Discovery of Novel, Potent Benzamide Inhibitors of 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1) Exhibiting Oral Activity in an Enzyme Inhibition ex Vivo …

…, J Liu, M Monshouwer, D McMinn, Y Rew…

Index: Julian, Lisa D.; Wang, Zhulun; Bostick, Tracy; Caille, Seb; Choi, Rebekah; DeGraffenreid, Michael; Di, Yongmei; He, Xiao; Hungate, Randall W.; Jaen, Juan C.; Liu, Jinsong; Monshouwer, Mario; McMinn, Dustin; Rew, Yosup; Sudom, Athena; Sun, Daqing; Tu, Hua; Ursu, Stefania; Walker, Nigel; Yan, Xuelei; Ye, Qiuping; Powers, Jay P. Journal of Medicinal Chemistry, 2008 , vol. 51, # 13 p. 3953 - 3960

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Citation Number: 41

Abstract

We report the discovery of potent benzamide inhibitors of 11β-hydroxysteroid dehydrogenase (11β-HSD1). The optimization and correlation of in vitro and in vivo metabolic stability will be described. Through modifications to our initial lead 2, we discovered pyridyl compound 13. This compound has a favorable pharmacokinetic profile across three species and showed a dose-dependent decrease in adipose 11β-HSD1 ...