Novel benzoxazole inhibitors of mPGES-1

…, J Shao, D Demian, K Hoffmaster, F Berlioz…

文献索引：Kablaoui, Natasha; Patel, Snahel; Shao, Jay; Demian, Douglas; Hoffmaster, Keith; Berlioz, Francioise; Vazquez, Michael L.; Moore, William M.; Nugent, Richard A. Bioorganic and Medicinal Chemistry Letters, 2013 , vol. 23, # 3 p. 907 - 911

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被引用次数: 9

摘要

A novel series of potent benzoxazole mPGES-1 inhibitors has been derived from a hit from a high throughput screen. Compound 37 displays mPGES-1 inhibition in an enzyme assay (0.018 μM) and PGE-2 inhibition in a cell-based assay (0.034 μM). It demonstrates 500-and 2500-fold selectivity for mPGES-1 over COX-2 and 6-keto PGF-1α, respectively. In vivo PK studies in dogs demonstrate 55% oral bioavailability and an 7h half-life.