title: Identification of a novel benzimidazole derivative as a highly potent NPY Y5 receptor antagonist with an anti-obesity profile.
abstract: Optimization of HTS hit 1 for NPY Y5 receptor binding affinity, CYP450 inhibition, solubility and metabolic stability led to the identification of some orally available oxygen-linker derivatives for in vivo study. Among them, derivative 4i inhibited food intake induced by the NPY Y5 selective agonist, and chronic oral administration of 4i in DIO mice caused a dose-dependent reduction of body weight gain.
authors.affiliation: Medicinal Research Laboratories, Shionogi & Co., Ltd, 1-1, Futabacho 3-chome, Toyonaka, Osaka 561-0825, Japan. yuusuke.tamura@shionogi.co.jp
authors.forename: Yuusuke
authors.initials: Y
authors.lastname: Tamura
authors.forename: Kyouhei
authors.initials: K
authors.lastname: Hayashi
authors.forename: Naoki
authors.initials: N
authors.lastname: Omori
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nishiura
authors.forename: Kana
authors.initials: K
authors.lastname: Watanabe
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Tanaka
authors.forename: Masahiko
authors.initials: M
authors.lastname: Fujioka
authors.forename: Naoki
authors.initials: N
authors.lastname: Kouyama
authors.forename: Akira
authors.initials: A
authors.lastname: Yukimasa
authors.forename: Yukari
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Chiba
authors.forename: Hideki
authors.initials: H
authors.lastname: Tanioka
authors.forename: Hirohide
authors.initials: H
authors.lastname: Nambu
authors.forename: Hideo
authors.initials: H
authors.lastname: Yukioka
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sato
authors.forename: Takayuki
authors.initials: T
authors.lastname: Okuno
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019440:Anti-Obesity Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001562:Benzimidazoles / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006207:Half-Life; D051379:Mice; D009765:Obesity / Q000188:drug therapy; D051381:Rats; D017476:Receptors, Neuropeptide Y / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D015430:Weight Gain / Q000187:drug effects
chemical_list: D019440:Anti-Obesity Agents; D001562:Benzimidazoles; D065607:Cytochrome P-450 Enzyme Inhibitors; D017476:Receptors, Neuropeptide Y; D013450:Sulfones; C100568:neuropeptide Y5 receptor; D003577:Cytochrome P-450 Enzyme System; C031000:benzimidazole