title: Effects of substituent size upon adenosine receptor A1/A2 affinity of some newly synthesised 8-cycloalkyl xanthines.
abstract: The activity of a series of 1,3-dipropyl-xanthines bearing C8-cycloalkyl substituents as antagonists at A1 and A2 adenosine receptors is examined. Pharmacological results showed that the size of the 8-substituent is an important feature for response in activity of such class of antagonists. Among compounds 3-8, the 2-norbornyl analog 6 showed the best A1/A2 selectivity. A new route for the synthesis of 8-alkyl-substituted xanthines is presented. This method, consisting of a direct alkylation of the imidazole moiety through a radical mechanism reaction, was shown to be a more convenient strategy in comparison with the commonly employed synthetic schemes.
authors.affiliation: Institute of Medicinal Chemistry, University of Urbino, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Castagnino
authors.forename: A
authors.initials: A
authors.lastname: Salvatori
authors.forename: S
authors.initials: S
authors.lastname: Corsano
authors.forename: P
authors.initials: P
authors.lastname: Tacchi
authors.forename: C
authors.initials: C
authors.lastname: Martini
authors.forename: A
authors.initials: A
authors.lastname: Lucacchini
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D017072:Neostriatum / Q000378:metabolism; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D012756:Sheep; D013329:Structure-Activity Relationship; D014970:Xanthines / Q000138:chemical synthesis* / Q000378:metabolism*
chemical_list: D008024:Ligands; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014970:Xanthines; C046489:1,3-dipropylxanthine