Synthesis and preliminaryin vivo evaluation of 4-[18F]fluoro-N-{2-[4-(6-trifluoromethylpyridin-2-yl)piperazin-1-yl]ethyl}benzamide, a potential PET radioligand for the 5-HT1A receptor
| Autor: | Guido Slegers, F. De Vos, Filip Dumont, D. Leysen, Rudi Dierckx, Karel Strijckmans, Marleen Vandecapelle, Kurt Audenaert |
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| Rok vydání: | 2004 |
| Předmět: |
Stereochemistry
Organic Chemistry Total synthesis Electrophilic aromatic substitution Biochemistry Chemical synthesis Analytical Chemistry Piperazine chemistry.chemical_compound chemistry Nucleophilic aromatic substitution Drug Discovery Nitro Radioligand Radiology Nuclear Medicine and imaging Benzamide Spectroscopy Nuclear chemistry |
| Zdroj: | Journal of Labelled Compounds and Radiopharmaceuticals. 47:531-542 |
| ISSN: | 1099-1344 0362-4803 |
| Popis: | 4-Fluoro-N-{2-[4-(6-trifluoromethylpyridin-2-yl)piperazin-1-yl]ethyl}benzamide is a full 5-HT1A agonist with high affinity (pKi=9.3), selectivity and a c log P of 3.045. The corresponding PET radioligand 4-[18F]fluoro-N-{2-[4-(6-trifluoromethylpyridin-2-yl)piperazin-1-yl]ethyl}benzamide was synthesized by nucleophilic aromatic substitution on the nitro precursor. The fluorinating agent K[18F]F/Kryptofix 2.2.2 was both dried (9 min, 700 W) and incorporated in the precursor (5 min, 700 W) using a commercially available microwave oven. In a total synthesis time of 60 min, an overall radiochemical yield of 18% (SD=5, n=7, EOS) was obtained. Radiochemical purity was always higher than 99% and specific activity always higher than 81.4 GBq/µmol (2.2 Ci/µmol). Initial brain uptake in mice was 2.19% ID (5.47% ID/g, 2 min) but decreased rapidly (0.17% ID, 0.45% ID/g (60 min)). During the first 20 min p.i., radioactivity concentration of the brain was significantly higher than that of blood demonstrating good brain entry of the tracer. Copyright © 2004 John Wiley & Sons, Ltd. |
| Databáze: | OpenAIRE |
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