Ribose-modified adenosine analogues as adenosine receptor agonists.
Analogues of the potent adenosine receptor agonist (R)-N-(1-methyl-2-phenylethyl)adenosine (R-PIA), modified at N9, were prepared and evaluated for adenosine A1 and A2 receptor binding and in vivo central nervous system and cardiovascular effects. The modifications at N9 include deoxy sugars, 5'-substituted-5'-deoxyriboses, non-ribose sugars, sugar ring homologues, and acyclic sugar analogues. Most of the derivatives have poor affinity for adenosine receptors. Only minor modifications at C5' and C3' maintain potent binding. In general, those derivatives exhibiting in vivo behavioral or cardiovascular effects also have the highest affinity for adenosine receptors.
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011983:Receptors, Purinergic; D012266:Ribose; D013329:Structure-Activity Relationship
D011956:Receptors, Cell Surface; D011983:Receptors, Purinergic; C027513:N(6)-cyclohexyladenosine; D012266:Ribose; D000241:Adenosine