Synthesis of new opioid derivatives with a propellane skeleton and their pharmacology: part 1

Bioorg Med Chem Lett. 2011 Jul 1;21(13):4104-7. doi: 10.1016/j.bmcl.2011.04.147. Epub 2011 May 10.

Abstract

The observation that 17-cyclopropylmethylmorphinan derivatives without the 4,5-epoxy ring showed more κ selectivity than those with a 4,5-epoxy ring led us to develop a working hypothesis: the position of the plane composed of the A and B rings would influence the opioid receptor type selectivity and that the decrease in the torsion angle C11-C12-C13-C14 could improve the κ selectivity. Consistent with our hypothesis, KNT-42 with an N-cyclopropylmethyl propellane structure, whose A and B rings were fixed in a torsion angle of approximately 0°, showed κ selective agonist activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / chemical synthesis*
  • Analgesics, Opioid / chemistry
  • Analgesics, Opioid / pharmacology*
  • Animals
  • Bridged-Ring Compounds / chemical synthesis*
  • Bridged-Ring Compounds / chemistry
  • Bridged-Ring Compounds / pharmacology*
  • Cells, Cultured
  • Mice
  • Molecular Structure
  • Protein Binding / drug effects
  • Receptors, Opioid, kappa / metabolism*
  • Structure-Activity Relationship
  • Substrate Specificity

Substances

  • Analgesics, Opioid
  • Bridged-Ring Compounds
  • KNT 42
  • Receptors, Opioid, kappa