Design, synthesis and biological evaluation of a bivalent micro opiate and adenosine A1 receptor antagonist

Bioorg Med Chem Lett. 2009 Dec 1;19(23):6736-9. doi: 10.1016/j.bmcl.2009.09.112. Epub 2009 Oct 3.

Abstract

The cross talk between different membrane receptors is the source of increasing research. We designed and synthesized a new hetero-bivalent ligand that has antagonist properties on both A(1) adenosine and mu opiate receptors with a K(i) of 0.8+/-0.05 and 0.7+/-0.03 microM, respectively. This hybrid molecule increases cAMP production in cells that over express the mu receptor as well as those over expressing the A(1) adenosine receptor and reverses the antalgic effects of mu and A(1) adenosine receptor agonists in animals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / chemical synthesis
  • Adenosine / chemistry
  • Adenosine / pharmacology
  • Adenosine A1 Receptor Antagonists*
  • Anilides / chemical synthesis
  • Anilides / chemistry
  • Anilides / pharmacology*
  • Drug Design*
  • Ligands
  • Molecular Structure
  • Receptors, Opioid, mu / antagonists & inhibitors*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Adenosine A1 Receptor Antagonists
  • Anilides
  • Ligands
  • Receptors, Opioid, mu
  • Adenosine