Syntheses of novel high affinity ligands for opioid receptors

Bioorg Med Chem Lett. 2009 Apr 15;19(8):2289-94. doi: 10.1016/j.bmcl.2009.02.078. Epub 2009 Feb 25.


A series of novel high affinity opioid receptor ligands have been made whereby the phenolic-OH group of nalbuphine, naltrexone methiodide, 6-desoxonaltrexone, hydromorphone and naltrindole was replaced by a carboxamido group and the furan ring was opened to the corresponding 4-OH derivatives. These furan ring 'open' derivatives display very high affinity for mu and kappa receptors and much less affinity for delta. The observation that these target compounds have much higher receptor affinity than the corresponding ring 'closed' carboxamides significantly strengthens our underlying pharmacophore hypothesis concerning the bioactive conformation of the carboxamide group.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Analgesics, Opioid / chemical synthesis*
  • Analgesics, Opioid / metabolism
  • Crystallography, X-Ray
  • Furans / chemical synthesis
  • Furans / metabolism
  • Humans
  • Ligands
  • Naltrexone / chemical synthesis
  • Naltrexone / metabolism
  • Narcotic Antagonists / chemical synthesis*
  • Narcotic Antagonists / metabolism
  • Protein Binding
  • Receptors, Opioid / agonists
  • Receptors, Opioid / metabolism*


  • Analgesics, Opioid
  • Furans
  • Ligands
  • Narcotic Antagonists
  • Receptors, Opioid
  • Naltrexone