Design, synthesis, and biological evaluation of LNA nucleosides as adenosine A3 receptor ligands

Bioorg Med Chem. 2007 Aug 15;15(16):5440-7. doi: 10.1016/j.bmc.2007.05.056. Epub 2007 May 26.

Abstract

We have prepared a series of adenosine analogs based on the bicyclo[2.2.1]heptane scaffold of locked nucleic acid (LNA) and tested them for both agonist and antagonist activity at the adenosine A(3) receptor. The design of these derivatives was based on the known A(3) agonist IB-MECA and related compounds. Modifications thus include the 5'-uronamides and N(6)-(3-iodobenzyl) derivatives. In this way we have prepared analogs of known A(3) agonists with the sugar ring restricted in an N-conformation. For comparison we have also prepared 2'-O-methyl derivatives of IB-MECA. The LNA nucleosides showed no agonist activity but some of them are potent antagonists. The 2'-O-methyl derivative of IB-MECA is an agonist with similar potency as the parent compound.

MeSH terms

  • Adenosine A3 Receptor Agonists
  • Cell Line
  • Drug Design*
  • Humans
  • Inhibitory Concentration 50
  • Ligands
  • Molecular Structure
  • Nucleic Acids / chemistry*
  • Nucleosides / chemical synthesis
  • Nucleosides / chemistry*
  • Nucleosides / pharmacology*
  • Receptor, Adenosine A3 / metabolism*

Substances

  • Adenosine A3 Receptor Agonists
  • Ligands
  • Nucleic Acids
  • Nucleosides
  • Receptor, Adenosine A3