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

Abstract Several 3′-fluoro analogues, 1a , 1b , and 1c of selective and potent adenosine A 3 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 A 3 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 A 3 adenosine receptor.