Indolyl and dihydroindolyl N-glycinamides as potent and in vivo active NPY5 antagonists

A novel series of indolyl and dihydroindolyl glycinamides were identified as potent NPY5 antagonists with in vivo activity from screen hit 1. The dihydroindolyl glycinamide 10a significantly inhibits NPY5 agonist induced feeding at a dose of 0.1mg/kg. The indolyl glycinamide 12c also inhibits NPY5 a...

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Bibliographic Details
Published in:	Bioorganic & medicinal chemistry letters Vol. 22; no. 6; pp. 2167 - 2171
Main Authors:	Wu, Lingyun, Lu, Kai, Packiarajan, Mathivanan, Jubian, Vrej, Chandrasena, Gamini, Wolinsky, Toni C., Walker, Mary W.
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier Ltd 15-03-2012 Elsevier
Subjects:	agonists Amides - chemical synthesis Amides - pharmacokinetics Amides - pharmacology Animals antagonists Appetite Stimulants - chemical synthesis Appetite Stimulants - pharmacokinetics Appetite Stimulants - pharmacology Biological and medical sciences Biological Sciences Brain - drug effects Brain penetration Cell Line chemistry Dihydroindolyl glycinamide Eating - drug effects Glycine - analogs & derivatives Glycine - chemical synthesis Glycine - pharmacokinetics Glycine - pharmacology Humans Indoles - chemical synthesis Indoles - pharmacokinetics Indoles - pharmacology Indolyl glycinamide Kinetics Male Medical sciences Molecular Structure Permeability PGP efflux Pharmacology. Drug treatments Rats Rats, Sprague-Dawley Receptors, Neuropeptide Y - agonists Receptors, Neuropeptide Y - antagonists & inhibitors Receptors, Neuropeptide Y - chemistry Structure-Activity Relationship Indolyl glycinamide Brain penetration PGP efflux Dihydroindolyl glycinamide Rat Rodentia Chemical structure Blood brain barrier In vivo Vertebrata Mammalia Animal Antagonist Pharmacokinetics Indole derivatives Benzothiazine derivatives
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Summary:	A novel series of indolyl and dihydroindolyl glycinamides were identified as potent NPY5 antagonists with in vivo activity from screen hit 1. The dihydroindolyl glycinamide 10a significantly inhibits NPY5 agonist induced feeding at a dose of 0.1mg/kg. The indolyl glycinamide 12c also inhibits NPY5 agonist induced feeding at a dose of 1mg/kg. Both compounds 10a and 12c represent potential tools for further investigation into the biology of the NPY5 receptor.
Bibliography:	http://dx.doi.org/10.1016/j.bmcl.2012.01.117 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2012.01.117