XANTHINES WITH C-8 CHIRAL SUBSTITUENTS AS POTENT AND SELECTIVE ADENOSINE A(1) ANTAGONISTS

Several 8-substituted 1,3-dipropylxanthines were synthesized, and thei r receptor binding affinities at adenosine A(1) and A(2) receptors wer e measured. When enantiomeric pairs of compounds were examined, the R enantiomers were significantly more potent than the corresponding S en antiomers. The most potent compound at the A(1) receptor was hyl-2-phe nylethy)-1,3-dipropyl-1H-purine-2,6-dione (5a; MDL 102,503), whose K-i value at the A(1) receptor was 6.9 nM. However, a more selective comp ound was -(1-phenylpropyl)-1,3-dipropyl-1H-purine-2,6-dione (5d; MDL 1 02,234), which had a K-i value of 23.2 nM at the A(1) receptor and an A(2)/A(1) ratio of 153.