Synthesis and First Evaluation of [¹⁸F]Fluorocyano- and [¹⁸F]Fluoronitroquinoxalinedione as Putative AMPA Receptor Antagonists

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 K_i-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.

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