Synthesis and pharmacological evaluation of novel 1- and 8-substituted-3-furfuryl xanthines as adenosine receptor antagonists

The synthesis of an important set of 3-furfurylxanthine derivatives is described. Binding affinities were determined for rat A1 and human A2A, A2B and A3 receptors. Several of the 3-furfuryl-7-methylxanthine derivatives showed moderate-to-high affinity at human A2B receptors, the most active compound (10d) having a Ki of 7.4 nM for hA2B receptors, with selectivities over rA1 and hA2A receptors up to 14-fold and 11-fold, respectively. Affinities for hA3 receptors were very low for all members of the set.

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