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

Lingyun Wu; Kai Lu; Mathivanan Packiarajan; Vrej Jubian; Gamini Chandrasena; Toni C Wolinsky; Mary W Walker

doi:10.1016/j.bmcl.2012.01.117

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

Bioorg Med Chem Lett. 2012 Mar 15;22(6):2167-71. doi: 10.1016/j.bmcl.2012.01.117. Epub 2012 Feb 4.

Authors

Lingyun Wu¹, Kai Lu, Mathivanan Packiarajan, Vrej Jubian, Gamini Chandrasena, Toni C Wolinsky, Mary W Walker

Affiliation

¹ Chemical & Pharmacokinetic Sciences, Paramus, NJ 07652, USA. wuly2000@yahoo.com

PMID: 22361135
DOI: 10.1016/j.bmcl.2012.01.117

Abstract

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 0.1 mg/kg. The indolyl glycinamide 12c also inhibits NPY5 agonist induced feeding at a dose of 1 mg/kg. Both compounds 10a and 12c represent potential tools for further investigation into the biology of the NPY5 receptor.

MeSH terms

Amides / chemical synthesis*
Amides / pharmacokinetics
Amides / pharmacology
Animals
Appetite Stimulants / chemical synthesis
Appetite Stimulants / pharmacokinetics
Appetite Stimulants / pharmacology
Brain / drug effects
Cell Line
Eating / drug effects
Glycine / analogs & derivatives*
Glycine / chemical synthesis*
Glycine / pharmacokinetics
Glycine / pharmacology
Humans
Indoles / chemical synthesis*
Indoles / pharmacokinetics
Indoles / pharmacology
Kinetics
Male
Molecular Structure
Permeability
Rats
Rats, Sprague-Dawley
Receptors, Neuropeptide Y / agonists
Receptors, Neuropeptide Y / antagonists & inhibitors*
Receptors, Neuropeptide Y / chemistry
Structure-Activity Relationship

Substances

Amides
Appetite Stimulants
Indoles
Receptors, Neuropeptide Y
neuropeptide Y5 receptor
Glycine