Synthesis and biological evaluation of novel compounds within a class of 3-aminochroman derivatives with dual 5-HT1A receptor and serotonin transporter affinity.
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.
Hatzenbuhler
Nicole T
NT
Chemical and Screening Sciences and Discovery Neuroscience, Wyeth Research, CN 8000, Princeton, New Jersey 08543, USA. hatzenn@wyeth.com
Evrard
Deborah A
DA
Harrison
Boyd L
BL
Huryn
Donna
D
Inghrim
Jennifer
J
Kraml
Christina
C
Mattes
James F
JF
Mewshaw
Richard E
RE
Zhou
Dahui
D
Hornby
Geoffrey
G
Lin
Qian
Q
Smith
Deborah L
DL
Sullivan
Kelly M
KM
Schechter
Lee E
LE
Beyer
Chad E
CE
Andree
Terrance H
TH
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
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