2. Academic Validation
  3. 2-(S)-phenethylaminothiazolones as potent, orally efficacious inhibitors of 11beta-hydroxysteriod dehydrogenase type 1

2-(S)-phenethylaminothiazolones as potent, orally efficacious inhibitors of 11beta-hydroxysteriod dehydrogenase type 1

  • J Med Chem. 2007 Feb 8;50(3):429-32. doi: 10.1021/jm061214f.
David J St Jean Jr 1,  Chester Yuan,  Eric A Bercot,  Rod Cupples,  Michelle Chen,  Jenne Fretland,  Clarence Hale,  Randall W Hungate,  Renee Komorowski,  Murielle Veniant,  Minghan Wang,  Xiping Zhang,  Christopher Fotsch
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Amgen, Inc., One Amgen Center Drive, Thousand Oaks, California 91320-1799, USA. david.st.jean@amgen.com
PMID: 17266194 DOI: 10.1021/jm061214f
Abstract

11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is the enzyme that converts cortisone to cortisol. A growing body of evidence suggests that selective inhibition of 11beta-HSD1 could potentially treat metabolic syndrome as well as type 2 diabetes. Through modification of our initial lead 1, we have discovered trifluoromethyl thiazolone 17. This compound had a Ki of 22 nM, possessed low in vivo clearance, and showed a 91% inhibition of adipose 11beta-HSD1 enzymatic activity in a mouse ex vivo pharmacodynamic model.

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