Bioorg Med Chem Lett. 2010 Feb 1;20(3):966-70. Epub 2009 Dec 21.

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

El-Ayache NC, Li SH, Warnock M, Lawrence DA, Emal CD.

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Department of Chemistry, Eastern Michigan University, 225 Mark Jefferson, Ypsilanti, MI 48197, United States.

Abstract

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).

PMID:: 20056540; [PubMed - indexed for MEDLINE]
PMCID: PMC2957478

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