Discovery of novel phenylpyridone derivatives as potent and selective MCH1R antagonists

Yuji Haga; Sayaka Mizutani; Akira Naya; Hiroyuki Kishino; Hisashi Iwaasa; Masahiko Ito; Junko Ito; Minoru Moriya; Nagaaki Sato; Norihiro Takenaga; Akane Ishihara; Shigeru Tokita; Akio Kanatani; Norikazu Ohtake

doi:10.1016/j.bmc.2010.12.002

Discovery of novel phenylpyridone derivatives as potent and selective MCH1R antagonists

Bioorg Med Chem. 2011 Jan 15;19(2):883-93. doi: 10.1016/j.bmc.2010.12.002. Epub 2010 Dec 6.

Authors

Yuji Haga¹, Sayaka Mizutani, Akira Naya, Hiroyuki Kishino, Hisashi Iwaasa, Masahiko Ito, Junko Ito, Minoru Moriya, Nagaaki Sato, Norihiro Takenaga, Akane Ishihara, Shigeru Tokita, Akio Kanatani, Norikazu Ohtake

Affiliation

¹ Tsukuba Research Institute, Banyu Pharmaceutical Co. Ltd, Japan.

PMID: 21190859
DOI: 10.1016/j.bmc.2010.12.002

Abstract

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.

MeSH terms

Animals
Drug Evaluation, Preclinical
Humans
Mice
Mice, Obese
Pyridones / chemical synthesis
Pyridones / chemistry*
Pyridones / pharmacokinetics
Rats
Receptors, Somatostatin / antagonists & inhibitors*
Receptors, Somatostatin / metabolism
Structure-Activity Relationship

Substances

4-((4-fluorobenzyl)oxy)-1-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)pyridin-2(1H)-one
Pyridones
Receptors, Somatostatin