title: Conformational analysis and pharmacophore design for selected 1-(2-pyrimidinyl)piperazine derivatives with sedative-hypnotic activity.
abstract: The conformational of selected 1-(2-pyrimidinyl)piperazine derivatives with high sedative-hypnotic activity was analysed and the model bioactive conformations were suggested. Subsequently, the pharmacophores of analysed compounds were designed. It was suggested that the pharmacophore of bioactive derivatives should be composed of 11 features that characterise the binding model of pyrimidinylpiperazine ligands to the binding site at the hypothetic receptor. This 11 feature pharmacophore was compared to three other pharmacophores designed for the selected anxiolytics (benzodiazepines and buspirone analogues) and the sedative-hypnotic agents (benzodiazepines and barbiturates). Several substantial differences between the pharmacophores were found: the number of pharmacophoric features and their distribution in 3-D space were unique for selected groups of compounds that exhibit sedative-hypnotic or anxiolytic activity.
authors.affiliation: Department of Chemistry, University of Warsaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Bronowska
authors.forename: A
authors.initials: A
authors.lastname: Leś
authors.forename: M
authors.initials: M
authors.lastname: Mazgajska
authors.forename: Z
authors.initials: Z
authors.lastname: Chilmończyk
mesh_terms: D006993:Hypnotics and Sedatives / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D008968:Molecular Conformation; D010879:Piperazines / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D006993:Hypnotics and Sedatives; D010879:Piperazines