Novel bis-arylsulfonamides and aryl sulfonimides as inactivators of plasminogen activator inhibitor-1 (PAI-1).
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).
El-Ayache
Nadine C
NC
Department of Chemistry, Eastern Michigan University, 225 Mark Jefferson, Ypsilanti, MI 48197, United States.
Li
Shih-Hon
SH
Warnock
Mark
M
Lawrence
Daniel A
DA
Emal
Cory D
CD
D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D015849:Plasminogen Inactivators / Q000737:chemistry* / Q000378:metabolism*; D013449:Sulfonamides / Q000737:chemistry* / Q000378:metabolism*
D017395:Plasminogen Activator Inhibitor 1; D015849:Plasminogen Inactivators; D013449:Sulfonamides