Abstract
Derivatives of quinoxalinedione (QX) were chosen as chemical lead for the development of new radioligands of the AMPA receptor, since there are several examples of QX-derivatives with high affinity. The radiosyntheses of the new compounds 6-[18F]fluoro-7-nitro-QX ([18F]FNQX) and 7-[18F]fluoro-6-cyano-QX ([18F]FCQX) with radiochemical yields of 8 ± 2 and 3 ± 2 %, respectively, as well as the evaluation of their binding properties to the AMPA-receptor were performed. A comparison of the Ki-values of the new QX-derivatives FCQX and FNQX with mono-substituted cyanoand nitro-QX shows negligibly small differences of affinity (within the range of 1.4 to 5 µM), but exhibits a tenfold lower affinity than derivatives with two electron withdrawing groups like the 7-cyano-6-nitro-compound CNQX and the 6,7- dinitro compound DNQX. Thus, with respect to the low affinity and a high non-specific binding with in vitro and ex vivo autoradiographic studies, the new compounds do not lend themselves for in vivo imaging.
Keywords: AMPA receptor, fluorine-18, glutamate receptor, positron emission tomography, quinoxalinedione, radiofluorination.
Graphical Abstract
Medicinal Chemistry
Title:Synthesis and First Evaluation of [18F]Fluorocyano- and [18F]Fluoronitroquinoxalinedione as Putative AMPA Receptor Antagonists
Volume: 11 Issue: 1
Author(s): Sebastian Olma, Johannes Ermert, Wiebke Sihver and Heinz H. Coenen
Affiliation:
Keywords: AMPA receptor, fluorine-18, glutamate receptor, positron emission tomography, quinoxalinedione, radiofluorination.
Abstract: Derivatives of quinoxalinedione (QX) were chosen as chemical lead for the development of new radioligands of the AMPA receptor, since there are several examples of QX-derivatives with high affinity. The radiosyntheses of the new compounds 6-[18F]fluoro-7-nitro-QX ([18F]FNQX) and 7-[18F]fluoro-6-cyano-QX ([18F]FCQX) with radiochemical yields of 8 ± 2 and 3 ± 2 %, respectively, as well as the evaluation of their binding properties to the AMPA-receptor were performed. A comparison of the Ki-values of the new QX-derivatives FCQX and FNQX with mono-substituted cyanoand nitro-QX shows negligibly small differences of affinity (within the range of 1.4 to 5 µM), but exhibits a tenfold lower affinity than derivatives with two electron withdrawing groups like the 7-cyano-6-nitro-compound CNQX and the 6,7- dinitro compound DNQX. Thus, with respect to the low affinity and a high non-specific binding with in vitro and ex vivo autoradiographic studies, the new compounds do not lend themselves for in vivo imaging.
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Cite this article as:
Olma Sebastian, Ermert Johannes, Sihver Wiebke and Coenen H. Heinz, Synthesis and First Evaluation of [18F]Fluorocyano- and [18F]Fluoronitroquinoxalinedione as Putative AMPA Receptor Antagonists, Medicinal Chemistry 2015; 11 (1) . https://dx.doi.org/10.2174/1573406410666140428151318
DOI https://dx.doi.org/10.2174/1573406410666140428151318 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |

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