New fibrinolytic agents: benzothiophene derivatives as inhibitors of the t-PA-PAI-1 complex formation.
The synthesis and activity of novel benzothiophene derivatives are described. In the t-Pa-induced fibrin clot lysis assay, several compounds inhibit the formation of the tPa-PAI-1 complex with submicromolar IC(50). This class of compounds potentially represents a new generation of antithrombotic-fibrinolytic agents.
De Nanteuil
Guillaume
G
Division D of Medicinal Chemistry, Institut de Recherches Servier, 11 rue des Moulineaux, 92150 Suresnes, France. guillaume.denanteuil@fr.netgrs.com
Lila-Ambroise
Christine
C
Rupin
Alain
A
Vallez
Marie-Odile
MO
Verbeuren
Tony J
TJ
D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000494:pharmacology*; D010959:Tissue Plasminogen Activator / Q000037:antagonists & inhibitors* / Q000378:metabolism
D005343:Fibrinolytic Agents; D017395:Plasminogen Activator Inhibitor 1; D013876:Thiophenes; C088015:benzothiophene; D010959:Tissue Plasminogen Activator