title: Synthesis and biological evaluation of novel compounds within a class of 3-aminochroman derivatives with dual 5-HT1A receptor and serotonin transporter affinity.
abstract: Compounds containing a 5-carbamoyl-8-fluoro-3-amino-3,4-dihydro-2H-1-benzopyran and a 3-alkylindole moiety linked through a common basic nitrogen were prepared and evaluated for 5-HT1A affinity, serotonin rat transporter affinity, and functional antagonist activity in vitro. 26a was found to be the most potent and selective compound in this series and was shown to possess neurochemical activity in vivo by producing acute and rapid increases in 5-HT in the rat frontal cortex.
authors.affiliation: Chemical and Screening Sciences and Discovery Neuroscience, Wyeth Research, CN 8000, Princeton, New Jersey 08543, USA. hatzenn@wyeth.com
authors.forename: Nicole T
authors.initials: NT
authors.lastname: Hatzenbuhler
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Evrard
authors.forename: Boyd L
authors.initials: BL
authors.lastname: Harrison
authors.forename: Donna
authors.initials: D
authors.lastname: Huryn
authors.forename: Jennifer
authors.initials: J
authors.lastname: Inghrim
authors.forename: Christina
authors.initials: C
authors.lastname: Kraml
authors.forename: James F
authors.initials: JF
authors.lastname: Mattes
authors.forename: Richard E
authors.initials: RE
authors.lastname: Mewshaw
authors.forename: Dahui
authors.initials: D
authors.lastname: Zhou
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Hornby
authors.forename: Qian
authors.initials: Q
authors.lastname: Lin
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Smith
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Sullivan
authors.forename: Lee E
authors.initials: LE
authors.lastname: Schechter
authors.forename: Chad E
authors.initials: CE
authors.lastname: Beyer
authors.forename: Terrance H
authors.initials: TH
authors.lastname: Andree
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016466:CHO Cells; D002839:Chromans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017551:Microdialysis; D011869:Radioligand Assay; D051381:Rats; D012701:Serotonin / Q000096:biosynthesis; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000928:Antidepressive Agents; D001578:Benzopyrans; D002839:Chromans; D007211:Indoles; D012701:Serotonin; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C513011:3-(cyclobutyl(3-(5-fluoro-1H-indol-3-yl)propyl)amino)-8-fluorochromane-5-carboxamide