Radiosynthesis of N-[4-(4-fluorobenzyl)piperidin-1-yl]-N′-(2-[11C]oxo-1,3-dihydrobenzimidazol-5-yl)oxamide, a NR2B-selective NMDA receptor antagonist

• Published in: Journal of labelled compounds & radiopharmaceuticals Vol. 53; no. 2; pp. 63 - 67
• Main Authors: Labas, Romain, Sobrio, Franck, Bramoullé, Yann, Hérard, Anne-Sophie, Guillermier, Martine, Hantraye, Philippe, Dollé, Frédéric, Barré, Louisa
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.02.2010; Wiley
• Subjects: Biochemical Research Methods; Biochemistry & Molecular Biology; Biological and medical sciences; carbon-11; Chemistry; Chemistry, Analytical; Chemistry, Medicinal; Contrast media. Radiopharmaceuticals; Life Sciences & Biomedicine; Medical sciences; NMDA; NR2B; PET; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Physical Sciences; radiolabelling; Science & Technology; NR2B; NMDA; carbon-11; radiolabelling; LIGAND; PET; Methane; Purification; Radiolabelling; Phosgene; Carbon Isotopes; HPLC chromatography; Glutamate receptor; Selectivity; Carbonyl Chlorides; Benzimidazole derivatives; Piperidine derivatives; Carbon 11; Antagonist; Fluorine Organic compounds; NMDA receptor; Chemical synthesis
• ISSN: 0362-4803; 1099-1344
• DOI: 10.1002/jlcr.1702

In order to perform in vivo imaging of the NR2B NMDA receptor system by positron emission tomography, a NR2B selective NMDA receptor antagonist has been labelled with carbon‐11 (half‐life: 20 min). N‐[4‐(4‐fluorobenzyl)piperidin‐1‐yl]‐N′‐(2‐oxo‐1,3‐dihydrobenzimidazol‐5‐yl)oxamide has been described demonstrating high affinity and selectivity for the NR2B receptors (IC50 of 5 nM in [3H]Ro‐25,6981 binding assay). The labelling precursor and the reference compound were synthesized by coupling the 4‐(4‐fluorobenzyl)piperidine with the corresponding oxalamic acid. The reaction of [11C]phosgene with phenylenediamine precursor led the formation of the [11C]benzimidazolone ring present on the ligand. The labelling occurred in THF or acetonitrile and the decay corrected radiochemical yield was 30–40% from the produced [11C]methane. HPLC purification and formulation led to 2.6–3.7 GBq (70–100 mCi) of radioligand within 30–35 min. The specific radioactivity was 72–127 GBq/µmol (2–3.4 Ci/µmol) at the end of synthesis. Copyright © 2009 John Wiley & Sons, Ltd. N‐[4‐(4‐Fluorobenzyl)piperidin‐1‐yl]‐N′‐(2‐oxo‐1,3‐dihydrobenzimidazol‐5‐yl) oxamide has been described as a high‐affinity antagonist for NR2B selective subtype NMDA receptor. This compound has been labelled by cyclization reaction with [11C]phosgene leading to the [11C]benzimidazolone ring. The decay corrected radiochemical yield was 30–40% from the produced [11C]methane affording 2.6–3.7 GBq (70–100 mCi) of radioligand within 30–35 min including HPLC purification and formulation. Copyright © 2009 John Wiley & Sons, Ltd.