Discovery of potent, selective sulfonylfuran urea endothelial lipase inhibitors

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

文献索引：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

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被引用次数: 34

摘要

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 ...