Prodrug Approach toward the Development of a PET Radioligand for Imaging the GluN2A Subunits of the NMDA Receptor

A straightforward synthesis of a fluorine-18-labeled prodrug of AFA233 is reported. The key step in the preparation of [F-18]AFA233-prodrug is the selective deprotection of the tert-butyl protection groups of the quinoxalinedione moiety without cleavage of the tert-butyl-S-acyl-2-thioethyl protection groups on the phosphate esters. In addition, the preparation of the nonradioactive prodrug reference compound of AFA233 is reported.

Automated summary

A direct synthesis of a fluorine-18-labeled prodrug of AFA233 was achieved by selectively deprotecting tert-butyl protection groups on the quinoxalinedione moiety, without affecting the tert-butyl-S-acyl-2-thioethyl protection groups on the phosphate esters. Additionally, a nonradioactive prodrug reference compound of AFA233 was prepared.