Synthesis of novel triplet drugs with 1,3,5-trioxazatriquinane skeletons and their pharmacologies. 1: Synthesis of triplet drugs with morphinan skeletons

Bioorg Med Chem Lett. 2011 Jul 1;21(13):4023-6. doi: 10.1016/j.bmcl.2011.04.134. Epub 2011 May 5.


We synthesized symmetrical and nonsymmetrical triplet drugs with 1,3,5-trioxazatriquinane skeletons. The isolation of key intermediates, oxazoline dimers, made it possible to effectively produce nonsymmetrical triplets. Among the synthesized triplets, KNT-93, composed of three identical opioid μ receptor agonists, showed dose-dependent antinociception via the μ receptor. The effect was 56-fold more potent than that of morphine, a representative μ agonist. The profound analgesic effect induced by KNT-93 might result from simultaneous occupation of three μ opioid receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / chemical synthesis*
  • Analgesics / chemistry
  • Bridged-Ring Compounds / chemical synthesis*
  • Bridged-Ring Compounds / chemistry
  • Dose-Response Relationship, Drug
  • Molecular Structure
  • Morphinans / chemistry*
  • Naltrexone / analogs & derivatives*
  • Naltrexone / chemical synthesis
  • Naltrexone / chemistry
  • Receptors, Opioid, mu / agonists


  • Analgesics
  • Bridged-Ring Compounds
  • KNT 93
  • Morphinans
  • Receptors, Opioid, mu
  • Naltrexone