title: Identification of 2-aminobenzimidazoles as potent melanin-concentrating hormone 1-receptor (MCH1R) antagonists.
abstract: A series of 2-aminobenzimidazole-based MCH1R antagonists was identified by core replacement of the aminoquinoline lead 1. Subsequent modification of the 2- and 5-positions led to improvement in potency and intrinsic clearance. Compound 25 exhibited good plasma and brain exposure, and attenuated MCH induced food intake at 30mg/kg PO in rats.
authors.affiliation: Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd, Okubo-3, Tsukuba, Ibaraki 300-2611, Japan. minoru_moriya@merck.com
authors.forename: Minoru
authors.initials: M
authors.lastname: Moriya
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kishino
authors.forename: Shunji
authors.initials: S
authors.lastname: Sakuraba
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Takuya
authors.initials: T
authors.lastname: Suga
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Takahashi
authors.forename: Takao
authors.initials: T
authors.lastname: Suzuki
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ito
authors.forename: Junko
authors.initials: J
authors.lastname: Ito
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Moriya
authors.forename: Norihiro
authors.initials: N
authors.lastname: Takenaga
authors.forename: Hisashi
authors.initials: H
authors.lastname: Iwaasa
authors.forename: Akane
authors.initials: A
authors.lastname: Ishihara
authors.forename: Akio
authors.initials: A
authors.lastname: Kanatani
authors.forename: Takehiro
authors.initials: T
authors.lastname: Fukami
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D004435:Eating / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D019440:Anti-Obesity Agents; D001562:Benzimidazoles; C491208:MCHR1 protein, rat; D017481:Receptors, Somatostatin; C027391:2-aminobenzimidazole