Satyanarayana K, Rehse K
Institut für Pharmazie I, Freie Universität Berlin, Germany.
Arch Pharm (Weinheim). 1998 Jun;331(6):207-10. doi: 10.1002/(sici)1521-4184(199806)331:6<207::aid-ardp207>3.0.co;2-5.
Twenty eight organic azides were synthesized and tested for their antithrombotic and blood pressure lowering activities in rats (60 mg/kg, p.o.). In fifteen compounds significant antithrombotic effects were observed. In thirteen cases a significant lowering of the blood pressure of spontaneously hypertensive rats (SHR) was seen. The peak activities in both systems were found for hexyl azide (4), 2-phenylethyl azide (14), and 4-pyridinecarboxylic acid azide (23). In these compounds the inhibition of thrombus formation in mesenteric arterioles was > 20%. The lowering of blood pressure was > 10% and long lasting (> 6 h) in 4 and 14 while 23 had a shorter duration of action (approximately 4 h). In two classes of azides, namely branched aliphatic azides (e.g. 2-azidopentane 9) and aliphatic carbonyl derivatives (e.g. benzoyl-azido-methane 17), only antithrombotic properties were observed. A lack of endothelial metabolism is suggested to be the reason for this therapeutically favorable behaviour.
合成了28种有机叠氮化物，并在大鼠中（口服，60mg/kg）测试了它们的抗血栓形成和降血压活性。在15种化合物中观察到了显著的抗血栓形成作用。在13种情况下，自发性高血压大鼠（SHR）的血压出现了显著降低。在己基叠氮化物（4）、2-苯乙基叠氮化物（14）和4-吡啶羧酸叠氮化物（23）中发现了这两种系统中的峰值活性。在这些化合物中，肠系膜小动脉中血栓形成的抑制率>20%。化合物4和14的血压降低>10%且持续时间长（>6小时），而化合物23的作用持续时间较短（约4小时）。在两类叠氮化物中，即支链脂肪族叠氮化物（如2-叠氮基戊烷9）和脂肪族羰基衍生物（如苯甲酰叠氮基甲烷17），仅观察到抗血栓形成特性。缺乏内皮代谢被认为是这种治疗上有利行为的原因。
