Effects of substituent size upon adenosine receptor A1/A2 affinity of some newly synthesised 8-cycloalkyl xanthines.
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.
Castagnino
E
E
Institute of Medicinal Chemistry, University of Urbino, Italy.
Salvatori
A
A
Corsano
S
S
Tacchi
P
P
Martini
C
C
Lucacchini
A
A
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*
D008024:Ligands; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014970:Xanthines; C046489:1,3-dipropylxanthine