Novel 6β-acylaminomorphinans with analgesic activity

Eur J Med Chem. 2013 Nov;69:786-9. doi: 10.1016/j.ejmech.2013.09.031. Epub 2013 Sep 22.


Aminomorphinans are a relatively young class of opioid drugs among which substances of high in vitro efficacy and favorable in vivo action are found. We report the synthesis and pharmacological evaluation of novel 6β-acylaminomorphinans. 6β-Morphinamine and 6β-codeinamine were stereoselectively synthesized by Mitsunobu reaction. The aminomorphinans were subsequently acylated with diversely substituted cinnamic acids. In vitro binding studies on cinnamoyl morphinamines showed moderate affinity for all opiate receptors with some selectivity for mu opioid receptors, while cinnamoyl codeinamines only showed affinity for mu opioid receptors. In vivo analgesia studies showed significant analgesic activity of 6β-cinnamoylmorphinamine mediated by mu and delta receptors. The lead compound was found to be roughly equipotent to morphine (ED₅₀ 3.13 ± 1.09 mg/kg) but devoid of the dangerous side-effect respiratory depression, a major issue associated with traditional opioid therapy.

Keywords: Aminomorphinan; Analgesia; Cinnamoyl morphinamine; MOR/DOR agonist; Opioid; Respiratory depression.

Publication types

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

MeSH terms

  • Analgesics / chemical synthesis
  • Analgesics / chemistry
  • Analgesics / pharmacology*
  • Animals
  • Dose-Response Relationship, Drug
  • Hot Temperature
  • Mice
  • Molecular Structure
  • Morphinans / chemical synthesis
  • Morphinans / chemistry
  • Morphinans / pharmacology*
  • Morphine / adverse effects
  • Morphine / pharmacology
  • Narcotic Antagonists
  • Pain Measurement
  • Pain Threshold / drug effects*
  • Receptors, Opioid / agonists
  • Respiratory Insufficiency / chemically induced
  • Structure-Activity Relationship
  • Time Factors


  • 6-cinnamoylmorphinamine
  • Analgesics
  • Morphinans
  • Narcotic Antagonists
  • Receptors, Opioid
  • Morphine