Novel bis-arylsulfonamides and aryl sulfonimides as inactivators of plasminogen activator inhibitor-1 (PAI-1).
Bioorganic & medicinal chemistry letters 2009 Dec 21; In press
El-Ayache N NC, Li S SH, Warnock M, Lawrence D DA, Emal C CD
Department of Chemistry, Eastern Michigan University, 225 Mark Jefferson, Ypsilanti, MI 48197, United States.
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).
Keywords: plasminogen activator inhibitor-1 PAI-1 atherosclerosis venous thrombosis obesity