The use of a pharmacophore model for identification of novel ligands for the benzodiazepine binding site of the GABAA receptor

Synthesis and biological evaluation of flavan-3-ol derivatives as positive modulators of GABAA receptors

“…(E)-2 0 -Hydroxy-4-methoxychalcone (1) and a number of substituted analogues (2)(3)(4)(5)(6)(7)(8)(9) were prepared by the base catalysed condensation of the appropriately substituted acetophenones and benzaldehdes. The chalcones were reduced to the unprotected (E)-1,3-diarylpropenes (10)(11)(12)(13)(14)(15)(16)(17)(18) as previously reported for 10; 20 via protection of the 2 0 -hydroxy function, subsequent reduction with NaBH 4 and finally treatment with dilute acid (Scheme 1). While this reduction frequently afforded small yields of both the over-reduced product and the positional ene isomer, these could be removed by a combination of preparative chromatography and recrystallisation.…”

“…However, these studies have been based on the results of ligand-binding assays on brain tissue, which includes a mixture of receptor subtypes that have different binding affinities for benzodiazepines. 11,12,[16][17][18] The present study characterises the structure-activity of a series of relatively simple flavan-3-ol derivatives in a functional assay using human recombinant a 1 b 2 c 2L GABA A receptors expressed in Xenopus laevis oocytes.…”

3D-QSAR studies of 4-quinolone derivatives as high-affinity ligands at the benzodiazepine site of brain GABAA receptors

“…Lager and co workers synthesized a series of 4-quinolone derivatives comprising total 29 compounds through optimization of the 4-quinolone lead identified by 3D database search (using pharmacophore model for the benzodiazepine receptor) (Kahnberg et al, 2004;Erik et al 2006). …”

Structural basis for ligand recognition at the benzodiazepine binding site of GABAA α3 receptor, and pharmacophore-based virtual screening approach

“…g-Amino butyric acid (GABA), the principal inhibitory neurotransmitter in the mammalian central nervous system exerts its physiological effects by binding to three major classes of receptors, namely GABA A , GABA B and GABA C [1]. The GABA A receptor, along with nicotinic acetylcholine receptor (nAChR), glycine receptor (GlyR) and 5-hydroxytryptamine (5-HT3) receptor, belongs to Cysloop super family of ligand-gated ion channels (LGIC) [2].…”