Synthesis of novel 1-alkyl-8-substituted-3-(3-methoxypropyl) xanthines as putative A2B receptor antagonists

In order to identify a high-affinity, selective antagonist for the A2B subtype adenosine receptor, more than 40 1,8-disubstituted-3-(3-methoxypropyl) xanthines were prepared and evaluated for their binding affinity at recombinant human adenosine receptors, mainly of the A2A and A2B subtypes. Some of the 1-ethyl-3-(3-methoxypropyl)-8-aryl substituted derivatives 15(a-m) showed moderate-to-high affinity at human A2B receptors, with compound 15d showing A2B selectivity over the other A receptors assayed (A1, A2A, A3) of 34-fold or over. © 2009 Elsevier Ltd. All rights reserved.