Investigation of phenolic bioisosterism in opiates: 3-sulfonamido analogues of naltrexone and oxymorphone

Org Lett. 2000 Mar 23;2(6):819-21. doi: 10.1021/ol005561+.

Abstract

[formula: see text] The phenolic hydroxy group of opiate-derived ligands is of known importance for biological activity. On the basis of its putative role as a hydrogen-bonding donor in the interaction with opioid receptors, it was replaced with a sulfonamide group because of their similar pKa values. The first thebaine-derived 3-amino (8a, 8b) and subsequent sulfonamide analogues (10a, 10b) were synthesized from naltrexone (1a) and oxymorphone (1b) in a linear nine-step synthesis. The sulfonamides were tested in vitro and found inactive.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Indicators and Reagents
  • Models, Molecular
  • Molecular Conformation
  • Naltrexone / analogs & derivatives*
  • Naltrexone / chemical synthesis
  • Naltrexone / chemistry*
  • Narcotics / chemical synthesis
  • Narcotics / chemistry*
  • Oxymorphone / analogs & derivatives*
  • Oxymorphone / chemical synthesis
  • Oxymorphone / chemistry*
  • Stereoisomerism
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry*

Substances

  • Indicators and Reagents
  • Narcotics
  • Sulfonamides
  • Naltrexone
  • Oxymorphone