Synthesis and pharmacological evaluation of novel substituted 9-deazaxanthines as A2B receptor antagonists

A new series of 9-deazaxanthine derivatives with various substituents at the heterocyclic system were synthesized and evaluated for their binding affinities for the four human recombinant adenosine receptors, A1–A3 subtypes. A number of the 9-deazaxanthines derivatives 3a–m showed moderate-to-high affinity for hA2B receptors, with compound 3f showing a 32-fold selectivity for A2B over A1 and a 2750-fold selectivity for A2B over A2A.

Graphical abstractA new series of 9-deazaxanthine derivatives with various substituents in the ring were synthesized and evaluated for their binding affinities for the four human recombinant adenosine receptors.Figure optionsDownload full-size imageDownload as PowerPoint slide