Radiosynthesis and characterisation of a potent and selective GPR139 agonist radioligand

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F16%3A00458617" target="_blank" >RIV/61388963:_____/16:00458617 - isvavai.cz</a>
Result on the web
<a href="http://pubs.rsc.org/en/content/articlehtml/2016/ra/c5ra21326f" target="_blank" >http://pubs.rsc.org/en/content/articlehtml/2016/ra/c5ra21326f</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1039/c5ra21326f" target="_blank" >10.1039/c5ra21326f</a>

Result language
angličtina
Original language name
Radiosynthesis and characterisation of a potent and selective GPR139 agonist radioligand
Original language description
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 [H-3]-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 (D-2, 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 H-3(2), Pd/C and triethylamine in DMF at ambient temperature to give target molecule [H-3]-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 [H-3]-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 [H-3]-1 is not a suitable radioligand for the characterisation of GPR139.
Czech name
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Czech description
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Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
CC - Organic chemistry
OECD FORD branch
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Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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