title: 6-[2-(4-Aryl-1-piperazinyl)ethyl]-2H-1,4-benzoxazin-3(4H)-ones: dual-acting 5-HT1 receptor antagonists and serotonin reuptake inhibitors.
abstract: Investigation of a series 6-[2-(4-aryl-1-piperazinyl)ethyl]-2H-1,4-benzoxazin-3(4H)-ones has led to the discovery of potent 5-HT(1A/1B/1D) receptor antagonists with and without additional SerT affinity. Modulation of the different target activities gave compounds with a range of profiles suitable for further in vivo characterization.
authors.affiliation: Neurosciences CEDD, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK. steve.bromidge@gsk.com
authors.forename: Steven M
authors.initials: SM
authors.lastname: Bromidge
authors.forename: Barbara
authors.initials: B
authors.lastname: Bertani
authors.forename: Manuela
authors.initials: M
authors.lastname: Borriello
authors.forename: Stefania
authors.initials: S
authors.lastname: Faedo
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Gordon
authors.forename: Enrica
authors.initials: E
authors.lastname: Granci
authors.forename: Matthew
authors.initials: M
authors.lastname: Hill
authors.forename: Howard R
authors.initials: HR
authors.lastname: Marshall
authors.forename: Luigi P
authors.initials: LP
authors.lastname: Stasi
authors.forename: Valeria
authors.initials: V
authors.lastname: Zucchelli
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Merlo
authors.forename: Alessia
authors.initials: A
authors.lastname: Vesentini
authors.forename: Jeannette M
authors.initials: JM
authors.lastname: Watson
authors.forename: Laura
authors.initials: L
authors.lastname: Zonzini
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001583:Benzoxazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008956:Models, Chemical; D000077489:Piperazine; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000928:Antidepressive Agents; D001583:Benzoxazoles; D000077489:Piperazine; D010879:Piperazines; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors