Synthesis, pharmacology and molecular modeling of N-substituted 2-phenyl-indoles and benzimidazoles as potent GABA(A) agonists

Eur J Med Chem. 2006 Aug;41(8):985-90. doi: 10.1016/j.ejmech.2006.03.031. Epub 2006 Jun 9.


Among the known non-benzodiazepine hypnotic drugs, Zolpidem (1a), Indiplon (2a) and Zaleplon (2b) have shown high affinity and selectivity for the alpha(1) subunit of the GABA-A receptor. Our group has performed pharmacophoric and ADMET-prediction studies to evaluate a virtual library of new molecules based on privileged structures. Among these, we have synthesized a library of N-substituted indoles and a library of N-substituted benzimidazoles. Afterwards, in vitro screening and in vivo spontaneous motor activity in mice has revealed molecules with good in vitro affinities for the alpha(1) receptor and potent in vivo induction of sedation.

MeSH terms

  • Benzimidazoles / chemical synthesis
  • Benzimidazoles / chemistry*
  • Benzimidazoles / pharmacology*
  • Drug Evaluation, Preclinical
  • GABA-A Receptor Agonists*
  • Indoles / chemical synthesis
  • Indoles / chemistry*
  • Indoles / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Models, Molecular*


  • Benzimidazoles
  • GABA-A Receptor Agonists
  • Indoles