Koshio Hiroyuki, Hirayama Fukushi, Ishihara Tsukasa, Taniuchi Yuta, Sato Kazuo, Sakai-Moritani Yumiko, Kaku Seiji, Kawasaki Tomihisa, Matsumoto Yuzo, Sakamoto Shuichi, Tsukamoto Shin-ichi
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd, 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
Bioorg Med Chem. 2004 May 1;12(9):2179-91. doi: 10.1016/j.bmc.2004.02.022.
Factor Xa (fXa) is a serine protease involved in the coagulation cascade, which has received great interest as a potential target for the development of new antithrombotic drugs. Herein we report a novel series of fXa inhibitors in which the 1,4-diazepane moiety was designed to interact with the S4 aryl-binding domain of the fXa active site. Compound 13 (YM-96765) showed potent fXa inhibitory activity (IC(50) = 6.8 nM) and effective antithrombotic activity without prolonging bleeding time.
凝血因子Xa（fXa）是一种参与凝血级联反应的丝氨酸蛋白酶，作为新型抗血栓药物开发的潜在靶点受到了广泛关注。在此，我们报道了一系列新型fXa抑制剂，其中1,4 - 二氮杂环庚烷部分被设计用于与fXa活性位点的S4芳基结合域相互作用。化合物13（YM - 96765）表现出强大的fXa抑制活性（IC50 = 6.8 nM）以及有效的抗血栓活性，且不会延长出血时间。
