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

引用

页码：67 / 72

页数：6