title: 4-Phenyl-4-[1H-imidazol-2-yl]-piperidine derivatives, a novel class of selective delta-opioid agonists.
abstract: A novel series of 4-phenyl-4-[1H-imidazol-2-yl]-piperidine derivatives has been prepared and their synthesis described herein. In vitro affinities for delta-, mu-, and kappa-opioid receptors, as well as the functional activity in the [(35)S]GTPgammaS assay are reported. The most potent and selective delta-opioid agonist 18a exhibited a K(i) of 18 nM, and was >258-fold and 28-fold selective over mu- and kappa-receptors, respectively; the compound is a full agonist with an EC(50) value of 14 nM.
authors.affiliation: Division of Psychiatry, Research and Early Development Europe, Johnson and Johnson Pharmaceutical Research and Development, Jarama 75, 47007 Toledo, Spain. atrabanc@prdes.jnj.com
authors.forename: Andrés A
authors.initials: AA
authors.lastname: Trabanco
authors.forename: Shirley
authors.initials: S
authors.lastname: Pullan
authors.forename: José M
authors.initials: JM
authors.lastname: Alonso
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Alvarez
authors.forename: José I
authors.initials: JI
authors.lastname: Andrés
authors.forename: Inge
authors.initials: I
authors.lastname: Boeckx
authors.forename: Javier
authors.initials: J
authors.lastname: Fernández
authors.forename: Antonio
authors.initials: A
authors.lastname: Gómez
authors.forename: Laura
authors.initials: L
authors.lastname: Iturrino
authors.forename: Frans E
authors.initials: FE
authors.lastname: Janssens
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Leenaerts
authors.forename: Ana I
authors.initials: AI
authors.lastname: De Lucas
authors.forename: Encarna
authors.initials: E
authors.lastname: Matesanz
authors.forename: Theo
authors.initials: T
authors.lastname: Meert
authors.forename: Thomas
authors.initials: T
authors.lastname: Steckler
mesh_terms: D001667:Binding, Competitive; D015195:Drug Design; D004345:Drug Industry / Q000379:methods*; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D008956:Models, Chemical; D010455:Peptides / Q000737:chemistry; D010880:Piperidines / Q000737:chemistry* / Q000494:pharmacology*; D017465:Receptors, Opioid, delta / Q000819:agonists*; D013329:Structure-Activity Relationship
chemical_list: C508741:4-phenyl-4-(1H-imidazol-2-yl)piperidine; D007093:Imidazoles; D010455:Peptides; D010880:Piperidines; D017465:Receptors, Opioid, delta; C032727:piperidine