title: Novel imidazobenzazepine derivatives as dual H1/5-HT2A antagonists for the treatment of sleep disorders.
abstract: A novel imidazobenzazepine template (5a) with potent dual H(1)/5-HT(2A) antagonist activity was identified. Application of a zwitterionic approach to this poorly selective and poorly developable starting point successfully delivered a class of high quality leads, 3-[4-(3-R(1)-2-R-5H-imidazo[1,2-b][2]benzazepin-11-yl)-1-piperazinyl]-2,2-dimethylpropanoic acids (e.g., 9, 19, 20, and 21), characterized by potent and balanced H(1)/5-HT(2A) receptor antagonist activities and good developability profiles.
authors.affiliation: Neurosciences CEDD, GlaxoSmithKline, Medicines Research Centre, Verona, Italy. massimo.gianotti@aptuit.com
authors.forename: Massimo
authors.initials: M
authors.lastname: Gianotti
authors.forename: Corrado
authors.initials: C
authors.lastname: Corti
authors.forename: Sonia
authors.initials: S
authors.lastname: Delle Fratte
authors.forename: Romano
authors.initials: R
authors.lastname: Di Fabio
authors.forename: Colin P
authors.initials: CP
authors.lastname: Leslie
authors.forename: Francesca
authors.initials: F
authors.lastname: Pavone
authors.forename: Laura
authors.initials: L
authors.lastname: Piccoli
authors.forename: Luigi
authors.initials: L
authors.lastname: Stasi
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Wigglesworth
mesh_terms: D006801:Humans; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects*; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D012893:Sleep Wake Disorders / Q000188:drug therapy*
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A