1,3-Dipropyl-8-(1-phenylacetamide-1 H-pyrazol-3-yl)-xanthine derivatives as highly potent and selective human A 2B adenosine receptor antagonists

Abstract

A new series of 1,3-dipropyl-8-(1-phenylacetamide-1 H-pyrazol-3-yl)-xanthine derivatives has been identified as potent A 2B adenosine receptor antagonists. The products have been evaluated for their binding affinities for the human A 2B, A 1, A 2A, and A 3 adenosine receptors. N-(4-chloro-phenyl)-2-[3-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1 H-purin-8-yl)-5-methyl-pyrazol-1-yl] ( 11c) showed a high affinity for the human A 2B adenosine receptor K i = 7 nM and good selectivity (A 1, A 2A, A 3/A 2B > 140). Synthesis and SAR of this novel class of compounds is presented herein.