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.