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...

Full description

Saved in:
Bibliographic Details
Published in:Journal of medicinal chemistry 2006-07, Vol.49 (15), p.4785-4789
Main Authors: Hatzenbuhler, Nicole T, Evrard, Deborah A, Harrison, Boyd L, Huryn, Donna, Inghrim, Jennifer, Kraml, Christina, Mattes, James F, Mewshaw, Richard E, Zhou, Dahui, Hornby, Geoffrey, Lin, Qian, Smith, Deborah L, Sullivan, Kelly M, Schechter, Lee E, Beyer, Chad E, Andree, Terrance H
Format: Article
Language:English
Subjects:
Animals
Antidepressive Agents - chemical synthesis
Antidepressive Agents - chemistry
Antidepressive Agents - pharmacology
Benzopyrans - chemical synthesis
Benzopyrans - chemistry
Benzopyrans - pharmacology
Biological and medical sciences
CHO Cells
Chromans - chemical synthesis
Chromans - chemistry
Chromans - pharmacology
Cricetinae
Cricetulus
Frontal Lobe - drug effects
Frontal Lobe - metabolism
Humans
Indoles - chemical synthesis
Indoles - chemistry
Indoles - pharmacology
Medical sciences
Microdialysis
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Pharmacology. Drug treatments
Radioligand Assay
Rats
Serotonin - biosynthesis
Serotonin 5-HT1 Receptor Agonists
Serotonin 5-HT1 Receptor Antagonists
Serotonin Plasma Membrane Transport Proteins - metabolism
Serotonin Uptake Inhibitors - chemical synthesis
Serotonin Uptake Inhibitors - chemistry
Serotonin Uptake Inhibitors - pharmacology
Serotoninergic system
Stereoisomerism
Structure-Activity Relationship
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm060218h