Effect of trifluoromethyl and other substituents on activity of xanthines at adenosine receptors.

An aryl p-(trifluoromethyl) substituent increases the affinity of 1,3-disubstituted 8-phenylxanthines at A 2a -adenosine receptors, while having little effect on affinity at A 1 -adenosine receptors. In contrast, an aryl p-(trifluoromethyl) substituent has little effect on affinity of 3,7-disubstituted and 1,3,7-trisubstituted 8-phenylxanthines. An aryl p-sulfo substituent reduces affinity of all 8-phenylxanthines at A 1 - and A 2a -adenosine receptors. An 8-(trifluoromethyl) substituent markedly reduces affinity of 1,3-dialkylxanthines at both A 1 - and A 2a -adenosine receptors