Radiosynthesis and characterisation of a potent and selective GPR139 agonist radioligand

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Radiosynthesis and characterisation of a potent and selective GPR139 agonist radioligand

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Radiosynthesis and characterisation of a potent and selective GPR139 agonist radioligand

Popis výsledku anglicky

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.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CC - Organická chemie

OECD FORD obor

—

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

RSC Advances

ISSN

2046-2069

e-ISSN

—

Svazek periodika

6

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

6

Strana od-do

947-952

Kód UT WoS článku

000367953200014

EID výsledku v databázi Scopus

2-s2.0-84953896371