Thrombin receptor (PAR-1) antagonists. Heterocycle-based peptidomimetics of the SFLLR agonist motif

被引：32
|
作者：
Hoekstra, WJ [1 ]
Hulshizer, BL
McComsey, DF
Andrade-Gordon, P
Kauffman, JA
Addo, MF
Oksenberg, D
Scarborough, RM
Maryanoff, BE
机构：
[1] RW Johnson Pharmaceut Res Inst, Spring House, PA 19477 USA
[2] COR Therapeut Inc, S San Francisco, CA 94080 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1998年 / 8卷 / 13期
关键词：
D O I：
10.1016/S0960-894X(98)00292-3
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
The thrombin receptor (PAR-I) is activated by a-thrombin to stimulate various cell types, including platelets, through the tethered-ligand sequence SFLLRN. A series of azole-based carboxamides, designed after SFLLR, were synthesized and evaluated in vitro. The compounds inhibited platelet aggregation induced by SFLLRN-NH2 or a-thrombin, and blocked the binding of [H-3]-S-(p-F-Phe)-Har-L-Har-KY-NH2 to a CHRF membrane preparation of PAR-I. Oxazole 30 bound to PAR-I with an IC50 Of 1.6 mu M, and gave IC50 values of 25 mu M and 6.6 mu M against alpha-thrombin- and SFLLRN-NH2-induced platelet aggregation, respectively. (C) 1998 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码：1649 / 1654
页数：6
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