Synthesis and pharmacological evaluation of hydrophobic esters and ethers of butorphanol at opioid receptors

Bioorg Med Chem Lett. 2008 Aug 15;18(16):4474-6. doi: 10.1016/j.bmcl.2008.07.054. Epub 2008 Jul 17.


We synthesized several hydrophobic esters and ethers of butorphanol and assessed their affinities at opioid receptors in CHO cell membranes. Tested compounds displayed moderate to high affinities to the mu and kappa receptors. The findings accord with previous evidence of a lipophilic binding pocket in the opioid receptors that can be accessed to afford good binding affinity without the need for a phenolic hydrogen-bond donor group. The most potent (K(i)=61 pM at mu and 48 pM at kappa) novel agent was (-)-N-cyclobutylmethylmorphinan-3-yl-14-ol phenoxyacetate (4d).

Publication types

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

MeSH terms

  • Animals
  • Butorphanol / chemical synthesis*
  • Butorphanol / chemistry*
  • CHO Cells
  • Chemistry, Pharmaceutical / methods*
  • Cricetinae
  • Cricetulus
  • Drug Design
  • Hydrophobic and Hydrophilic Interactions
  • Kinetics
  • Models, Chemical
  • Narcotic Antagonists*
  • Phenol
  • Protein Binding
  • Receptors, Opioid / chemistry*
  • Temperature


  • Narcotic Antagonists
  • Receptors, Opioid
  • Phenol
  • Butorphanol