Discovery and initial structure-activity relationships of trisubstituted ureas as thrombin receptor (PAR-1) antagonists

被引：24
|
作者：
Barrow, JC [1 ]
Nantermet, PG
Selnick, HG
Glass, KL
Ngo, PL
Young, MB
Pellicore, JM
Breslin, MJ
Hutchinson, JH
Freidinger, RM
Condra, C
Karczewski, J
Bednar, RA
Gaul, SL
Stern, A
Gould, R
Connolly, TM
机构：
[1] Merck Res Labs, Dept Med Chem, West Point, PA 19486 USA
[2] Merck Res Labs, Dept Pharmacol, West Point, PA 19486 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 20期
关键词：
D O I：
10.1016/S0960-894X(01)00538-8
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Thrombin is the most potent agonist of platelet activation, and its effects are predominantly mediated by platelet thrombin receptors. Therefore, antagonists of the thrombin receptor have potential utility for the treatment of thrombotic disorders. Screening of combinatorial libraries revealed 2 to be a potent antagonist of the thrombin receptor. Modifications of this structure produced 11k, which inhibits thrombin receptor stimulated secretion and aggregation of platelets. (C) 2001 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码：2691 / 2696
页数：6
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