Synthesis and in vitro evaluation of a series of diketopiperazine inhibitors of plasminogen activator inhibitor-1

• Published in: Bioorganic & medicinal chemistry letters Vol. 11; no. 19; pp. 2589 - 2592
• Main Authors: Folkes, Adrian, Roe, Michael B, Sohal, Sukhjit, Golec, Julian, Faint, Richard, Brooks, Teresa, Charlton, Peter
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 08.10.2001; Elsevier
• Subjects: Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Diketopiperazines; Medical sciences; Pharmacology. Drug treatments; Piperazines - chemical synthesis; Piperazines - chemistry; Piperazines - pharmacology; Plasminogen Activator Inhibitor 1 - metabolism; Structure-Activity Relationship; Five membered ring; Nitrogen heterocycle; Lactam; In vitro; Plasminogen activator inhibitor 1; Thiophene derivatives; Sulfur heterocycle; Structure activity relation; Carboxylic acid; Carboxamide; Benzenic compound; Piperazine derivatives; Chemical synthesis; Fibrinolytic
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(01)00508-X

We have synthesized and evaluated a series of diketopiperazine-based inhibitors of PAI-1. These studies resulted in the identification of 34 which inhibited PAI-1 in vitro with an IC 50=0.2 μM. The synthesis and SAR of these compounds are described. We have synthesized and evaluated a series of diketopiperazine-based inhibitors of PAI-1. These studies resulted in the identification of 34 which inhibited PAI-1 in vitro with an IC 50=0.2 μM. The synthesis and SAR of these compounds are described.