Miyamae T, Hashizume H, Ogawa T, Okayama T, Nukui E, Oshima K, Morikawa T, Hagiwara M
Research Institute, Fuji Chemical Industries Co., Ltd., Toyama, Japan.
Arzneimittelforschung. 1997 Jan;47(1):13-8.
The new compound 3-[2-([1,1':2,1"]-terphenyl-4'yl)ethyl]phenoxyacetic acid (F1070) was synthesized and its effects on platelet aggregation induced by thrombin, thrombin receptor agonist peptide (TRAP), ADP and collagen were evaluated in humans, guinea pigs and rats, and were compared with the effects of he thrombin antagonists argipidine and (D)Phe-Pro-Arg-CH2Cl (FPR). F1070 inhibited the platelet aggregation induced by these agonists and was highly selective in its inhibition of thrombin. F1070 inhibited fibrin formation induced by thrombin, but far less effectively than argipidine. In a guinea pig model of extracorporeal circulation thrombosis, F1070 (10 mg/kg p.o.) significantly inhibited the development of a thrombus. F1070 is thus a key compound that should facilitate the development of new orally active antithrombotic drugs that are specific for thrombin.
合成了新化合物3-[2-([1,1':2,1"]-三联苯-4'-基)乙基]苯氧基乙酸(F1070)，并在人、豚鼠和大鼠中评估了其对凝血酶、凝血酶受体激动肽(TRAP)、ADP和胶原诱导的血小板聚集的影响，并与凝血酶拮抗剂阿吉匹定和(D)Phe-Pro-Arg-CH2Cl(FPR)的作用进行了比较。F1070抑制这些激动剂诱导的血小板聚集，并且在抑制凝血酶方面具有高度选择性。F1070抑制凝血酶诱导的纤维蛋白形成，但效果远不如阿吉匹定。在豚鼠体外循环血栓形成模型中，F1070(10mg/kg口服)显著抑制血栓形成。因此，F1070是一种关键化合物，应有助于开发新的对凝血酶具有特异性的口服活性抗血栓药物。
