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J Med Chem. 2007 Feb 8;50(3):429-32.

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

Author information

1
Department of Medicinal Chemistry, Amgen, Inc., One Amgen Center Drive, Thousand Oaks, California 91320-1799, USA. david.st.jean@amgen.com

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.

PMID:
17266194
DOI:
10.1021/jm061214f
[Indexed for MEDLINE]

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