The design and synthesis of a tricyclic single-nitrogen scaffold that serves as a 5-HT sub(2C) receptor agonist

5-HT sub(2C) agonists have shown efficacy in limiting food consumption and thus may serve as an important drug class in combating obesity. We describe the design and synthesis of a novel tricyclic single-nitrogen scaffold that was used to produce 5-HT sub(2C) agonists. SAR was developed around this...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2006-01, Vol.16 (15), p.4130-4134
Main Authors: Huck, Bayard R, Llamas, Luis, Robarge, Michael J, Dent, Thomas C, Song, Jianping, Hodnick, William F, Crumrine, Chris, Stricker-Krongrad, Alain, Harrington, John, Brunden, Kurt R, Bennani, Youssef L
Format: Article
Language:English
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Summary:5-HT sub(2C) agonists have shown efficacy in limiting food consumption and thus may serve as an important drug class in combating obesity. We describe the design and synthesis of a novel tricyclic single-nitrogen scaffold that was used to produce 5-HT sub(2C) agonists. SAR was developed around this chemotype and compounds were identified that were potent (K sub(i) - 15 nM) and selective relative to other 5-HT sub(2) receptors. The most promising compound displayed a good pharmacokinetic profile in multiple animal species, and was efficacious in an acute feeding study in rats.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2006.04.070