959974-33-5Relevant academic research and scientific papers
The discovery of 2-anilinothiazolones as 11β-HSD1 inhibitors
Yuan, Chester,St. Jean Jr., David J.,Liu, Qingyian,Cai, Lynn,Li, Aiwen,Han, Nianhe,Moniz, George,Askew, Ben,Hungate, Randall W.,Johansson, Lars,Tedenborg, Lars,Pyring, David,Williams, Meredith,Hale, Clarence,Chen, Michelle,Cupples, Rod,Zhang, Jiandong,Jordan, Steven,Bartberger, Michael D.,Sun, Yaxiong,Emery, Maurice,Wang, Minghan,Fotsch, Christopher
, p. 6056 - 6061 (2008/09/16)
A series of 2-anilinothiazolones were prepared as inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-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 ～70-fold selective over 11β-HSD2 and was orally bioavailable in rat pharmacokinetic studies. However, compound 3 was >580-fold less active in the 11β-HSD1 cell assay when tested in the presence of 3% human serum albumin.
