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Radiosynthesis of novel 18 F‐labelled derivatives of indiplon as potential GABA A receptor imaging tracers for PET
Author(s) -
Fischer Steffen,
Hiller Achim,
Scheunemann Matthias,
DeutherConrad Winnie,
Hoepping Alexander,
Diekers Michael,
Wegner Florian,
Brust Peter,
Steinbach Jörg
Publication year - 2008
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.1473
Subject(s) - radiosynthesis , chemistry , tosyl , gabaa receptor , receptor , yield (engineering) , nucleophilic substitution , specific activity , nucleophile , pet imaging , high performance liquid chromatography , stereochemistry , medicinal chemistry , chromatography , organic chemistry , positron emission tomography , biochemistry , nuclear medicine , enzyme , catalysis , medicine , materials science , metallurgy
The involvement of gamma amino butyric acid (GABA) receptors in a variety of neurological and psychiatric diseases has promoted the development and use of radiolabelled benzodiazepines (BZ) for brain imaging by PET. However, these radioligands are unable to distinguish between the various subtypes of GABA A receptors. Novel non‐BZ such as the pyrazolo‐pyrimidine indiplon proved to be selective for the α 1 ‐subunit of the GABA A receptor. Here, we describe the syntheses of four novel 18 F‐labelled indiplon derivatives. Radiosyntheses were performed via n.c.a. 18 F‐nucleophilic substitution starting from the tosyl, bromo, and 4‐nitrobenzoyl precursors to obtain fluorine substituted N ‐alkylamide side chain derivatives of indiplon, followed by multistep purification using semi‐preparative high‐performance liquid chromatography and solid phase extraction. Tosyl and bromo precursors were converted into 18 F‐labelled indiplon derivatives with good and reproducible radiochemical yield (RCY) (35–70%, decay corrected), high radiochemical purity (≥98.5%), and high specific activity ( > 150 GBq/µmol). By contrast, a low RCY (5–10%) and specific activity (10–15 GBq/µmol) were achieved for the 4‐nitrobenzoyl precursor. Copyright © 2008 John Wiley & Sons, Ltd.