title: Importance of phenolic address groups in opioid kappa receptor selective antagonists.
abstract: In vitro characterization and comparison of JDTic, its dehydroxy analogue and nor-BNI, and its dehydroxy analogue demonstrates that the N-substituted 3,4-dimethyl-(3-hydroxyphenyl)piperidine-derived antagonist, JDTic, relies more heavily on its phenol address group for affinity and antagonist activity relative to the corresponding naltrexone derived antagonists, nor-BNI. The structural flexibility of the former class of compound relative to the latter is postulated to underlie the difference.
authors.affiliation: Chemistry and Life Sciences, Research Triangle Institute, Research Triangle Park, North Carolina 27709, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: Thomas
authors.forename: Scott E
authors.initials: SE
authors.lastname: Fix
authors.forename: Richard B
authors.initials: RB
authors.lastname: Rothman
authors.forename: S Wayne
authors.initials: SW
authors.lastname: Mascarella
authors.forename: Christina M
authors.initials: CM
authors.lastname: Dersch
authors.forename: Buddy E
authors.initials: BE
authors.lastname: Cantrell
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Zimmerman
authors.forename: F Ivy
authors.initials: FI
authors.lastname: Carroll
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D066298:In Vitro Techniques; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D010636:Phenols / Q000737:chemistry* / Q000494:pharmacology; D010880:Piperidines / Q000737:chemistry* / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines / Q000737:chemistry* / Q000494:pharmacology
chemical_list: C433814:7-hydroxy-N-(1-((4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl)methyl)-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide; D010636:Phenols; D010880:Piperidines; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D044005:Tetrahydroisoquinolines; C051844:norbinaltorphimine; D009271:Naltrexone