title: Identification of a novel spiropiperidine opioid receptor-like 1 antagonist class by a focused library approach featuring 3D-pharmacophore similarity.
abstract: A focused library approach identifying novel leads to develop a potent ORL1 antagonist is described. Beginning from a compound identified by random screening, an exploratory library that exhibited a diverse display of pharmacophores was designed. After evaluating ORL1 antagonistic activity, a highly focused library was designed based on 3D-pharmacophore similarity to known actives. A novel D-proline amide class was identified in this library and was found to possess potent ORL1 antagonistic activity.
authors.affiliation: Banyu Tsukuba Research Institute, Banyu Pharmaceutical Co. Ltd., Okubo 3, Tsukuba 300-2611, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Goto
authors.forename: Sachie
authors.initials: S
authors.lastname: Arai-Otsuki
authors.forename: Yukari
authors.initials: Y
authors.lastname: Tachibana
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ichikawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ozaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Iwasawa
authors.forename: Osamu
authors.initials: O
authors.lastname: Okamoto
authors.forename: Shoki
authors.initials: S
authors.lastname: Okuda
authors.forename: Hisashi
authors.initials: H
authors.lastname: Ohta
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sagara
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D020650:Combinatorial Chemistry Techniques; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D015394:Molecular Structure; D009292:Narcotic Antagonists; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry; D011392:Proline / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D011869:Radioligand Assay; D011957:Receptors, Opioid / Q000819:agonists / Q000737:chemistry*; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D000094942:Nociceptin Receptor
chemical_list: D009292:Narcotic Antagonists; D010880:Piperidines; D011957:Receptors, Opioid; D013141:Spiro Compounds; D011392:Proline; C056291:prolinamide; D000094942:Nociceptin Receptor