Ring-Constrained (N)-methanocarba nucleosides as adenosine receptor agonists: independent 5'-uronamide and 2'-deoxy modifications

Bioorg Med Chem Lett. 2001 May 21;11(10):1333-7. doi: 10.1016/s0960-894x(01)00213-x.

Abstract

Novel methanocarba adenosine analogues, having the pseudo-ribose northern (N) conformation preferred at adenosine receptors (ARs), were synthesized and tested in binding assays. The 5'-uronamide modification preserved [N6-(3-iodobenzyl)] or enhanced (N6-methyl) affinity at A3ARs, while the 2'-deoxy modification reduced affinity and efficacy in a functional assay.

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / chemical synthesis*
  • Adenine / metabolism
  • Adenine / pharmacology
  • Adenosine / analogs & derivatives*
  • Adenosine / chemical synthesis*
  • Adenosine / metabolism
  • Adenosine / pharmacology
  • Animals
  • Binding, Competitive
  • Brain / ultrastructure
  • CHO Cells
  • Cell Line
  • Cell Membrane / chemistry
  • Cricetinae
  • Cyclopentanes / chemical synthesis*
  • Cyclopentanes / metabolism
  • Cyclopentanes / pharmacology
  • Humans
  • Nucleosides / pharmacology*
  • Protein Binding
  • Purinergic P1 Receptor Agonists*
  • Rats
  • Receptors, Purinergic P1 / metabolism
  • Structure-Activity Relationship
  • Transfection

Substances

  • Cyclopentanes
  • Nucleosides
  • Purinergic P1 Receptor Agonists
  • Receptors, Purinergic P1
  • carbocyclic deoxyadenosine
  • aristeromycin
  • Adenine
  • Adenosine