Novel 6β-acylaminomorphinans with analgesic activity

András Váradi, Sándor Hosztafi, Valerie Le Rouzic, Gergo Tóth, Ákos Urai, Béla Noszál, Gavril W. Pasternak, Steven G. Grinnell, Susruta Majumdar

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)786-789
Number of pages4
JournalEuropean Journal of Medicinal Chemistry
Volume69
DOIs
Publication statusPublished - 2013

Keywords

  • Aminomorphinan
  • Analgesia
  • Cinnamoyl morphinamine
  • MOR/DOR agonist
  • Opioid
  • Respiratory depression

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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  • Cite this

    Váradi, A., Hosztafi, S., Le Rouzic, V., Tóth, G., Urai, Á., Noszál, B., Pasternak, G. W., Grinnell, S. G., & Majumdar, S. (2013). Novel 6β-acylaminomorphinans with analgesic activity. European Journal of Medicinal Chemistry, 69, 786-789. https://doi.org/10.1016/j.ejmech.2013.09.031