| Literature DB >> 17919905 |
Chester Yuan1, David J St Jean, Qingyian Liu, Lynn Cai, Aiwen Li, Nianhe Han, George Moniz, Ben Askew, Randall W Hungate, Lars Johansson, Lars Tedenborg, David Pyring, Meredith Williams, Clarence Hale, Michelle Chen, Rod Cupples, Jiandong Zhang, Steven Jordan, Michael D Bartberger, Yaxiong Sun, Maurice Emery, Minghan Wang, Christopher Fotsch.
Abstract
A series of 2-anilinothiazolones were prepared as inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). The most potent compounds contained a 2-chloro or 2-fluoro group on the aniline ring with an isopropyl substituent on the 5-position of the thiazolone ring (compounds 2 and 3, respectively). The binding mode was determined through the X-ray co-crystal structure of the enzyme with compound 3. This compound was also approximately 70-fold selective over 11beta-HSD2 and was orally bioavailable in rat pharmacokinetic studies. However, compound 3 was >580-fold less active in the 11beta-HSD1 cell assay when tested in the presence of 3% human serum albumin.Entities:
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Year: 2007 PMID： 17919905 DOI： 10.1016/j.bmcl.2007.09.070
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823