Abstract
This study explored the impact of structural modifications on truncated 4'-selenonucleosides as ligands for the A(3) adenosine receptor (AR). We synthesized and evaluated a series of these compounds for their binding affinities, functional activities, and structural interactions by using computational modeling. The SAR study revealed that all compounds exhibited selective and notable hA(3)AR binding, among which 6l (K (i) = 5.2 nM) and 6m (K (i) = 5.7 nM) were found as the best binding compounds. The representative N (6)-cyclopropyl compound 6m was found to be a partial agonist, contrasting with the antagonist profiles of truncated 4'-oxo and 4'-thionucleosides. Computational docking highlighted 6m's unique interaction with Thr94 at the A(3)AR binding site. This research not only advances our understanding of A(3)AR ligand interactions but also highlights the potential of truncated 4'-selenonucleosides as effective A(3)AR modulators.