Structure-activity relationships of truncated D- and l-4'-thioadenosine derivatives as species-independent A3 adenosine receptor antagonists

J Med Chem. 2008 Oct 23;51(20):6609-13. doi: 10.1021/jm8008647. Epub 2008 Sep 24.

Abstract

Novel D- and l-4'-thioadenosine derivatives lacking the 4'-hydroxymethyl moiety were synthesized, starting from d-mannose and d-gulonic gamma-lactone, respectively, as potent and selective species-independent A 3 adenosine receptor (AR) antagonists. Among the novel 4'-truncated 2-H nucleosides tested, a N(6)-(3-chlorobenzyl) derivative 7c was the most potent at the human A 3 AR (K i = 1.5 nM), but a N(6)-(3-bromobenzyl) derivative 7d showed the optimal species-independent binding affinity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / chemical synthesis
  • Adenosine / chemistry
  • Adenosine / pharmacology
  • Adenosine A3 Receptor Antagonists*
  • Animals
  • Humans
  • Molecular Structure
  • Rats
  • Receptor, Adenosine A3 / metabolism
  • Structure-Activity Relationship
  • Thionucleosides / chemical synthesis*
  • Thionucleosides / chemistry
  • Thionucleosides / pharmacology*

Substances

  • Adenosine A3 Receptor Antagonists
  • Receptor, Adenosine A3
  • Thionucleosides
  • 4'-thioadenosine
  • Adenosine