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J Med Chem. 2008 Jul 10;51(13):3953-60. doi: 10.1021/jm800310g. Epub 2008 Jun 14.

Discovery of novel, potent benzamide inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) exhibiting oral activity in an enzyme inhibition ex vivo model.

Author information

1
Amgen, Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, USA. ljulian@amgen.com

Abstract

We 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.

PMID:
18553955
DOI:
10.1021/jm800310g
[Indexed for MEDLINE]

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