Synthesis and preliminary in vitro investigation of bivalent ligands containing homo- and heterodimeric pharmacophores at mu, delta, and kappa opioid receptors.
Article Details
- CitationCopy to clipboard
Peng X, Knapp BI, Bidlack JM, Neumeyer JL
Synthesis and preliminary in vitro investigation of bivalent ligands containing homo- and heterodimeric pharmacophores at mu, delta, and kappa opioid receptors.
J Med Chem. 2006 Jan 12;49(1):256-62.
- PubMed ID
- 16392810 [ View in PubMed]
- Abstract
A series of homo- and heterodimeric ligands containing kappa agonist and mu agonist/antagonist pharmacophores joined by a linker chain of varying lengths was synthesized and evaluated in vitro by their binding affinity at mu, delta, and kappa opioid receptors. The functional activities of these compounds were measured in the [(35)S]GTPgammaS binding assay. The data suggest that the stereochemistry of the pharmacophores, the N-substituents of the pharmacophore, ester linkages, and the spacer length were crucial factors for optimum interactions of such ligands at opioid receptor binding sites. These novel ligands as well as their pharmacological properties will serve as the basis for our continuing investigation of such bivalent ligands as probes of the opioid receptor oligomerization phenomena and for in vivo studies as analgesics.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Levorphanol Kappa-type opioid receptor Ki (nM) 2.3 N/A N/A Details Levorphanol Mu-type opioid receptor Ki (nM) 0.21 N/A N/A Details Morphine Kappa-type opioid receptor Ki (nM) 24 N/A N/A Details Morphine Mu-type opioid receptor Ki (nM) 0.88 N/A N/A Details