Design, synthesis, and structure-activity relationship of novel opioid kappa-agonists

Bioorg Med Chem. 2008 Oct 15;16(20):9188-201. doi: 10.1016/j.bmc.2008.09.011. Epub 2008 Sep 9.

Abstract

By focusing on 4,5-epoxymorphinan, a traditional opioid skeleton but a new structure in the opioid kappa-agonist research field, and by rationally applying the 'message-address concept' and 'accessory site hypothesis,' we discovered a new chemical class opioid kappa-agonist, TRK-820 (1). Its development as an antipruritus is now in the final stage. Here, the full scope of its design, synthesis, and structure-activity relationship are described.

MeSH terms

  • Analgesics, Opioid / chemical synthesis
  • Analgesics, Opioid / chemistry
  • Drug Design*
  • Molecular Structure
  • Morphinans / chemical synthesis
  • Morphinans / chemistry
  • Morphinans / pharmacology
  • Receptors, Opioid, kappa / agonists*
  • Receptors, Opioid, kappa / antagonists & inhibitors
  • Receptors, Opioid, kappa / metabolism
  • Spiro Compounds / chemical synthesis
  • Spiro Compounds / chemistry
  • Spiro Compounds / pharmacology
  • Structure-Activity Relationship

Substances

  • Analgesics, Opioid
  • Morphinans
  • Receptors, Opioid, kappa
  • Spiro Compounds
  • TRK 820