Structure-activity relationships in a series of 8-substituted xanthines as A1-adenosine receptor antagonists.
A series of 8-substituted xanthines were synthesized and their affinity in vitro towards A1, A2A-adenosine receptors was evaluated by radioligand receptor binding assays. All compounds showed a greater affinity and selectivity towards the A1-adenosine receptor than theophylline. The compounds in which the n-proyl group is in 1-position of the xanthine nucleus and the pyridazinone system in 8-position is linked through a chain of two or four carbon atoms, showed the highest affinity and selectivity.
Strappaghetti
G
G
Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia, Italy. noemi@unipg.it
Corsano
S
S
Barbaro
R
R
Giannaccini
G
G
Betti
L
L
D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000648:ultrastructure; D003342:Corpus Striatum / Q000166:cytology / Q000648:ultrastructure; D058915:Purinergic P1 Receptor Antagonists; D011869:Radioligand Assay; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D013329:Structure-Activity Relationship; D013806:Theophylline / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D014970:Xanthines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014970:Xanthines; D013806:Theophylline