Synthesis, Pharmacology and Molecular Modeling of N-Substituted 2-Phenyl-indoles and Benzimidazoles as Potent GABAA Agonists.

Abstract Among the known non-benzodiazepine hypnotic drugs, Zolpidem ( 1a ), Indiplon ( 2a ) and Zaleplon ( 2b ) have shown high affinity and selectivity for the α 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 α 1 receptor and potent in vivo induction of sedation.