Structure-activity relationship studies of carboxamido-biaryl ethers as opioid receptor antagonists (OpRAs). Part 1

Bioorg Med Chem Lett. 2007 Oct 1;17(19):5349-52. doi: 10.1016/j.bmcl.2007.08.008. Epub 2007 Aug 11.

Abstract

A structurally unique and new class of opioid receptor antagonists (OpRAs) that bear no structural resemblance with morphine or endogenous opioid peptides has been discovered. A series of carboxamido-biaryl ethers were identified as potent receptor antagonists against mu, kappa and delta opioid receptors. The structure-activity relationship indicated para-substituted aryloxyaryl primary carboxamide bearing an amine tether on the distal phenyl ring was optimal for potent in vitro functional antagonism against three opioid receptor subtypes.

MeSH terms

  • Animals
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Drug Design
  • Ethers / chemical synthesis*
  • Ethers / pharmacology*
  • Guanosine 5'-O-(3-Thiotriphosphate) / antagonists & inhibitors
  • Humans
  • Molecular Conformation
  • Narcotic Antagonists*
  • Receptors, Opioid, delta / antagonists & inhibitors
  • Receptors, Opioid, kappa / antagonists & inhibitors
  • Receptors, Opioid, mu / antagonists & inhibitors
  • Structure-Activity Relationship

Substances

  • Ethers
  • Narcotic Antagonists
  • Receptors, Opioid, delta
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • Guanosine 5'-O-(3-Thiotriphosphate)