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

Stefan Gruber; Valérie Waser; Zacharias Thiel; Simon M Ametamey

doi:10.1021/acs.orglett.1c01274

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

Org Lett. 2021 Jun 18;23(12):4584-4587. doi: 10.1021/acs.orglett.1c01274. Epub 2021 Jun 1.

Authors

Stefan Gruber¹, Valérie Waser¹, Zacharias Thiel¹, Simon M Ametamey¹

Affiliation

¹ Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Vladimir-Prelog-Weg 4, Zurich 8093, Switzerland.

PMID: 34060848
DOI: 10.1021/acs.orglett.1c01274

Abstract

A straightforward synthesis of a fluorine-18-labeled prodrug of AFA233 is reported. The key step in the preparation of [¹⁸F]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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Fluorine Radioisotopes / chemistry*
Molecular Structure
Positron-Emission Tomography / methods*
Prodrugs / chemistry*
Radiopharmaceuticals / chemical synthesis*
Receptors, N-Methyl-D-Aspartate / chemistry*

Substances

Fluorine Radioisotopes
Prodrugs
Radiopharmaceuticals
Receptors, N-Methyl-D-Aspartate
Fluorine-18
N-methyl D-aspartate receptor subtype 2A