Rehse K, Kämpfe M, Schleifer K J
Institut für Pharmazie der Freien Universität Berlin.
Arch Pharm (Weinheim). 1993 Aug;326(8):483-7. doi: 10.1002/ardp.19933260811.
Nine nitrosimino title compounds were prepared. They inhibit the aggregation of human platelets induced by collagen with an IC50 = 0.7--33 mumol/L. The most active substance is the 3-phenylethyl derivative 6b. The in vitro effect is mediated by an active metabolite which is formed by a photochemical reaction in the aggregometer. As the corresponding and so far unknown sydnone-5-cyanimines have no effect on platelets the metabolite is most certainly a NO-species. The activity of the sydnone-5-nitrimine 5b is in the same order of magnitude (IC50 = 7.5 mumol/L) as in the nitrosimines of type 6. The most active compound 6b was investigated for antithrombotic properties in a thrombosis model, where the thrombus formation was induced by a laser-beam. 2 h after oral administration of 60 mg/kg of 6b to rats in venoles a 28% inhibition of thrombin formation was found. In arterioles this effect is more evident and a 48% inhibition is seen (the thrombus formation index is 2.6 and 3.9, respectively). These results suggest that the active metabolite is formed as well in vivo.
制备了九种亚硝基氨基标题化合物。它们抑制胶原蛋白诱导的人血小板聚集，IC50 = 0.7 - 33 μmol/L。活性最强的物质是3-苯乙基衍生物6b。体外作用由一种活性代谢物介导，该代谢物在血小板聚集仪中通过光化学反应形成。由于相应的且迄今为止未知的sydnone - 5 - 氰胺对血小板无作用，所以该代谢物极有可能是一种含氮氧化物。sydnone - 5 - 硝亚胺5b的活性与6型亚硝基胺处于同一数量级（IC50 = 7.5 μmol/L）。对活性最强的化合物6b在血栓形成模型中进行抗血栓特性研究，该模型中血栓形成由激光束诱导。给大鼠静脉注射60 mg/kg的6b后2小时，发现凝血酶形成受到28%的抑制。在小动脉中这种作用更明显，抑制率为48%（血栓形成指数分别为2.6和3.9）。这些结果表明活性代谢物在体内也能形成。
