Syntheses and SAR of piperidin-3-yl ureas as potent and selective 11β-HSD-1 inhibitors

MEDI 54

Yun-Long Li, yunli@incyte.com1, Lori Bostrom1, Jincong Zhuo, jzhuo@incyte.com1, Yanlong Li1, Maryanne Covington2, Reid Huber1, Brian Metcalf1, and Wenqing Yao, WYao@incyte.com1. (1) Incyte Corporation, Experimental Station E336, Route 141 & Henry Clay Road, Wilmington, DE 19880, (2) Bristol-Myers Squibb Company
The enzyme 11β-hydroxysteroid dehydrogenase type 1, or 11β-HSD-1, catalyzes the intracellular conversion of functionally inert cortisone to active cortisol. Cortisol elevates blood glucose levels by increasing glucose production in the liver and by inhibiting the uptake and disposal of glucose in muscle and adipose tissue, essentially acting as an antagonist of insulin. 11β-HSD-1 inhibitors may abrogate cortisol's antagonistic actions toward insulin and thus offer a new approach to treating type 2 diabetes and allied conditions such as dyslipidemia, atherosclerosis, and coronary heart disease. Herein we report the design, syntheses and SAR of novel 3-aminopiperidinyl based ureas as potent and selective 11β-HSD-1 inhibitors.

                                                                                         

 

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