Synthesis and biologic evaluation of selective inhibitors of 11β-HSD1 as a potential treatment for metabolic disorders

MEDI 53

Santhosh F. Neelamkavil, santhosh.neelamkavil@spcorp.com1, Craig D. Boyle, craig.boyle@spcorp.com1, Samuel Chackalamannil1, Hana Baker2, Timothy Kowalski3, Lili Zhang4, and Giuseppe Terracina4. (1) Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, K-15-2-2545, Kenilworth, NJ 07033, (2) CV/Metabolic Diseases Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033-0539, (3) Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033-0539, (4) Neurobiology, Schering-Plough Research Institute, 2015 Galloping Hill Rd, Kenilworth, NJ 07033
11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is an enzyme that activates the glucocorticoid receptor by converting inactive cortisone to active cortisol. In contrast, 11β-HSD2 catalyzes the inactivation of active glucocorticoid. Genetic deletion of 11β-HSD1 lowers plasma glucose levels in mice fed on high-fat diets and attenuates the activation of enzymes involved in hepatic gluconeogenesis suggesting that inhibitors of this enzyme may be of therapeutic use in various metabolic disorders. This presentation will discuss our discovery of several potent and selective compounds as inhibitors of 11β-HSD1.
 

Poster Session
7:00 PM-9:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Medicinal Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007