title: Synthesis and evaluation of three structurally related ¹⁸F-labeled orvinols of different intrinsic activities: 6-O-[¹⁸F]fluoroethyl-diprenorphine ([¹⁸F]FDPN), 6-O-[¹⁸F]fluoroethyl-buprenorphine ([¹⁸F]FBPN), and 6-O-[¹⁸F]fluoroethyl-phenethyl-orvinol ([¹⁸F]FPEO).
abstract: We report the synthesis and biological evaluation of a triplet of 6-O-(18)F-fluoroethylated derivatives of structurally related orvinols that span across the full range of intrinsic activities, the antagonist diprenorphine, the partial agonist buprenorphine, and the full agonist phenethyl-orvinol. [(18)F]fluoroethyl-diprenorphine, [(18)F]fluoroethyl-buprenorphine, and [(18)F]fluoroethyl-phenethyl-orvinol were prepared in high yields and quality from their 6-O-desmethyl-precursors. The results indicate suitable properties of the three 6-O-(18)F-fluoroethylated derivatives as functional analogues to the native carbon-11 labeled versions with similar pharmacological properties.
authors.affiliation: Department of Chemistry, University of Oslo , P.O. Box 1033, Blindern, N-0315 Oslo, Norway.
authors.forename: Bent W
authors.initials: BW
authors.lastname: Schoultz
authors.forename: Trine
authors.initials: T
authors.lastname: Hjørnevik
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Reed
authors.forename: János
authors.initials: J
authors.lastname: Marton
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Coello
authors.forename: Frode
authors.initials: F
authors.lastname: Willoch
authors.forename: Gjermund
authors.initials: G
authors.lastname: Henriksen
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002047:Buprenorphine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D016466:CHO Cells; D002250:Carbon Radioisotopes; D003412:Cricetulus; D004174:Diprenorphine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D005462:Fluorine Radioisotopes; D006801:Humans; D009019:Morphinans / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D009292:Narcotic Antagonists; D049268:Positron-Emission Tomography; D011869:Radioligand Assay; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D011957:Receptors, Opioid / Q000819:agonists / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C000591356:6-O-(2-fluoroethyl)buprenorphine; C000591355:6-O-(2-fluoroethyl)diprenorphine; C000591357:6-O-(2-fluoroethyl)phenethylorvinol; D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D009019:Morphinans; D009292:Narcotic Antagonists; D019275:Radiopharmaceuticals; D011957:Receptors, Opioid; D004174:Diprenorphine; D002047:Buprenorphine