title: Novel 8-(p-substituted-phenyl/benzyl)xanthines with selectivity for the A2A adenosine receptor possess bronchospasmolytic activity.
abstract: 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.
authors.affiliation: University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Yadav
authors.affiliation: University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India. Electronic address: ranju29in@yahoo.co.in.
authors.forename: Ranju
authors.initials: R
authors.lastname: Bansal
authors.affiliation: Institut für Pharmakologie und Toxikologie, Universität Würzburg, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Kachler
authors.affiliation: Institut für Pharmakologie und Toxikologie, Universität Würzburg, Germany.
authors.forename: K N
authors.initials: KN
authors.lastname: Klotz
mesh_terms: D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D001993:Bronchodilator Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D016466:CHO Cells; D003412:Cricetulus; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D011485:Protein Binding; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D014970:Xanthines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D001993:Bronchodilator Agents; D043705:Receptor, Adenosine A2A; D014970:Xanthines
keywords: 8-Phenylxanthines; Adenosine receptors; Bronchospasmolytic activity