Derisking the Cu-Mediated 18F-Fluorination of Heterocyclic Positron Emission Tomography Radioligands
| Autor: | Matthew Tredwell, Michael Schedler, Christophe Genicot, Joël Mercier, Véronique Gouverneur, Sean Preshlock, Enrico Emer, Stefan Verhoog, Nicholas J. Taylor |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
medicine.diagnostic_test
010405 organic chemistry Drug discovery Chemistry Aryl Radiosynthesis General Chemistry 010402 general chemistry 01 natural sciences Biochemistry Combinatorial chemistry Catalysis 0104 chemical sciences chemistry.chemical_compound Colloid and Surface Chemistry Drug development Positron emission tomography Reagent medicine Molecule Organic chemistry |
| Zdroj: | Journal of the American Chemical Society. 139:8267-8276 |
| ISSN: | 1520-5126 0002-7863 |
| Popis: | Molecules labeled with fluorine-18 ((18)F) are used in positron emission tomography to visualize, characterize and measure biological processes in the body. Despite recent advances in the incorporation of (18)F onto arenes, the development of general and efficient approaches to label radioligands necessary for drug discovery programs remains a significant task. This full account describes a derisking approach toward the radiosynthesis of heterocyclic positron emission tomography (PET) radioligands using the copper-mediated (18)F-fluorination of aryl boron reagents with (18)F-fluoride as a model reaction. This approach is based on a study examining how the presence of heterocycles commonly used in drug development affects the efficiency of (18)F-fluorination for a representative aryl boron reagent, and on the labeling of more than 50 (hetero)aryl boronic esters. This set of data allows for the application of this derisking strategy to the successful radiosynthesis of seven structurally complex pharmaceutically relevant heterocycle-containing molecules. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|