title: Development of Fluorinated Non-Peptidic Ghrelin Receptor Ligands for Potential Use in Molecular Imaging.
abstract: The ghrelin receptor (GhrR) is a widely investigated target in several diseases. However, the current knowledge of its role and distribution in the brain is limited. Recently, the small and non-peptidic compound (S)-6-(4-bromo-2-fluorophenoxy)-3-((1-isopropylpiperidin-3-yl)methyl)-2-methylpyrido[3,2-d]pyrimidin-4(3H)-one ((S)-9) has been described as a GhrR ligand with high binding affinity. Here, we describe the synthesis of fluorinated derivatives, the in vitro evaluation of their potency as partial agonists and selectivity at GhrRs, and their physicochemical properties. These results identified compounds (S)-9, (R)-9, and (S)-16as suitable parent molecules for18F-labeled positron emission tomography (PET) radiotracers to enable future investigation of GhrR in the brain.
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf e. V., Institute of Radiopharmaceutical Cancer Research, 04318 Leipzig, Germany. r.moldovan@hzdr.de.
authors.forename: Rareş-Petru
authors.initials: RP
authors.lastname: Moldovan
authors.affiliation: Institute of Biochemistry, Universität Leipzig, 04103 Leipzig, Germany. sylvia.els@uni-leipzig.de.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Els-Heindl
authors.affiliation: Institute of Biochemistry, Universität Leipzig, 04103 Leipzig, Germany. dennis.worm@uni-leipzig.de.
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Worm
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf e. V., Institute of Radiopharmaceutical Cancer Research, 04318 Leipzig, Germany. t.kniess@hzdr.de.
authors.forename: Torsten
authors.initials: T
authors.lastname: Kniess
authors.affiliation: Department of Psychiatry, Universität Leipzig, 04103 Leipzig, Germany. Michael.Kluge@medizin.uni-leipzig.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Kluge
authors.affiliation: Institute of Biochemistry, Universität Leipzig, 04103 Leipzig, Germany. abeck-sickinger@uni-leipzig.de.
authors.forename: Annette G
authors.initials: AG
authors.lastname: Beck-Sickinger
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf e. V., Institute of Radiopharmaceutical Cancer Research, 04318 Leipzig, Germany. w.deuther-conrad@hzdr.de.
authors.forename: Winnie
authors.initials: W
authors.lastname: Deuther-Conrad
authors.affiliation: Rudolf Boehm Institute of Pharmacology and Toxicology, Medical Faculty, Universität Leipzig, 04107 Leipzig, Germany. ute.kruegel@medizin.uni-leipzig.de.
authors.forename: Ute
authors.initials: U
authors.lastname: Krügel
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf e. V., Institute of Radiopharmaceutical Cancer Research, 04318 Leipzig, Germany. p.brust@hzdr.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Brust
mesh_terms: D000818:Animals; D016466:CHO Cells; D002352:Carrier Proteins / Q000378:metabolism*; D003412:Cricetulus; D054879:Halogenation; D006801:Humans; D008024:Ligands; D057054:Molecular Imaging / Q000379:methods*; D015394:Molecular Structure; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D008024:Ligands; D011743:Pyrimidines; D019275:Radiopharmaceuticals; C051815:somatotropin-binding protein
keywords: brain; fluorine; ghrelin receptor; positron emission tomography