Synthesis and evaluation of 7-amino-2-(2(3)-furyl)-5-phenylethylamino-oxazolo[5,4-d]pyrimidines as potential A2A adenosine receptor antagonists for positron emission tomography (PET).
The brain A2A adenosine receptor (A2AAR) participates with the dopamine D2 receptor in the control of movement and also might influence behavior. Because PET is an important tool for studying the roles of receptors in disease, a ligand for imaging the brain A2AAR is desirable. This report describes the synthesis and A2AAR antagonist activities of a panel of phenyl-substituted 7-amino-2-(2-furyl)-5-phenylethylamino-oxazolo[5,4-d]pyrimidines, 11aa-af, and their 3-furyl congeners, 11ba-bd. In competitive binding studies all compounds displaced [3H]CGS21680 from the A2AAR with Ki values of 14-33 nM with selectivity for the A2AAR over the A1AR of 5- to 94-fold. Autoradiography of brain sections showed a high level of unspecific binding that obscured specific binding. Thus, these compounds are not promising PET ligands.
Holschbach
Marcus H
MH
Institut für Nuklearchemie, Forschungszentrum Jülich GmbH, D-52425 Jülich, Germany. m.holschbach@fz-juelich.de
Bier
Dirk
D
Stüsgen
Stefan
S
Wutz
Walter
W
Sihver
Wiebke
W
Coenen
Heinz H
HH
Olsson
Ray A
RA
D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D008024:Ligands; D015394:Molecular Structure; D049268:Positron-Emission Tomography; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011869:Radioligand Assay; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D013329:Structure-Activity Relationship; D013552:Swine
D058917:Adenosine A2 Receptor Antagonists; D008024:Ligands; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A