title: Discovery of the first N-substituted 4beta-methyl-5-(3-hydroxyphenyl)morphan to possess highly potent and selective opioid delta receptor antagonist activity.
abstract: A structurally novel opioid delta receptor selective antagonist has been identified. This compound, (+)-5-(3-hydroxyphenyl)-4-methyl-2-(3-phenylpropyl)-2-azabicyclo[3.3.1]non-7-yl-(1-phenyl-1-cyclopentane)carboxamide [(+)-KF4, (+)-4], showed a K(e) value of 0.15 nM in the [(35)S]GTPgammaS functional assay. (+)-KF4 is also a delta inverse agonist with an IC(50) value of 1.8 nM. To our knowledge, this is the first potent and selective delta opioid receptor antagonist from the 5-phenylmorphan class of opioids.
authors.affiliation: Chemistry and Life Sciences, Research Triangle Institute, Research Triangle Park, North Carolina 27709, USA. fic@rti.org
authors.forename: F Ivy
authors.initials: FI
authors.lastname: Carroll
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: S Wayne
authors.initials: SW
authors.lastname: Mascarella
authors.forename: Hernán A
authors.initials: HA
authors.lastname: Navarro
authors.forename: Richard B
authors.initials: RB
authors.lastname: Rothman
authors.forename: Buddy E
authors.initials: BE
authors.lastname: Cantrell
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Zimmerman
authors.forename: James B
authors.initials: JB
authors.lastname: Thomas
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D011869:Radioligand Assay; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: C482215:5-(3-hydroxyphenyl)-4-methyl-2-(3-phenylpropyl)-2-azabicyclo(3.3.1)non-7-yl-(1-phenyl-1-cyclopentane)carboxamide; D019086:Bridged Bicyclo Compounds, Heterocyclic; D017465:Receptors, Opioid, delta