title: Clozapine derived 2,3-dihydro-1H-1,4- and 1,5-benzodiazepines with D4 receptor selectivity: synthesis and biological testing.
abstract: Novel 4-arylpiperazin-1-yl-substituted 2,3-dihydro-1H-1,4- and 1H-1,5-benzodiazepines and their aza-analogues were synthesized as debenzoclozapine derivatives for evaluation as potential D4-ligands. While Ki values of some of the title compounds came within the range of clozapine, they showed an impressively greater selectivity over other dopamine receptor subtypes, especially D2. For the most promising compounds, intrinsic activity and binding properties to serotonin 5-HT1A and 5-HT2 were also determined.
authors.affiliation: Department of Medicinal Chemistry, Emil Fischer Center, Friedrich-Alexander University, Schuhstrasse 19, D-91052 Erlangen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hussenether
authors.forename: Harald
authors.initials: H
authors.lastname: Hübner
authors.forename: Peter
authors.initials: P
authors.lastname: Gmeiner
authors.forename: Reinhard
authors.initials: R
authors.lastname: Troschütz
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001667:Binding, Competitive; D016466:CHO Cells; D003024:Clozapine / Q000031:analogs & derivatives*; D006224:Cricetinae; D003412:Cricetulus; D065127:Dopamine D2 Receptor Antagonists; D006801:Humans; D015394:Molecular Structure; D050638:Receptors, Dopamine D4; D058829:Serotonin 5-HT1 Receptor Antagonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D013552:Swine
chemical_list: C493599:DRD4 protein, human; D065127:Dopamine D2 Receptor Antagonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D001569:Benzodiazepines; D050638:Receptors, Dopamine D4; D003024:Clozapine