title: Identification of novel benzimidazole series of potent and selective ORL1 antagonists.
abstract: Structure-activity studies on benzimidazole lead 1 obtained from library screening led to the discovery of potent and selective ORL1 antagonist 28, 5-chloro-2-[(1-ethyl-1-methylpropyl)thio]-6-[4-(2-hydroxyethyl)piperazin-1-yl]-1H-benzimidazole, which is structurally distinct from conventional non-peptide antagonists known to date.
authors.affiliation: Banyu Tsukuba Research Institute, Banyu Pharmaceutical Co. Ltd., Okubo-3, Tsukuba, Ibaraki 300-2611, Japan. osamu_okamoto@merck.com
authors.forename: Osamu
authors.initials: O
authors.lastname: Okamoto
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawamoto
authors.forename: Satoru
authors.initials: S
authors.lastname: Ito
authors.forename: Atsushi
authors.initials: A
authors.lastname: Satoh
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kato
authors.forename: Izumi
authors.initials: I
authors.lastname: Yamamoto
authors.forename: Sayaka
authors.initials: S
authors.lastname: Mizutani
authors.forename: Masaya
authors.initials: M
authors.lastname: Hashimoto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shimizu
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sakoh
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nagatomi
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Iwasawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ishii
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ozaki
authors.forename: Hisashi
authors.initials: H
authors.lastname: Ohta
mesh_terms: D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D015394:Molecular Structure; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D013329:Structure-Activity Relationship; D000094942:Nociceptin Receptor
chemical_list: C529700:5-chloro-2-((1-ethyl-1-methylpropyl)thio)-6-(4-(2-hydroxyethyl)piperazin-1-yl)-1H-benzimidazole; D001562:Benzimidazoles; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; C000722283:OPRL1 protein, human