Synthesis, evaluation, and crystallographic analysis of L-371,912: A potent and selective active-site thrombin inhibitor

被引：51
作者：
Lyle, TA
Chen, ZG
Appleby, SD
Freidinger, RM
Gardell, SJ
Lewis, SD
Li, Y
Lyle, EA
Lynch, JJ
Mulichak, AM
Ng, AS
NaylorOlsen, AM
Sanders, WM
机构：
[1] MERCK SHARP & DOHME RES LABS,DEPT BIOL CHEM,W POINT,PA 19486
[2] MERCK SHARP & DOHME RES LABS,DEPT MOL DESIGN & DIVERS,W POINT,PA 19486
[3] MERCK SHARP & DOHME RES LABS,DEPT PHARMACOL,W POINT,PA 19486
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1997年 / 7卷 / 01期
关键词：
D O I：
10.1016/S0960-894X(96)00583-5
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Removal of the beta-ketoamide functionality from L370,518 (K-i = 0.09 nM) provided a 5 nM K-i inhibitor of thrombin: L-371,912. Comparison of the enzyme-inhibitor crystal structures suggests a possible explanation for the relatively small change in affinity for thrombin. L-371,912 is selective for thrombin over related serine proteases and is efficacious in an animal model of arterial thrombosis. Copyright (C) 1996 Elsevier Science Ltd
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页码：67 / 72
页数：6
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