Synthesis and binding affinity of novel mono- and bivalent morphinan ligands for kappa, mu, and delta opioid receptors.
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Zhang B, Zhang T, Sromek AW, Scrimale T, Bidlack JM, Neumeyer JL
Synthesis and binding affinity of novel mono- and bivalent morphinan ligands for kappa, mu, and delta opioid receptors.
Bioorg Med Chem. 2011 May 1;19(9):2808-16. doi: 10.1016/j.bmc.2011.03.052. Epub 2011 Mar 26.
- PubMed ID
- 21482470 [ View in PubMed]
- Abstract
A novel series of homo- and heterodimeric ligands containing kappa/mu agonist and mu agonist/antagonist pharmacophores joined by a 10-carbon ester linker chain were synthesized and evaluated for their in vitro binding affinity at kappa, mu, and delta opioid receptors, and their functional activities were determined at kappa and mu receptors in [(35)S]GTPgammaS functional assays. Most of these compounds had high binding affinity at mu and kappa receptors (K(i) values less than 1nM). Compound 15b, which contains butorphan (1) at one end of linking chain and butorphanol (5) at the other end, was the most potent ligand in this series with binding affinity K(i) values of 0.089nM at the mu receptor and 0.073nM at the kappa receptor. All of the morphinan-derived ligands were found to be partial kappa and mu agonists; ATPM-derived ligands 12 and 11 were found to be full kappa agonists and partial mu agonists.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Butorphanol Kappa-type opioid receptor Ki (nM) 0.12 N/A N/A Details Butorphanol Mu-type opioid receptor Ki (nM) 0.22 N/A N/A Details Naloxone Kappa-type opioid receptor Ki (nM) 0.25 N/A N/A Details Naloxone Mu-type opioid receptor Ki (nM) 0.23 N/A N/A Details