3-(2-Ethoxy-4-{4-[3-hydroxy-2-methyl-4-(3-methylbutanoyl)phenoxy]butoxy}phenyl)propanoic acid: a brain penetrant allosteric potentiator at the metabotropic glutamate receptor 2 (mGluR2)

Bioorg Med Chem Lett. 2005 May 2;15(9):2389-93. doi: 10.1016/j.bmcl.2005.02.078.

Abstract

We have identified and synthesized a brain penetrant propanoic acid as an allosteric potentiator of the metabotropic glutamate receptor 2. Structure-activity relationship studies directed toward improving the potency, level of potentiation and brain penetration led to the discovery of 8 (EC50=1200 nM, 77% potentiation, 119% brain/plasma in rat, 20 mpk i.p., brain level of 5700 nM).

MeSH terms

  • Allosteric Regulation
  • Animals
  • Brain / drug effects
  • Brain / physiology*
  • Butanes / chemical synthesis*
  • Butanes / pharmacokinetics
  • Butanes / pharmacology*
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Kinetics
  • Molecular Conformation
  • Phenyl Ethers
  • Propionates / chemical synthesis*
  • Propionates / pharmacokinetics
  • Propionates / pharmacology*
  • Rats
  • Receptors, Metabotropic Glutamate / drug effects
  • Receptors, Metabotropic Glutamate / physiology*
  • Structure-Activity Relationship

Substances

  • 3-(2-ethoxy-4-(4-(3-hydroxy-2-methyl-4-(3-methylbutanoyl)phenoxy)butoxy)phenyl)propanoic acid
  • Butanes
  • Phenyl Ethers
  • Propionates
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 2
  • Guanosine 5'-O-(3-Thiotriphosphate)