title: Discovery of novel phenylpyridone derivatives as potent and selective MCH1R antagonists.
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.
authors.affiliation: Tsukuba Research Institute, Banyu Pharmaceutical Co. Ltd, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Haga
authors.forename: Sayaka
authors.initials: S
authors.lastname: Mizutani
authors.forename: Akira
authors.initials: A
authors.lastname: Naya
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kishino
authors.forename: Hisashi
authors.initials: H
authors.lastname: Iwaasa
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ito
authors.forename: Junko
authors.initials: J
authors.lastname: Ito
authors.forename: Minoru
authors.initials: M
authors.lastname: Moriya
authors.forename: Nagaaki
authors.initials: N
authors.lastname: Sato
authors.forename: Norihiro
authors.initials: N
authors.lastname: Takenaga
authors.forename: Akane
authors.initials: A
authors.lastname: Ishihara
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tokita
authors.forename: Akio
authors.initials: A
authors.lastname: Kanatani
authors.forename: Norikazu
authors.initials: N
authors.lastname: Ohtake
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical; D006801:Humans; D051379:Mice; D008820:Mice, Obese; D011728:Pyridones / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C557920:4-((4-fluorobenzyl)oxy)-1-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)pyridin-2(1H)-one; D011728:Pyridones; D017481:Receptors, Somatostatin