Novel 1,3-dipropyl-8-(1-heteroarylmethyl-1 H-pyrazol-4-yl)-xanthine derivatives as high affinity and selective A 2B adenosine receptor antagonists

Abstract

A series of new 1,3-dipropyl-8-(1-heteroarylmethyl-1 H-pyrazol-4-yl)-xanthine derivatives as A 2B-AdoR antagonists have been synthesized and evaluated for their binding affinities for the A 2B, A 1, A 2A, and A 3-AdoRs. 8-(1-((3-phenyl-1,2,4-oxadiazol-5-yl)methyl)-1 H-pyrazol-4-yl)-1,3-dipropyl-1 H-purine-2,6(3 H,7 H)-dione ( 4) displayed high affinity ( K i = 1 nM) and selectivity for the A 2B-AdoR versus A 1, A 2A, and A 3-AdoRs (A 1/A 2B, A 2A/A 2B, and A 3/A 2B selectivity ratios of 370, 1100, and 480, respectively). The synthesis and SAR of this novel class of compounds are presented herein.