Synthesis and pharmacological evaluation of 4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalenyl amines as triple reuptake inhibitors

The present work describes a series of novel chiral amines that potently inhibit the in vitro reuptake of serotonin, norepinephrine and dopamine (triple reuptake inhibitors) and were active in vivo in a mouse model predictive of antidepressant like activity. The detailed synthesis and in vitro activ...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2011-01, Vol.19 (1), p.663-676
Main Authors: Shao, Liming, Wang, Fengjiang, Malcolm, Scott C., Ma, Jianguo, Hewitt, Michael C., Campbell, Una C., Bush, Larry R., Spicer, Nancy A., Engel, Sharon R., Saraswat, Lakshmi D., Hardy, Larry W., Koch, Patrick, Schreiber, Rudy, Spear, Kerry L., Varney, Mark A.
Format: Article
Language:English
Subjects:
animal models
Animals
Antidepressant
antidepressants
Antidepressive Agents - chemical synthesis
Antidepressive Agents - pharmacology
Biological and medical sciences
chemistry
chemotypes
Depression
Disease Models, Animal
dopamine
Dopamine - metabolism
Drug Evaluation, Preclinical
Medical sciences
Mice
Monoamine transporter
Naphthalenes - chemical synthesis
Naphthalenes - pharmacology
Neuropharmacology
Neurotransmitter Uptake Inhibitors - chemical synthesis
Neurotransmitter Uptake Inhibitors - pharmacology
norepinephrine
Norepinephrine - metabolism
Pharmacology. Drug treatments
Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer
Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)
Psychology. Psychoanalysis. Psychiatry
Psychopharmacology
serotonin
Serotonin - metabolism
Triple uptake inhibitor (TRI)
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Summary:The present work describes a series of novel chiral amines that potently inhibit the in vitro reuptake of serotonin, norepinephrine and dopamine (triple reuptake inhibitors) and were active in vivo in a mouse model predictive of antidepressant like activity. The detailed synthesis and in vitro activity and ADME profile of compounds is described, which represent a previously undisclosed triple reuptake inhibitor chemotype.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2010.10.034