Design, synthesis and binding affinity of 3′-fluoro analogues of Cl-IB-MECA as adenosine A₃ receptor ligands

Several 3′-fluoro analogues, 1a, 1b, and 1c of selective and potent adenosine A₃ receptor agonist, Cl-IB-MECA were synthesized from D-xylose via highly regioselective opening of lyxo-epoxides, 8a and 8b with fluoride anion. Compared to the high binding affinity of Cl-IB-MECA to the A₃ adenosine receptor, the corresponding 3′-fluoro derivative showed remarkably decreased binding affinity, indicating that 3′-hydroxyl group acts as hydrogen bonding acceptor, not hydrogen bonding donor like fluorine atom in binding to the A₃ adenosine receptor.