Synthesis of quinolinomorphinan derivatives as highly selective δ opioid receptor ligands

Bioorg Med Chem. 2012 Oct 1;20(19):5810-31. doi: 10.1016/j.bmc.2012.08.004. Epub 2012 Aug 11.

Abstract

We have reported previously the novel δ opioid agonist KNT-127 which showed high affinity and selectivity for the δ receptor. Moreover, the analgesic effect of subcutaneously administered KNT-127 was more potent than that of a prototypical δ agonist (-)-TAN-67 in the acetic acid writhing test. This study of the structure-activity relationship of KNT-127 derivatives focused on the introduction of substituents onto the 5'-, 6'-, 7'- or 8'-position of the quinoline ring and revealed that many derivatives with 5'- or 8'-substituents showed high affinities and selectivities for the δ receptor. Especially, SYK-153 with an 8'-OH group showed the highest affinity and the most balanced and highest selectivity for the δ receptor among the synthesized compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / chemical synthesis
  • Analgesics / chemistry*
  • Analgesics / pharmacology*
  • Animals
  • Mice
  • Morphinans / chemical synthesis
  • Morphinans / chemistry*
  • Morphinans / pharmacology*
  • Quinolines / chemical synthesis
  • Quinolines / chemistry*
  • Quinolines / pharmacology*
  • Receptors, Opioid, delta / agonists*
  • Receptors, Opioid, delta / metabolism
  • Structure-Activity Relationship
  • Swine

Substances

  • Analgesics
  • KNT 127
  • Morphinans
  • Quinolines
  • Receptors, Opioid, delta