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

Bioorg Med Chem Lett. 2003 Mar 10;13(5):817-20. doi: 10.1016/s0960-894x(03)00027-1.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / chemistry*
  • Adenosine / metabolism*
  • Animals
  • CHO Cells
  • Cricetinae
  • Drug Design
  • Hydrocarbons, Fluorinated / chemical synthesis*
  • Hydrocarbons, Fluorinated / metabolism*
  • Kinetics
  • Ligands
  • Protein Binding
  • Purinergic P1 Receptor Agonists
  • Radioligand Assay
  • Rats
  • Receptor, Adenosine A3
  • Receptors, Purinergic P1 / metabolism*
  • Recombinant Proteins / agonists
  • Recombinant Proteins / metabolism
  • Structure-Activity Relationship


  • Hydrocarbons, Fluorinated
  • Ligands
  • Purinergic P1 Receptor Agonists
  • Receptor, Adenosine A3
  • Receptors, Purinergic P1
  • Recombinant Proteins
  • Adenosine
  • 2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide