title: Synthesis, pharmacology and molecular modeling of N-substituted 2-phenyl-indoles and benzimidazoles as potent GABA(A) agonists.
abstract: 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.
authors.affiliation: Medicinal Chemistry Department, R and D Center, Ferrer Internacional S.A., Juan de Sada 32, E-08028 Barcelona, Spain. jlfalco-research@ferrergrupo.com
authors.forename: José Luis
authors.initials: JL
authors.lastname: Falcó
authors.forename: Maria
authors.initials: M
authors.lastname: Piqué
authors.forename: Miguel
authors.initials: M
authors.lastname: González
authors.forename: Irma
authors.initials: I
authors.lastname: Buira
authors.forename: Eva
authors.initials: E
authors.lastname: Méndez
authors.forename: Jose
authors.initials: J
authors.lastname: Terencio
authors.forename: Cristina
authors.initials: C
authors.lastname: Pérez
authors.forename: Marta
authors.initials: M
authors.lastname: Príncep
authors.forename: Albert
authors.initials: A
authors.lastname: Palomer
authors.forename: Antonio
authors.initials: A
authors.lastname: Guglietta
mesh_terms: D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D058785:GABA-A Receptor Agonists; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular
chemical_list: D001562:Benzimidazoles; D058785:GABA-A Receptor Agonists; D007211:Indoles