Novel bis-arylsulfonamides and aryl sulfonimides as inactivators of plasminogen activator inhibitor-1 (PAI-1)

被引：9

作者：

El-Ayache, Nadine C. ^{[1
]}

Li, Shih-Hon ^{[2
]}

Warnock, Mark ^{[2
]}

Lawrence, Daniel A. ^{[2
]}

Emal, Cory D. ^{[1
]}

机构：

[1] Eastern Michigan Univ, Dept Chem, Ypsilanti, MI 48197 USA

[2] Univ Michigan, Sch Med, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 03期

关键词：

PAI-1; inhibitors; Bis-arylsulfonamide; Aryl sulfonimide; MECHANISM; THROMBOSIS; TYPE-1; ANGIOGENESIS; TIPLAXTININ; DERIVATIVES; MIGRATION; MODEL; MICE;

D O I：

10.1016/j.bmcl.2009.12.051

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Inactivators of plasminogen activator inhibitor-1 (PAI-1) have been identified as possible treatments for a range of conditions, including atherosclerosis, venous thrombosis, and obesity. We describe the synthesis and inhibitory activity of a novel series of compounds based on bis-arylsulfonamide and aryl sulfonimide motifs that show potent and specific activity towards PAI-1. Inhibitors containing short linking units between the sulfonyl moieties and a 3,4-dihydroxy aryl substitution pattern showed the most potent inhibitory activity, and retained high specificity for PAI-1 over the structurally-related serpin anti-thrombin III (ATIII). (c) 2009 Elsevier Ltd. All rights reserved.

引用

页码：966 / 970

页数：5

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