A diastereoselective synthesis of Cebranopadol, a novel analgesic showing NOP/mu mixed agonism

Sci Rep. 2017 May 25;7(1):2416. doi: 10.1038/s41598-017-02502-9.

Abstract

A diastereoselective synthesis of the title compound as a single E diastereomer has been efficiently accomplished by assembling the featured pyrano-indole scaffold of the spiro[cyclohexane-dihydropyrano[3,4-b]-indole]-amine framework through an oxa-Pictet-Spengler reaction, promoted by a cheap and green Zeolite catalyst. Basic pharmacological experiments demonstrate that Cebranopadol acts as a mixed nociception/orphanin FQ (NOP) and mu (MOP) opioid receptor agonist useful for treatment of chronic pain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / chemical synthesis*
  • Analgesics / chemistry
  • Analgesics / pharmacology*
  • Chemistry Techniques, Synthetic
  • Chromatography, Liquid
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Mass Spectrometry
  • Nociceptin Receptor
  • Receptors, Opioid / agonists*
  • Receptors, Opioid, mu / agonists*
  • Spiro Compounds / chemical synthesis*
  • Spiro Compounds / chemistry
  • Spiro Compounds / pharmacology*

Substances

  • 6'-fluoro-4',9'-dihydro-N,N-dimethyl-4-phenylspiro(cyclohexane-1,1'(3'H)-pyrano(3,4-b)indol)-4-amine
  • Analgesics
  • Indoles
  • Receptors, Opioid
  • Receptors, Opioid, mu
  • Spiro Compounds
  • Nociceptin Receptor