Development of imidazole alkanoic acids as mGAT3 selective GABA uptake inhibitors

Eur J Med Chem. 2011 May;46(5):1483-98. doi: 10.1016/j.ejmech.2011.01.042. Epub 2011 Feb 3.


A new series of potential GABA uptake inhibitors starting from of 1H-imidazol-4-ylacetic acid with the carboxylic acid side chain originating from different positions and varying in length have been synthesized and tested for the inhibitory potency at the four GABA uptake transporters mGAT1-4 stably expressed in HEK cells. Further two bicyclic compounds with a rigidified carboxylic acid side chain were included in this study. The results of the biological tests indicated that most ω-imidazole alkanoic and alkenoic acid derivatives exhibit the highest potencies as GABA uptake inhibitors at mGAT3.

MeSH terms

  • Cell Line
  • GABA Plasma Membrane Transport Proteins / chemistry
  • GABA Plasma Membrane Transport Proteins / metabolism*
  • GABA Uptake Inhibitors / chemical synthesis
  • GABA Uptake Inhibitors / chemistry
  • GABA Uptake Inhibitors / pharmacology*
  • Humans
  • Imidazoles / chemical synthesis
  • Imidazoles / chemistry
  • Imidazoles / pharmacology*
  • Molecular Structure
  • Stereoisomerism
  • Structure-Activity Relationship
  • Substrate Specificity


  • 1H-imidazol-4-ylacetic acid
  • GABA Plasma Membrane Transport Proteins
  • GABA Uptake Inhibitors
  • Imidazoles