Ring-Constrained (N)-methanocarba nucleosides as adenosine receptor agonists: independent 5'-uronamide and 2'-deoxy modifications.
Novel methanocarba adenosine analogues, having the pseudo-ribose northern (N) conformation preferred at adenosine receptors (ARs), were synthesized and tested in binding assays. The 5'-uronamide modification preserved [N6-(3-iodobenzyl)] or enhanced (N6-methyl) affinity at A3ARs, while the 2'-deoxy modification reduced affinity and efficacy in a functional assay.
Lee
K
K
Molecular Recognition Section, LBC, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.
Ravi
G
G
Ji
X D
XD
Marquez
V E
VE
Jacobson
K A
KA
D000225:Adenine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000648:ultrastructure; D016466:CHO Cells; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry; D006224:Cricetinae; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D009705:Nucleosides / Q000494:pharmacology*; D011485:Protein Binding; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D013329:Structure-Activity Relationship; D014162:Transfection
D003517:Cyclopentanes; D009705:Nucleosides; D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1; C113082:carbocyclic deoxyadenosine; C030034:aristeromycin; D000225:Adenine; D000241:Adenosine