Ethers of 3-hydroxyphenylacetic acid as selective gamma-hydroxybutyric acid receptor ligands

Bioorg Med Chem Lett. 2005 Jul 1;15(13):3201-2. doi: 10.1016/j.bmcl.2005.05.011.

Abstract

Gamma-hydroxybutyric acid (GHB) is a drug of abuse, a therapeutic, and purportedly a neurotransmitter with a complex mechanism of action in vivo due to direct actions at GABA(B) as well as GHB receptors and because of its metabolism to GABA. Herein, we describe 3-ethers of 3-hydroxyphenylacetic acid, which have relatively high affinity at GHB sites, no significant affinity at GABA receptors, and would not be expected to be rapidly metabolized to GABAergic ligands. The selectivity of these compounds (UMB108, UMB109, and UMB119) could prove to be useful for studying the biology of GHB receptors, free from GABAergic effects.

Publication types

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

MeSH terms

  • Animals
  • Cell Membrane / chemistry
  • Cerebellum / cytology
  • Cerebral Cortex / cytology
  • Ethers
  • Inhibitory Concentration 50
  • Ligands
  • Phenylacetates / chemical synthesis
  • Phenylacetates / chemistry*
  • Radioligand Assay
  • Rats
  • Receptors, Cell Surface / chemistry*
  • Structure-Activity Relationship

Substances

  • 3-hydroxyphenylacetate
  • 4-hydroxybutyric acid receptor
  • Ethers
  • Ligands
  • Phenylacetates
  • Receptors, Cell Surface