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Issue 2, 2016
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Radiosynthesis and characterisation of a potent and selective GPR139 agonist radioligand

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Abstract

Compound 1 is a selective and potent agonist of the G protein-coupled receptor GPR139 (EC50 = 39 nM). In this study, we describe the synthesis, radiolabelling and in vitro evaluation of [3H]-1 for the characterisation of GPR139 and its spatial expression in the brain using autoradiography. Two different synthesis routes for the radiolabelling of 1 based on a reductive debromination strategy were investigated using deuterium (D2, g). The route based on reductive debromination of the bromonaphthyl precursor 5 proved superior over arylbromide 4 and was employed for the radiolabelling experiments. Reductive debromination of precursor 5 was accomplished using 3H2, Pd/C and triethylamine in DMF at ambient temperature to give target molecule [3H]-1 with a specific activity of 19.3 Ci mmol−1 and a radiochemical purity of ≥95%. By application of autoradiography and binding studies, it was not possible to discriminate [3H]-1 binding to wildtype mice brains from GPR139 knockout mice brains and total binding from non-specific binding in CHO-k1 cells stably expressing human GPR139 receptor. Based on these experiments we conclude that [3H]-1 is not a suitable radioligand for the characterisation of GPR139.

Graphical abstract: Radiosynthesis and characterisation of a potent and selective GPR139 agonist radioligand

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Publication details

The article was received on 14 Oct 2015, accepted on 10 Dec 2015 and first published on 17 Dec 2015


Article type: Paper
DOI: 10.1039/C5RA21326F
Citation: RSC Adv., 2016,6, 947-952
  • Open access: Creative Commons BY license
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    Radiosynthesis and characterisation of a potent and selective GPR139 agonist radioligand

    S. Kuhne, A. C. Nøhr, A. Marek, T. Elbert, A. B. Klein, H. Bräuner-Osborne, P. Wellendorph and D. S. Pedersen, RSC Adv., 2016, 6, 947
    DOI: 10.1039/C5RA21326F

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