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Get Free AccessWe report the discovery of potent benzamide inhibitors of 11beta-hydroxysteroid dehydrogenase (11beta-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 11beta-HSD1 activity in a monkey ex vivo pharmacodynamic model.
Lisa D. Julian, Zhong Lin Wang, Tracy Bostick, Seb Caille, Rebekah Choi, Michael DeGraffenreid, Yongmei Di, Xiaodong He, Randall W. Hungate, Juan C. Jaén, Jinsong Liu, Mario Monshouwer, Dustin L. McMinn, Yosup Rew, Athena Sudom, Daqing Sun, Hua Tu, Stefania Ursu, Nigel P.C. Walker, Xuelei Yan, Qiuping Ye, Jay P. Powers (2008). Discovery of Novel, Potent Benzamide Inhibitors of 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1) Exhibiting Oral Activity in an Enzyme Inhibition ex Vivo Model<sup>▽</sup>. , 51(13), DOI: https://doi.org/10.1021/jm800310g.
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Type
Article
Year
2008
Authors
22
Datasets
0
Total Files
0
Language
en
DOI
https://doi.org/10.1021/jm800310g
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