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 A2a-adenosine receptors, while havi ng little effect on affinity at Al-adenosine receptors. In contrast, a n aryl p-(trifluoromethyl) substituent has little effect on affinity o f 3,7-disubstituted and 1,3,7-trisubstituted 8-phenylxanthines. An ary l p-sulfo substituent reduces affinity of all 8-phenylxanthines at A1- and A2a-adenosine receptors. An 8-(trifluoromethyl) substituent marked ly reduces affinity of 1,3-dialkylxanthines at both A1- and A2a-adenos ine receptors. In contrast, 8-(trifluoromethyl)caffeine retains affini ty for A2a-adenosine receptors, but does lose affinity for A1-adenosin e receptors. 8-Bromo-, 8-acryl-, and 8-pent-1-enylcaffeines are also s elective for A2-adenosine receptors, while 8-cyclobutylcaffeine is non selective. 8-[trans-2-(tert-butyloxycarbonyl)vinylcaffeine is 20-fold selective for Aza vs A1 receptors.