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Design, synthesis and SAR of a novel series of benzimidazoles as potent NPY Y5 antagonists.

Authors :
Pizzi DA
Leslie CP
Mazzali A
Seri C
Biagetti M
Bentley J
Genski T
Di Fabio R
Contini S
Sabbatini FM
Zonzini L
Caberlotto L
Source :
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2010 Dec 01; Vol. 20 (23), pp. 7120-3. Date of Electronic Publication: 2010 Sep 17.
Publication Year :
2010

Abstract

A novel class of benzimidazole NPY Y5 receptor antagonists was prepared exploiting a privileged spirocarbamate moiety. The structure-activity relationship of this series and efforts to achieve a profile suitable for further development and an appropriate pharmacokinetic profile in rat are described. Optimisation led to the identification of the brain penetrant, orally bioavailable Y5 antagonist 9b which significantly inhibited the food intake induced by a Y5 selective agonist with a minimal effective dose of 30mg/kg po.<br /> (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Details

Language :
English
ISSN :
1464-3405
Volume :
20
Issue :
23
Database :
MEDLINE
Journal :
Bioorganic & medicinal chemistry letters
Publication Type :
Academic Journal
Accession number :
20951033
Full Text :
https://doi.org/10.1016/j.bmcl.2010.09.064