Discovery of novel phenylpyridone derivatives as potent and selective MCH1R antagonists

The synthesis and evaluation of a series of phenylpyridone derivatives as MCH1R antagonists are described. The design, synthesis and structure–activity relationships of a novel class of N-phenylpyridone MCH1R antagonists are described. The core part of the N-phenylpyridone structure was newly design...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2011-01, Vol.19 (2), p.883-893
Main Authors: Haga, Yuji, Mizutani, Sayaka, Naya, Akira, Kishino, Hiroyuki, Iwaasa, Hisashi, Ito, Masahiko, Ito, Junko, Moriya, Minoru, Sato, Nagaaki, Takenaga, Norihiro, Ishihara, Akane, Tokita, Shigeru, Kanatani, Akio, Ohtake, Norikazu
Format: Article
Language:English
Subjects:
Animals
antagonists
Anti-obesity
Biological and medical sciences
Drug Evaluation, Preclinical
General and cellular metabolism. Vitamins
Hormones. Endocrine system
Humans
MCH1R antagonist
Medical sciences
Melanin-concentrating hormone
Mice
Mice, Obese
N-Phenylpyridone
Pharmacology. Drug treatments
Pyridones - chemical synthesis
Pyridones - chemistry
Pyridones - pharmacokinetics
Rats
Receptors, Somatostatin - antagonists & inhibitors
Receptors, Somatostatin - metabolism
Structure-Activity Relationship
structure-activity relationships
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The synthesis and evaluation of a series of phenylpyridone derivatives as MCH1R antagonists are described. The design, synthesis and structure–activity relationships of a novel class of N-phenylpyridone MCH1R antagonists are described. The core part of the N-phenylpyridone structure was newly designed and the side chain moieties that were attached to the core part were extensively explored. As a result of optimization of the N-phenylpyridone leads, we successfully developed the orally available, and brain-penetrable MCH1R selective antagonist 7c, exhibiting excellent anti-obese effect in diet-induced obese (DIO) mice.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2010.12.002