Novel thrombin inhibitors incorporating non-basic partially saturated heterobicyclic P1-arginine mimetics

被引：22

作者：

Peterlin-Masic, L

Mlinsek, G

Solmajer, T

Trampus-Bakija, A

Stegnar, M

Kikelj, D

机构：

[1] Univ Ljubljana, Fac Pharm, Ljubljana 1000, Slovenia

[2] Natl Inst Chem, Ljubljana 1115, Slovenia

[3] Lek Pharmaceut Dd, Drug Discovery, Ljubljana 1526, Slovenia

[4] Univ Ljubljana, Med Ctr, Dept Angiol, Ljubljana 1000, Slovenia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 05期

关键词：

D O I：

10.1016/S0960-894X(03)00030-1

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The design, synthesis and biological activity of non-covalent thrombin inhibitors incorporating 4,5,6,7-tetrahydroindazole, 2-methyl-4,5,6,7-tetrahydroindazole, 4,5,6,7-tetrahydroisoindole, 5,6,7,8-tetrahydroquinazoline and 5,6,7,8-tetrahydroquinazolin-2-amine as novel, partially saturated, heterobicyclic P-1-arginine side-chain mimetics is described. The binding mode of the most potent candidate in the series co-crystallized with human alpha-thrombin, which exhibited an in vitro K-i of 140nM and more that 478-fold selectivity against trypsin, is discussed. (C) 2003 Elsevier Science Ltd. All rights reserved.

引用

收藏

页码：789 / 794

页数：6

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