title: A structural study of new potent and selective antagonists to the A2B adenosine receptor.
abstract: Xanthines, including the natural derivatives theophylline and caffeine, are non-selective antagonists of adenosine. They are able to bind with good affinity to all four adenosine-receptor subtypes A1, A2A, A2B and A3. In order to develop new drugs with few side effects, over the last few years many efforts have been devoted to the discovery of new adenosine antagonists with enhanced selectivity properties. The present paper reports the crystal structures of five new xanthinic derivatives, which display different affinities and selectivity properties towards the A2B receptor. Besides the crystallographic study, a structural comparison has been made with the calculated geometry of other xanthinic derivatives which are reported to have similar biological characteristics to understand the structural features controlling their affinity capabilities and selectivity. This structural comparison has been interpreted in the light of a recently published study on the binding of N-benzo[1,3]-dioxol-5-yl-2-[5-(2,6-dioxo-1,3-dipropyl-2,3,6,9-tetrahydro-1H-purin-8-yl)-1-methyl-1-H-pyrazol-3-iloxy]-acetamide to a model of the A2B receptor, which shows the most interesting affinity and selectivity properties.
authors.affiliation: Dipartimento di Chimica and Centro di Strutturistica Diffrattometrica, University of Ferrara, via L. Borsari 46, I-44100 Ferrara, Italy. frt@unife.it
authors.forename: Valeria
authors.initials: V
authors.lastname: Ferretti
authors.forename: Loretta
authors.initials: L
authors.lastname: Pretto
authors.forename: Mojgan Aghazadeh
authors.initials: MA
authors.lastname: Tabrizi
authors.forename: Valerio
authors.initials: V
authors.lastname: Bertolasi
mesh_terms: D000081:Acetamides / Q000737:chemistry; D000241:Adenosine / Q000737:chemistry; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D001216:Asparagine / Q000737:chemistry; D002110:Caffeine / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D018360:Crystallography, X-Ray / Q000379:methods; D015195:Drug Design; D006639:Histidine / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D007700:Kinetics; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D013806:Theophylline / Q000494:pharmacology; D014970:Xanthines / Q000737:chemistry
chemical_list: D000081:Acetamides; D058917:Adenosine A2 Receptor Antagonists; D008024:Ligands; D014970:Xanthines; D002110:Caffeine; D006639:Histidine; D001216:Asparagine; D013806:Theophylline; D000241:Adenosine