Discovery and SAR of novel derivatives as 11β-hydroxysteroid dehydrogenase type 1 inhibitors

MEDI 52

Claire M. Lankin, claire.lankin@spcorp.com1, Craig D. Boyle, craig.boyle@spcorp.com1, Samuel Chackalamannil1, Unmesh Shah, unmesh.shah@spcorp.com1, Hana Baker2, Timothy Kowalski3, Lili Zhang4, and Giuseppe Terracina4. (1) Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, 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 converts inactive cortisone to cortisol in tissues such as liver and fat, increasing the local concentrations of active glucocorticoid. Data suggests that excess local glucocorticoid may be involved in the development of abdominal obesity and metabolic syndrome. Therefore, the inhibition of 11β-HSD1 may represent a potential treatment for diabetes and metabolic syndrome by suppressing the regeneration of active cortisol and regulating glucocorticoid action.

The synthesis, structure activity relationship and biological activity of these derivatives as inhibitors of 11β-HSD1 will be described.

 

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