Rehse K, Piechocki D, Schober M, Scheffler H, Reitner N, Unsöld E
Institut für Pharmazie I, Freien Universität Berlin, Germany.
Arch Pharm (Weinheim). 1996 Nov;329(11):511-3. doi: 10.1002/ardp.19963291107.
Five 1,3,4-triazol-1-oles (5a-f) with different alkyl, aryl, and arylalkyl substituents in 2,5-position were synthesized and tested for their antithrombotic properties. The 2,5-dimethyl derivative 5a was most active. 2 h after administration of 60 mg/kg to rats thrombus formation by a laser beam was inhibited by 42% in arterioles and by 33% in venules. At the same dose the blood pressure of SHR rats was slightly (5%) but significantly decreased even 4 h after application of 5a. This pattern of activities suggests a nitric oxide mediated mechanism of action. 1,1'-Azo-bis-ethanone oxime(7)-the synthetic precursor of 5a-inhibited the aggregation of blood platelet (Born test) with an IC50 = 15 mumol/L.
合成了5种在2,5位带有不同烷基、芳基和芳基烷基取代基的1,3,4-三唑-1-醇（5a - f），并对其抗血栓形成特性进行了测试。2,5 - 二甲基衍生物5a活性最高。给大鼠注射60mg/kg后2小时，激光束诱导的小动脉血栓形成受到42%的抑制，小静脉血栓形成受到33%的抑制。在相同剂量下，即使在应用5a后4小时，SHR大鼠的血压也略有（5%）但显著下降。这种活性模式表明其作用机制是由一氧化氮介导的。5a的合成前体1,1'-偶氮 - 双 - 乙酮肟（7）抑制血小板聚集（博恩试验），IC50 = 15μmol/L。
