Azaindoles: Moderately basic P1 groups for enhancing the selectivity of thrombin inhibitors

被引：29

作者：

Sanderson, PEJ ^{[1
]}

Stanton, MG

Dorsey, BD

Lyle, TA

McDonough, C

Sanders, WM

Savage, KL

Naylor-Olsen, AM

Krueger, JA

Lewis, SD

Lucas, BJ

Lynch, JJ

Yan, YW

机构：

[1] Merck Res Labs, Dept Med Chem, West Point, PA 19486 USA

[2] Merck Res Labs, Dept Mol Syst, West Point, PA 19486 USA

[3] Merck Res Labs, Dept Biol Chem, West Point, PA 19486 USA

[4] Merck Res Labs, Dept Pharmacol, West Point, PA 19486 USA

[5] Merck Res Labs, Dept Biol Struct, West Point, PA 19486 USA

来源：

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

关键词：

D O I：

10.1016/S0960-894X(03)00017-9

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Starting from a 2-amino-6-methylpyridine PI group and following a strategy of enlarging it whilst reducing its polarity, we have developed a series of potent, moderately basic azaindoles which are intrinsically much more selective for thrombin versus trypsin. Certain pyrazinone acetamide azaindole derivatives have pharmacokinetic parameters after oral administration to dogs, or efficacy in vitro, comparable to an optimized pyrazinone acetamide 2-amino-6-methylpyridine derivative. (C) 2003 Elsevier Science Ltd. All rights reserved.

引用

页码：795 / 798

页数：4

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