基于苯并咪唑的凝血因子Xa抑制剂的设计、合成及体外生物活性
Design, synthesis, and in vitro biological activity of benzimidazole based factor Xa inhibitors.
作者信息
Zhao Z, Arnaiz D O, Griedel B, Sakata S, Dallas J L, Whitlow M, Trinh L, Post J, Liang A, Morrissey M M, Shaw K J
机构信息
Discovery Research, Berlex Biosciences, Richmond, CA 94804-0099, USA.
出版信息
Bioorg Med Chem Lett. 2000 May 1;10(9):963-6. doi: 10.1016/s0960-894x(00)00139-6.
Inhibitors based on the benzimidazole scaffold showed subnanomolar potency against Factor Xa with 500-1000-fold selectivity against thrombin and 50-100-fold selectivity against trypsin. The 2-substituent on the benzimidazole ring had a strong impact on the FXa inhibitory activity. Crystallography studies suggest that the 2-substituent may have a conformational effect favoring the extended binding conformation.
基于苯并咪唑骨架的抑制剂对因子Xa显示出亚纳摩尔级的效力，对凝血酶具有500-1000倍的选择性，对胰蛋白酶具有50-100倍的选择性。苯并咪唑环上的2-取代基对FXa抑制活性有强烈影响。晶体学研究表明，2-取代基可能具有有利于延伸结合构象的构象效应。
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