Discovery and synthesis of nipecotic amide as novel, potent and selective 11ß-HSD-1 inhibitors

MEDI 48

Jincong Zhuo, jzhuo@incyte.com1, Meizhong Xu1, Colin Zhang1, Dingquan Qian1, Yanlong Li1, Reid Huber1, Maryanne Covington2, Cindy Marando1, Brian Metcalf1, and Wenqing Yao, WYao@incyte.com1. (1) Incyte Corporation, Experimental Station - E336/208B, Route 141 & Herry Clay Road, Wilmington, DE 19880, (2) Bristol-Myers Squibb Company
11ß-HSD-1 (11ß-hydroxysteroid dehydrogenase type I) is an enzyme that belongs to the short-chain dehydrogenase superfamily. It is highly expressed in liver and adipose tissues. 11ß-HSD-1 catalyzes the inter-conversion of inactive cortisone to active cortisol. 11ß-HSD-1 knock out mice show improved lipid profiles and hepatic insulin sensitivity. Therefore, 11ß-HSD-1 inhibitors have been of great interest as a therapeutic intervention for symptoms of metabolic syndrome including visceral adiposity, hyperglycemia. We will discuss the discovery and SAR of a novel series of nipecotic amides as potent and selective 11ß-HSD-1 inhibitors.

 

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

Sci-Mix
8:00 PM-10:00 PM, Monday, August 20, 2007 BCEC -- Exhibit Hall - B2, Sci-Mix

Division of Medicinal Chemistry

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