Novel trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines as mu opioid receptor antagonists with improved opioid receptor selectivity profiles

Bioorg Med Chem Lett. 2008 Mar 15;18(6):2006-12. doi: 10.1016/j.bmcl.2008.01.106. Epub 2008 Feb 2.

Abstract

A series of N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines, mu opioid receptor antagonists, analogs of alvimopan, were prepared using solid phase methodology. This study led to the identification of a highly selective mu opioid receptor antagonist, which interacts selectively with mu peripheral receptors.

MeSH terms

  • Administration, Oral
  • Animals
  • Cell Membrane / metabolism
  • Central Nervous System / drug effects*
  • Chromatography, High Pressure Liquid
  • Diprenorphine / metabolism
  • Gastrointestinal Transit / drug effects
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Humans
  • Loperamide / pharmacology
  • Mice
  • Molecular Structure
  • Piperidines / chemical synthesis
  • Piperidines / chemistry*
  • Piperidines / pharmacology*
  • Receptors, Opioid, delta / antagonists & inhibitors*
  • Receptors, Opioid, delta / metabolism
  • Receptors, Opioid, kappa / antagonists & inhibitors*
  • Receptors, Opioid, kappa / metabolism
  • Receptors, Opioid, mu / antagonists & inhibitors*
  • Receptors, Opioid, mu / metabolism
  • Structure-Activity Relationship

Substances

  • OPRM1 protein, human
  • Piperidines
  • Receptors, Opioid, delta
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • Diprenorphine
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • alvimopan
  • Loperamide