Discovery of potent, selective sulfonylfuran urea endothelial lipase inhibitors

…, MA Cichy-Knight, SE Dowdell, AK Dunn, D Lee…

Index: Goodman, Krista B.; Bury, Michael J.; Cheung, Mui; Cichy-Knight, Maria A.; Dowdell, Sarah E.; Dunn, Allison K.; Lee, Dennis; Lieby, Jeffrey A.; Moore, Michael L.; Scherzer, Daryl A.; Sha, Deyou; Suarez, Dominic P.; Murphy, Dennis J.; Harpel, Mark R.; Manas, Eric S.; McNulty, Dean E.; Annan, Roland S.; Matico, Rosalie E.; Schwartz, Benjamin K.; Trill, John J.; Sweitzer, Thomas D.; Wang, Da-yuan; Keller, Paul M.; Krawiec, John A.; Jaye, Michael C. Bioorganic and Medicinal Chemistry Letters, 2009 , vol. 19, # 1 p. 27 - 30

Full Text: HTML

Citation Number: 34

Abstract

Endothelial lipase (EL) activity has been implicated in HDL catabolism, vascular inflammation, and atherogenesis, and inhibitors are therefore expected to be useful for the treatment of cardiovascular disease. Sulfonylfuran urea 1 was identified in a high-throughput screening campaign as a potent and non-selective EL inhibitor. A lead optimization effort was undertaken to improve potency and selectivity, and modifications leading to improved ...