A bivalent ligand (KMN-21) antagonist for mu/kappa heterodimeric opioid receptors

Bioorg Med Chem Lett. 2009 Dec 15;19(24):6978-80. doi: 10.1016/j.bmcl.2009.10.045. Epub 2009 Nov 4.

Abstract

In an effort to develop antagonists for kappa-mu opioid receptor heterodimers, a series of bivalent ligands 3-6 containing kappa- and mu-antagonist pharmacophores were designed and synthesized. Evaluation of the series in HEK-293 cells revealed 4 (KMN-21) to selectively antagonize the activation of kappa-mu heterodimers, suggesting possible bridging of receptors when the bivalent ligand spacer contains 21 atoms.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Line
  • Guanidines / chemical synthesis
  • Guanidines / chemistry*
  • Guanidines / pharmacology
  • Humans
  • Ligands
  • Naltrexone / analogs & derivatives*
  • Naltrexone / chemical synthesis
  • Naltrexone / chemistry
  • Naltrexone / pharmacology
  • Receptors, Opioid, kappa / antagonists & inhibitors*
  • Receptors, Opioid, mu / antagonists & inhibitors*

Substances

  • Guanidines
  • KMN-21 compound
  • Ligands
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • Naltrexone