New pyrrolopyrimidin-6-yl benzenesulfonamides: Potent A 2B adenosine receptor antagonists

Abstract

A new series of 4-(1,3-dialkyl-2,4-dioxo-2,3,4,5-tetrahydro-1 H-pyrrolo[3,2- d]pyrimidin-6-yl)benzenesulfonamides 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 and A 3 adenosine receptors. 6-(4-{[4-(4-Bromobenzyl)piperazin-1-yl]sulfonyl}phenyl)-1,3-dimethyl-1 H-pyrrolo[3,2- d]pyrimidine-2,4(3 H,5 H)-dione ( 16) showed a high affinity for the A 2B adenosine receptor (IC 50 = 1 nM) and selectivity (A 1: 183x; A 3: 12660x). Synthesis and SAR of this novel class of compounds showing improved absorption properties is presented herein.