Rehse K, König P
Institut für Pharmazie, Freien Universität Berlin.
Arch Pharm (Weinheim). 1995 Feb;328(2):137-42. doi: 10.1002/ardp.19953280209.
Mesoionic 1,2,3,4-oxatriazolimines and the corresponding oxatriazolones were prepared and tested for their antiplatelet and antithrombotic activities. In the Born-test 5-amino-3-phenyl-1,2,3,4-oxatriazolimine chloride inhibited the platelet aggregation halfmaximally in a concentration of 50 nmol/L. Its N-ethoxycarbonyl derivative inhibited thrombus formation in arterioles of rats by 48% (10 mg/kg, 2 h after p.o. administration). These effects appear to be related to the formation of intermediate nitrosohydrazine derivatives. This aspect was supported by the activities in noncyclic nitrosohydrazines (2 compds.), nitrosohydrazones (2) and nitrosohydrazides (11). Five of them exhibited an IC50 < 100 nmol/L in the Born-test. In a thrombotic model strong inhibition of thrombus formation was observed after intravenous application. The 1-nitroso-1-benzylhydrazine even exhibited strong inhibitory effects after oral administration.
制备了中氮茚1,2,3,4-恶三唑啉及其相应的恶三唑酮，并对其抗血小板和抗血栓活性进行了测试。在博恩试验中，5-氨基-3-苯基-1,2,3,4-恶三唑啉氯化物在浓度为50 nmol/L时可最大程度地抑制血小板聚集的一半。其N-乙氧羰基衍生物可使大鼠小动脉中的血栓形成减少48%（口服给药10 mg/kg，2小时后）。这些作用似乎与中间亚硝基肼衍生物的形成有关。非环状亚硝基肼（2种化合物）、亚硝基腙（2种）和亚硝基酰肼（11种）的活性支持了这一方面。其中五种在博恩试验中表现出IC50 < 100 nmol/L。在血栓形成模型中，静脉给药后观察到对血栓形成的强烈抑制作用。1-亚硝基-1-苄基肼口服给药后甚至表现出强烈的抑制作用。
