title: Optimization of benzimidazole series as opioid receptor-like 1 (ORL1) antagonists: SAR study directed toward improvement of selectivity over hERG activity.
abstract: A structure-activity relationship (SAR) study on the benzimidazole series of opioid receptor-like 1 (ORL1) antagonists related to 1 is described. Optimization of 1 by introduction of a hydrophilic substituent into the thioether part resulted in identification of potent ORL1 antagonists with high selectivity over binding affinity for hERG and other opioid receptors.
authors.affiliation: Tsukuba Research Institute, Banyu Pharmaceutical Co, Ltd, Tsukuba, Ibaraki, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kato
authors.forename: Izumi
authors.initials: I
authors.lastname: Yamamoto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shimizu
authors.forename: Sayaka
authors.initials: S
authors.lastname: Mizutani
authors.forename: Masanori
authors.initials: M
authors.lastname: Asai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawamoto
authors.forename: Satoru
authors.initials: S
authors.lastname: Ito
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshizumi
authors.forename: Mioko
authors.initials: M
authors.lastname: Hirayama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ozaki
authors.forename: Hisashi
authors.initials: H
authors.lastname: Ohta
authors.forename: Osamu
authors.initials: O
authors.lastname: Okamoto
mesh_terms: D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D003510:Cyclohexanes / Q000138:chemical synthesis* / Q000494:pharmacology; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000378:metabolism*; D009292:Narcotic Antagonists; D011957:Receptors, Opioid / Q000378:metabolism; D013329:Structure-Activity Relationship; D000094942:Nociceptin Receptor
chemical_list: D001562:Benzimidazoles; D003510:Cyclohexanes; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor