Analgesics and narcotic antagonists in the benzomorphan and 8-oxamorphinan series. 5

J Med Chem. 1978 May;21(5):423-7. doi: 10.1021/jm00203a003.

Abstract

3-Methoxy-8-oxamorphinans 9 have been prepared from the corresponding 5-allyl-9alpha-hydroxy-2'-methoxy-2-methyl-6,7-benzomorphans 7. The former compounds were transformed to the 3-hydroxy-8-oxamorphinans 6, a class of potent analgesics and analgesic-antagonists. In ring C of the morphinan nucleus substitution of 8-CH2 with oxygen enhanced both analgesic and antagonist activities, while replacement of hydrogen with a methyl group at C-14 in these compounds enhanced antagonist activity and decreased analgesic activity. Tetrahydrofuranobenzomorphans 3 and 3-hydroxy-8-oxaisomorphinans 4 displayed lower levels of activity. Structural requirements for antagonist activity are discussed.

MeSH terms

  • Analgesics / chemical synthesis*
  • Animals
  • Benzomorphans / analogs & derivatives
  • Benzomorphans / chemical synthesis*
  • Benzomorphans / pharmacology
  • Mice
  • Morphinans / chemical synthesis*
  • Morphinans / pharmacology
  • Narcotic Antagonists / chemical synthesis*
  • Structure-Activity Relationship

Substances

  • Analgesics
  • Benzomorphans
  • Morphinans
  • Narcotic Antagonists