title: Identification of a novel and orally available benzimidazole derivative as an NPY Y5 receptor antagonist with in vivo efficacy.
abstract: Optimization of lead compound 2 is described, mainly focusing on modification at the C-2 position of the benzimidazole core. Replacement of the phenyl linker of 2 with saturated rings resulted in identification of compound 8b which combines high Y5 receptor binding affinity with a good ADME profile leading to in vivo efficacy.
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: Naoki
authors.initials: N
authors.lastname: Omori
authors.forename: Naoki
authors.initials: N
authors.lastname: Kouyama
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nishiura
authors.forename: Kyouhei
authors.initials: K
authors.lastname: Hayashi
authors.forename: Kana
authors.initials: K
authors.lastname: Watanabe
authors.forename: Yukari
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Chiba
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; D001562:Benzimidazoles / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D004355:Drug Stability; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008820:Mice, Obese; D011485:Protein Binding / Q000187:drug effects; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors*; D012995:Solubility; D013329:Structure-Activity Relationship
chemical_list: D001562:Benzimidazoles; D017476:Receptors, Neuropeptide Y; C100568:neuropeptide Y5 receptor