Gong Y, Pauls H W, Spada A P, Czekaj M, Liang G, Chu V, Colussi D J, Brown K D, Gao J
Department of Medicinal Chemistry, Rhone-Poulenc Rorer, Collegeville, PA 19426-0107, USA.
Bioorg Med Chem Lett. 2000 Feb 7;10(3):217-21. doi: 10.1016/s0960-894x(99)00673-3.
The design, synthesis and SAR of amido-(propyl and allyl)-hydroxybenzamidine coagulation factor Xa inhibitors is described. These achiral inhibitors are selective for fXa vis a vis structurally related serine proteases and are readily prepared in 6-7 linear steps. The most potent member 9j (fXa Ki = 0.75 nM) is selective (>1000-fold) and an effective anticoagulant in mammalian plasma.
本文描述了酰胺基-(丙基和烯丙基)-羟基苯甲脒凝血因子Xa抑制剂的设计、合成及构效关系。这些非手性抑制剂相对于结构相关的丝氨酸蛋白酶对fXa具有选择性,并且易于通过6-7步线性反应制备。活性最强的成员9j(fXa Ki = 0.75 nM)具有选择性(>1000倍),是哺乳动物血浆中的有效抗凝剂。