Synthesis and pharmacological characterization of the selective GluK1 radioligand (S)-2-amino-3-(6-[³H]-2,4-dioxo-3,4-dihydrothieno.3,2-d] pyrimidin1(2H)- yl) propanoic acid ([³H]-NF608)

The kainic acid receptors belong to the class of ionotropic glutamate receptors and comprise five subunits named GluK1-5. Radioligands are essential tools for use in binding assays aimed at ligand-receptor structure-activity-relationship studies. Previous work has led to the synthesis of GluK1 radioligands [H-3]SYM2081, [H-3]-UBP310 and [H-3]-ATPA, however all strategies were work-intensive and thus not attractive.

Herein, we report the synthesis of [H-3]-NF608 and subsequent pharmacological evaluation at homomeric recombinant rat GluK1 receptors. Binding affinities of a series of standard GluK1 ligands were shown to be in line with previously reported affinities obtained by use of already reported radioligands.