Access to 7β-analogs of codeine with mixed μ/δ agonist activity via 6,7-α-epoxide opening

Bioorg Med Chem Lett. 2013 Sep 1;23(17):4870-4. doi: 10.1016/j.bmcl.2013.06.084. Epub 2013 Jul 4.

Abstract

(-)-Codeine 1 was converted into previously unknown 7β-methyl-7,8-dihydrocodeine/morphine derivatives such as 13 via classical diaxial opening of α-epoxide 3. Several analogs exhibited dual μ/δ-agonist activity.

Keywords: 6,7-α-Epoxide; Metopon; Mixed μ/δ agonist; Opioid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Codeine / analogs & derivatives*
  • Codeine / pharmacology*
  • Epoxy Compounds / chemistry
  • Epoxy Compounds / pharmacology
  • Humans
  • Mice
  • Models, Molecular
  • Morphinans / chemistry
  • Morphinans / pharmacology
  • Receptors, Opioid, delta / agonists*
  • Receptors, Opioid, delta / metabolism
  • Receptors, Opioid, mu / agonists*
  • Receptors, Opioid, mu / metabolism

Substances

  • Epoxy Compounds
  • Morphinans
  • Receptors, Opioid, delta
  • Receptors, Opioid, mu
  • metopon
  • Codeine