大环因子Xa抑制剂
Macrocyclic factor XIa inhibitors.
作者信息
Wang Cailan, Corte James R, Rossi Karen A, Bozarth Jeffrey M, Wu Yiming, Sheriff Steven, Myers Joseph E, Luettgen Joseph M, Seiffert Dietmar A, Wexler Ruth R, Quan Mimi L
机构信息
Bristol-Myers Squibb Company, Research and Development, 350 Carter Road, Hopewell, NJ 08540 United States.
Bristol-Myers Squibb Company, Research and Development, 311 Pennington-Rocky Hill Road, Pennington, NJ 08543-2130 United States.
出版信息
Bioorg Med Chem Lett. 2017 Sep 1;27(17):4056-4060. doi: 10.1016/j.bmcl.2017.07.048. Epub 2017 Jul 25.
A series of macrocyclic factor XIa (FXIa) inhibitors was designed based on an analysis of the crystal structures of the acyclic phenylimidazole compounds. Further optimization using structure-based design led to inhibitors with pM affinity for FXIa, excellent selectivity against a panel of relevant serine proteases, and good potency in the activated partial thromboplastin time (aPTT) clotting assay.
基于对无环苯基咪唑化合物晶体结构的分析，设计了一系列大环因子Xla（FXIa）抑制剂。利用基于结构的设计进行进一步优化，得到了对FXIa具有皮摩尔亲和力、对一系列相关丝氨酸蛋白酶具有优异选择性且在活化部分凝血活酶时间（aPTT）凝血试验中具有良好效力的抑制剂。
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