Deoxymorphines: role of the phenolic hydroxyl in antinociception and opiate receptor interactions

J Med Chem. 1979 Mar;22(3):256-9. doi: 10.1021/jm00189a007.

Abstract

Several 3-deoxy opioids and 3,6-dideoxydihydromorphine was synthesized to ascertain the effect of the phenolic hydroxyl group on antinociceptive potency and receptor binding affinity. Catalytic reduction of the 3-tetrazolyl ether derivatives of dihydromorphine provided the entry into the 3-deoxydihydro series. The prototype, 3-deoxymorphine, was prepared by lithium aluminum hydride reduction of 3-deoxy-N-carbethoxymorphinone, obtained via its 7-(phenylseleno) derivative. 3-Deoxydihydromorphinone and 3,6-dideoxydihydromorphine were found to be about as potent as, or more potent than, morphine in standard antiociceptive assays. Each of them, however, was less potent than the comparable 3-hydroxy analogue, and their binding affinity to the opiate receptor was substantially decreased. The epoxy ring in 3.6-dideoxydihydromorphine was found to increase the antinociceptive potency of the compound.

MeSH terms

  • Analgesics*
  • Animals
  • Chemical Phenomena
  • Chemistry
  • Mice
  • Morphine Derivatives / chemical synthesis
  • Morphine Derivatives / pharmacology*
  • Receptors, Opioid / drug effects*
  • Structure-Activity Relationship

Substances

  • Analgesics
  • Morphine Derivatives
  • Receptors, Opioid