title: Opioid bifunctional ligands from morphine and the opioid pharmacophore Dmt-Tic.
abstract: Bifunctional ligands containing an ester linkage between morphine and the δ-selective pharmacophore Dmt-Tic were synthesized, and their binding affinity and functional bioactivity at the μ, δ and κ opioid receptors determined. Bifunctional ligands containing or not a spacer of β-alanine between the two pharmacophores lose the μ agonism deriving from morphine becoming partial μ agonists 4 or μ antagonists 5. Partial κ agonism is evidenced only for compound 4. Finally, both compounds showed potent δ antagonism.
authors.affiliation: Department of Toxicology, University of Cagliari, Via Ospedale 72, I-09124 Cagliari, Italy. gbalboni@unica.it
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Balboni
authors.forename: Severo
authors.initials: S
authors.lastname: Salvadori
authors.forename: Ewa D
authors.initials: ED
authors.lastname: Marczak
authors.forename: Brian I
authors.initials: BI
authors.lastname: Knapp
authors.forename: Jean M
authors.initials: JM
authors.lastname: Bidlack
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Lazarus
authors.forename: Xuemei
authors.initials: X
authors.lastname: Peng
authors.forename: Yu Gui
authors.initials: YG
authors.lastname: Si
authors.forename: John L
authors.initials: JL
authors.lastname: Neumeyer
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D008968:Molecular Conformation; D009020:Morphine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009292:Narcotic Antagonists; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C446951:2',6'-dimethyltyrosyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid; D004151:Dipeptides; D004952:Esters; D008024:Ligands; D009292:Narcotic Antagonists; D044005:Tetrahydroisoquinolines; D009020:Morphine