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

• Novel A2A selective 8-(p-substituted-phenyl/benzyl)xanthines have been synthesized.
• The compounds were studied for AR binding affinity and bronchospasmolytic effects.
• Nature of para 8-phenyl/benzyl substituent greatly affects the biological activity.
• 8-Phenylxanthines displayed potent activity in comparison to 8-benzyl analogs.

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 A2A receptors and also produced potent bronchospasmolytic effects. Replacement of phenyl ring with benzyl moiety at C8 of xanthine skeleton resulted in notable reduction in adenosine receptor affinity and broncholytic effects.

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.Figure optionsDownload as PowerPoint slide