In an effort to develop antagonists for κ-μ opioid receptor heterodimers, a series of bivalent ligands 3-6 containing κ- and μ-antagonist pharmacophores were designed and synthesized. Evaluation of the series in HEK-293 cells revealed 4 (KMN-21) to selectively antagonize the activation of κ-μ heterodimers, suggesting possible bridging of receptors when the bivalent ligand spacer contains 21 atoms.
Bibliographical noteFunding Information:
We thank Mike Powers for capable technical assistance. This research is supported by grant DA01533 from National Institute on Drug Abuse .
Copyright 2010 Elsevier B.V., All rights reserved.
- Bivalent ligand
- Opioid receptors