp157>3.0.co;2-c.
Eleven azide oximes were prepared and tested for their antiplatelet (in vitro), antithrombotic, and blood pressure lowering activities. Nine of them inhibited the aggregation of blood platelets (Born test, inducer collagen) with IC50 values between 10 and 50 microM. The most active compounds i.e. azido-4-nitrophenylbenzaldoxime (2h) had an IC50 = 2 microM. Nine azide oximes exhibited significant antithrombotic properties. The most active compounds were 2h and 2c (azido-4-methylphenylbenzaldoxime) with an inhibition of thrombus formation above 20% in arterioles after a single p.o. dose of 60 mg/kg. Both compounds lowered the blood pressure in spontaneously hypertensive rats by 11% (2h) or 5% (2c), respectively. Seven azide oximes were rearranged to the title tetrazololes which however showed smaller antithrombotic effects. In separate in vitro experiments at 37 degrees C it could be demonstrated that azide oximes release nitric oxide (conversion rate approximately 10%.h-1) and nitrosohydrogen (conversion rate approximately 2%.h-1). This makes it appear probable that the above effects are mediated by these molecules.
制备了11种叠氮肟，并对其抗血小板（体外）、抗血栓形成和降血压活性进行了测试。其中9种抑制血小板聚集（博恩试验，诱导剂胶原蛋白），IC50值在10至50微摩尔之间。活性最高的化合物即叠氮基-4-硝基苯甲醛肟（2h）的IC50 = 2微摩尔。9种叠氮肟表现出显著的抗血栓形成特性。活性最高的化合物是2h和2c（叠氮基-4-甲基苯甲醛肟），单次口服剂量60毫克/千克后，在小动脉中血栓形成的抑制率超过20%。这两种化合物分别使自发性高血压大鼠的血压降低了11%（2h）或5%（2c）。7种叠氮肟重排为标题中的四唑，但显示出较小的抗血栓形成作用。在37℃的单独体外实验中可以证明，叠氮肟释放一氧化氮（转化率约为10%·h-1）和亚硝基氢（转化率约为2%·h-1）。这使得上述作用很可能是由这些分子介导的。
