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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)-16 as suitable parent molecules for ¹⁸F-labeled positron emission tomography (PET) radiotracers to enable future investigation of GhrR in the brain.

SUBMITTER: Moldovan RP

PROVIDER: S-EPMC5412352 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Development of Fluorinated Non-Peptidic Ghrelin Receptor Ligands for Potential Use in Molecular Imaging.

Moldovan Rareş-Petru RP Els-Heindl Sylvia S Worm Dennis J DJ Kniess Torsten T Kluge Michael M Beck-Sickinger Annette G AG Deuther-Conrad Winnie W Krügel Ute U Brust Peter P

International journal of molecular sciences 20170405 4

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 eval ...[more]

PMID: 28379199

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