Enantiomeric (-)-(1R,5R,9R) and (+)-(1S,5S,9S) heterocyclic N-substituted-normetazocines: Synthesis of potent and selective antinociceptives and opioid antagonists through N-substituent modification

E. L. May, M. D. Aceto, E. R. Bowman, J. R. Traynor, J. H. Woods, A. E. Jacobson, L. S. Harris

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

A number of diverse N-substituted-N-normetazocine heterocycles ((-)-1R,5R,9R)- and (+)-(1S,5S,9S)-5,9-dimethyl-2′-hydroxy-2-substituted-6,7-benzomorphans) were synthesized and evaluated. Conversion of an antinociceptively inactive alcohol to an ether (-)-1R,5R,9R)-5,9-dimethyl-2′-hydroxy-2-(2-methoxyethyl)-6,7-benzomorph an ((-)-N-methoxyethylnormetazocine, 4), gave a compound that was 10 to 40 times more potent than morphine as an antinociceptive agent, but did not attenuate morphine withdrawal in monkeys. Other (-)-enantiomers also had potent antinociceptive activity and one, (-)-N-fluoropropylnormetazocine (9), was a potent opioid antagonist.

Original languageEnglish (US)
Pages (from-to)178-185
Number of pages8
JournalMedicinal Chemistry Research
Volume10
Issue number3
StatePublished - Dec 1 2000
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

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