Imidazo[1,2-a]pyrimidines as functionally selective and orally bioavailable GABA(A)alpha2/alpha3 binding site agonists for the treatment of anxiety disorders

J Med Chem. 2006 Jan 12;49(1):35-8. doi: 10.1021/jm051065l.


A series of high-affinity GABA(A) agonists with good oral bioavailability in rat and dog and functional selectivity for the GABA(A)alpha2 and -alpha3 subtypes is reported. The 7-trifluoromethylimidazopyrimidine 14g and the 7-propan-2-olimidazopyrimidine 14k are anxiolytic in both conditioned and unconditioned animal models of anxiety with minimal sedation observed at full BZ binding site occupancy.

MeSH terms

  • Administration, Oral
  • Animals
  • Anxiety Disorders / drug therapy*
  • Binding Sites
  • Biological Availability
  • Cell Line
  • Disease Models, Animal
  • Dogs
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • GABA-A Receptor Agonists*
  • Humans
  • Molecular Structure
  • Patch-Clamp Techniques
  • Pyrimidines / chemical synthesis
  • Pyrimidines / pharmacokinetics
  • Pyrimidines / pharmacology*
  • Rats
  • Receptors, GABA-A
  • Structure-Activity Relationship


  • GABA-A Receptor Agonists
  • GABRA3 protein, human
  • Gabra3 protein, rat
  • Pyrimidines
  • Receptors, GABA-A