The development of potential new fluorine-18 labelled radiotracers for imaging the GABAA receptor
| Autor: | Mark Battle, Alessandra Gaeta, Dennis O'shea, Penny Hao Zheng, Julian Goggi, Stuart Plant, Benedicte Guilbert, Samantha L. Brown, Amanda Ewan, Paul A. Jones, John Woodcraft, Alexander Jackson, Denis Raymond Christophe Bouvet, William Trigg, Clare Jones |
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| Rok vydání: | 2013 |
| Předmět: |
Flumazenil
Fluorine Radioisotopes medicine.drug_class Clinical Biochemistry Pharmaceutical Science Biochemistry Small Molecule Libraries chemistry.chemical_compound In vivo Amide Drug Discovery medicine Humans Moiety Molecular Biology Benzodiazepine medicine.diagnostic_test GABAA receptor Chemistry Organic Chemistry Radiochemistry Receptors GABA-A In vitro Positron emission tomography Positron-Emission Tomography Molecular Medicine Radiopharmaceuticals medicine.drug Nuclear chemistry |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 23:821-826 |
| ISSN: | 0960-894X |
| Popis: | Positron emission tomography (PET) using the tracer [(11)C]Flumazenil has shown changes in the distribution and expression of the GABA(A) receptor in a range of neurological conditions and injury states. We aim to develop a fluorine-18 labelled PET agent with comparable properties to [(11)C]Flumazenil. In this study we make a direct comparison between the currently known fluorine-18 labelled GABA(A) radiotracers and novel imidazobenzodiazepine ligands. A focussed library of novel compound was designed and synthesised where the fluorine containing moiety and the position of attachment is varied. The in vitro affinity of twenty-two compounds for the GABA(A) receptor was measured. Compounds containing a fluoroalkyl amide or a longer chain ester group were eliminated due to low potency. The fluorine-18 radiochemistry of one compound from each structural type was assessed to confirm that an automated radiosynthesis in good yield was feasible. Eleven of the novel compounds assessed appeared suitable for in vivo assessment as PET tracers. |
| Databáze: | OpenAIRE |
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