Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1362766 | Bioorganic & Medicinal Chemistry Letters | 2010 | 5 Pages |
Abstract
A novel series of trans-8-aminomethyl-1-oxa-3-azaspiro[4.5]decan-2-one derivatives was identified with potent NPY Y5 antagonist activity. Optimization of the original lead furnished compounds 23p and 23u, which combine sub-nanomolar Y5 activity with metabolic stability, oral bioavailability, brain penetration and strong preclinical profile for development. Both compounds significantly inhibited the food intake induced by a Y5 selective agonist with minimal effective doses of 3 mg/kg po.
Graphical abstractThe synthesis and SAR of a series of potent NPY Y5 antagonists is reported. Optimization led to the identification of compounds 23p and 23u (fpKi = 10.0).Figure optionsDownload full-size imageDownload as PowerPoint slide
Related Topics
Physical Sciences and Engineering
Chemistry
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Authors
Colin P. Leslie, Jonathan Bentley, Matteo Biagetti, Stefania Contini, Romano Di Fabio, Daniele Donati, Thorsten Genski, Sebastien Guery, Angelica Mazzali, Giancarlo Merlo, Domenica A. Pizzi, Fabiola Sacco, Catia Seri, Michela Tessari, Laura Zonzini,