Discovery of the first N-substituted 4beta-methyl-5-(3-hydroxyphenyl)morphan to possess highly potent and selective opioid delta receptor antagonist activity

J Med Chem. 2004 Jan 15;47(2):281-4. doi: 10.1021/jm030419a.

Abstract

A structurally novel opioid delta receptor selective antagonist has been identified. This compound, (+)-5-(3-hydroxyphenyl)-4-methyl-2-(3-phenylpropyl)-2-azabicyclo[3.3.1]non-7-yl-(1-phenyl-1-cyclopentane)carboxamide [(+)-KF4, (+)-4], showed a K(e) value of 0.15 nM in the [(35)S]GTPgammaS functional assay. (+)-KF4 is also a delta inverse agonist with an IC(50) value of 1.8 nM. To our knowledge, this is the first potent and selective delta opioid receptor antagonist from the 5-phenylmorphan class of opioids.

Publication types

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

MeSH terms

  • Animals
  • Binding, Competitive
  • Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis*
  • Bridged Bicyclo Compounds, Heterocyclic / chemistry
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • CHO Cells
  • Cricetinae
  • Humans
  • Radioligand Assay
  • Receptors, Opioid, delta / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • 5-(3-hydroxyphenyl)-4-methyl-2-(3-phenylpropyl)-2-azabicyclo(3.3.1)non-7-yl-(1-phenyl-1-cyclopentane)carboxamide
  • Bridged Bicyclo Compounds, Heterocyclic
  • Receptors, Opioid, delta