title: Tetrahydrocarbazole-based serotonin reuptake inhibitor/dopamine D2 partial agonists for the potential treatment of schizophrenia.
abstract: A 5-fluoro-tetrahydrocarbazole serotonin reuptake inhibitor (SRI) building block was combined with a variety of linkers and dopamine D2 receptor ligands in an attempt to identify potent D2 partial agonist/SRI molecules for treatment of schizophrenia. This approach has the potential to treat a broader range of symptoms compared to existing therapies. Selected compounds in this series demonstrate high affinity for both targets and D2 partial agonism in cell-based and in vivo assays.
authors.affiliation: Chemical Sciences, Wyeth Research, CN 8000 Princeton, NJ 08543, United States. rotelld@wyeth.com
authors.forename: David P
authors.initials: DP
authors.lastname: Rotella
authors.forename: Geraldine R
authors.initials: GR
authors.lastname: McFarlane
authors.forename: Alexander
authors.initials: A
authors.lastname: Greenfield
authors.forename: Cristina
authors.initials: C
authors.lastname: Grosanu
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Robichaud
authors.forename: Rajiah Aldrin
authors.initials: RA
authors.lastname: Denny
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Feenstra
authors.forename: Sara
authors.initials: S
authors.lastname: Núñez-García
authors.forename: Jan-Hendrik
authors.initials: JH
authors.lastname: Reinders
authors.forename: Martina van der
authors.initials: Mv
authors.lastname: Neut
authors.forename: Andrew
authors.initials: A
authors.lastname: McCreary
authors.forename: Chris G
authors.initials: CG
authors.lastname: Kruse
authors.forename: Kelly
authors.initials: K
authors.lastname: Sullivan
authors.forename: Farhana
authors.initials: F
authors.lastname: Pruthi
authors.forename: Margaret
authors.initials: M
authors.lastname: Lai
authors.forename: Jean
authors.initials: J
authors.lastname: Zhang
authors.forename: Dianne M
authors.initials: DM
authors.lastname: Kowal
authors.forename: Tikva
authors.initials: T
authors.lastname: Carrick
authors.forename: Steven M
authors.initials: SM
authors.lastname: Grauer
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Navarra
authors.forename: Radka
authors.initials: R
authors.lastname: Graf
authors.forename: Julie
authors.initials: J
authors.lastname: Brennan
authors.forename: Karen L
authors.initials: KL
authors.lastname: Marquis
authors.forename: Mark H
authors.initials: MH
authors.lastname: Pausch
mesh_terms: D000818:Animals; D002227:Carbazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy*; D058829:Serotonin 5-HT1 Receptor Antagonists; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D002227:Carbazoles; D018491:Dopamine Agonists; D044282:Receptor, Serotonin, 5-HT1A; D017448:Receptors, Dopamine D2; D058829:Serotonin 5-HT1 Receptor Antagonists; D017367:Selective Serotonin Reuptake Inhibitors