Discovery of Peripheral κ-Opioid Receptor Agonists as Novel Analgesics

Chem Pharm Bull (Tokyo). 2017;65(11):1085-1088. doi: 10.1248/cpb.c17-00555.

Abstract

κ-Opioid receptor agonists with high selectivity over the μ-opioid receptor and peripheral selectivity are attractive targets in the development of drugs for pain. We have previously attempted to create novel analgesics with peripheral selective κ-opioid receptor agonist on the basis of TRK-820. In this study, we elucidated the biological properties of 17-hydroxy-cyclopropylmethyl and 10α-hydroxy derivatives. These compounds were found to have better κ-opioid receptor selectivity and peripheral selectivity than TRK-820.

Keywords: TRK-820; analgesic; κ-opioid receptor; μ-opioid receptor.

MeSH terms

  • Acetic Acid
  • Analgesics / chemical synthesis
  • Analgesics / chemistry
  • Analgesics / pharmacology*
  • Animals
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Models, Molecular
  • Molecular Conformation
  • Morphinans / chemical synthesis
  • Morphinans / chemistry
  • Morphinans / pharmacology*
  • Pain / chemically induced
  • Pain / drug therapy*
  • Receptors, Opioid, kappa / agonists*
  • Spiro Compounds / chemical synthesis
  • Spiro Compounds / chemistry
  • Spiro Compounds / pharmacology*
  • Structure-Activity Relationship

Substances

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