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Original article (peer-reviewed)

Journal ChemMedChem
Volume (Issue) 15
Page(s) 1 - 15
Title of proceedings ChemMedChem


We describe here our efforts to develop a PET tracer for imaging GluN2A-containing NMDA receptors, based on 5H-thiazolo[3,2-]pyrimidin-5-one scaffold. Metabolic stability and overall properties could be optimized satisfactorily, while binding affinities remained a limiting factor for in vivo imaging. We nevertheless identified 7-(((2-fluoroethyl)(3-fluorophenyl)amino)- methyl)-3-(2-(hydroxymethyl)cyclopropyl)-2-methyl-5H-thiazolo-[3,2-a]pyrimidin-5-one ([18F]7b) as a radioligand providing good quality images in autoradiographic studies, as well as a tritiated derivative, 2-(7-(((2-fluoroethyl)(4-fluorophenyl)amino)methyl)-2-methyl-5-oxo-5H-thiazolo[3,2-a]pyrimidin-3-yl)cyclopropane-1-carbonitrile ([3H2]11b), which was used for the successful development of a radioligand binding assay. These are valuable new tools for the study of GluN2A-containing NMDA receptors, and for the optimization of allosteric modulators binding to the pharmacophore located at the dimer interface of the GluN1−GluN2A ligand-binding domain.