Novel 8-(p-substituted-phenyl/benzyl)xanthines with selectivity for the A2A adenosine receptor possess bronchospasmolytic activity

A new series of 8-(p-substituted-phenyl/benzyl)xanthines has been synthesized and evaluated in vitro for adenosine receptor binding affinity and in vivo for bronchospasmolytic effects. It was observed that the nature of substituent at para-position of 8-phenyl/benzyl group on the xanthine scaffold remarkably affects the binding affinity and selectivity of xanthine derivatives for various adenosine receptor subtypes and also their bronchospasmolytic effects. Newly synthesized 8-phenylxanthines displayed potent binding affinity and significant selectivity for A(2A) receptors and also produced potent bronchospasmolytic effects. Replacement of phenyl ring with benzyl moiety at C-8 of xanthine skeleton resulted in notable reduction in adenosine receptor affinity and broncholytic effects. (C) 2014 Elsevier Masson SAS. All rights reserved.