Rehse K, Brehme F
Institut für Pharmazie I, Freie Universität Berlin, Germany.
Arch Pharm (Weinheim). 1998 Dec;331(12):375-9. doi: 10.1002/(sici)1521-4184(199812)331:12<375::aid-ardp375>3.0.co;2-f.
Seventeen amidoximes (2a-q) comprising aliphatic (2a-d), aromatic (2e-n), and bis compounds (2o-q) have been synthesized. In the Born test 4-chlorophenylethenecarboxamidoxime (21) was most active and inhibited the blood platelet aggregation induced by collagen with an IC50 = 3 microM. After oral administration to rats (60 mg/kg) fourteen compounds significantly inhibited the formation of thrombi in arterioles and venules. The strongest effect was observed with ethene-bis-carboxamidoxime (2q) (31% in arterioles and 18% in venules). The O-ethoxycarbonylderivatives 3 and the corresponding 1,2,4-oxadiazol-5-ones 4, which had been synthesized as prodrugs, showed smaller antithrombotic effects.
已合成了17种偕胺肟（2a - q），包括脂肪族（2a - d）、芳香族（2e - n）和双化合物（2o - q）。在博恩试验中，4 - 氯苯乙烯甲脒肟（21）活性最高，能抑制胶原蛋白诱导的血小板聚集，IC50 = 3微摩尔。给大鼠口服（60毫克/千克）后，14种化合物显著抑制小动脉和小静脉中血栓的形成。乙烯双甲脒肟（2q）的效果最强（小动脉中为31%，小静脉中为18%）。作为前药合成的O - 乙氧羰基衍生物3和相应的1,2,4 - 恶二唑 - 5 - 酮4显示出较小的抗血栓作用。
