Document Detail


Structural exploration of (3S,6S)-6-benzhydryl-N-benzyltetrahydro-2H-pyran-3-amine analogues: identification of potent triple monoamine reuptake inhibitors as potential antidepressants.
MedLine Citation:
PMID:  23060293     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
To further explore the basic structural motifs (3S,6S)-6-benzhydryl-N-benzyltetrahydro-2H-pyran-3-amine and (2S,4R,5R)-2-benzhydryl-5-(benzylamino)tetrahydro-2H-pyran-4-ol, developed by our research group, for monoamine transport inhibition, we designed and synthesized various structurally altered analogues. The new compounds were tested for their affinities for the dopamine transporter (DAT), the serotonin transporter (SERT), and the norepinephrine transporter (NET) in rat brain by measuring their capacity to inhibit the uptake of [(3)H]DA, [(3)H]5-HT, and [(3)H]NE, respectively. Our results point to novel compounds with a TUI, DNRI, SNRI, or SSRI profile. Among the TUIs, compound 2 g exhibited a balanced potency for all three monoamine transporters (K(i): 60, 79, and 70.3 nM for DAT, SERT, and NET, respectively). In the rat forced swim test, compound 2 g produced a significant decrease in immobility in drug-treated rats relative to vehicle, indicating a potential antidepressant property.
Authors:
Soumava Santra; Sanjib Gogoi; Bhaskar Gopishetty; Tamara Antonio; Juan Zhen; Maarten E A Reith; Aloke K Dutta
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-10-11
Journal Detail:
Title:  ChemMedChem     Volume:  7     ISSN:  1860-7187     ISO Abbreviation:  ChemMedChem     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-27     Completed Date:  2013-04-29     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  101259013     Medline TA:  ChemMedChem     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  2093-100     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antidepressive Agents / chemistry*,  pharmacology*
Brain / drug effects,  metabolism
Dopamine Plasma Membrane Transport Proteins / antagonists & inhibitors,  metabolism
Male
Motor Activity / drug effects
Neurotransmitter Uptake Inhibitors / chemistry*,  pharmacology*
Norepinephrine / metabolism
Norepinephrine Plasma Membrane Transport Proteins / antagonists & inhibitors,  metabolism
Pyrans / chemistry*,  pharmacology*
Rats
Rats, Sprague-Dawley
Serotonin / metabolism
Serotonin Plasma Membrane Transport Proteins / metabolism
Grant Support
ID/Acronym/Agency:
MH084888/MH/NIMH NIH HHS; R01 MH084888/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Antidepressive Agents; 0/Dopamine Plasma Membrane Transport Proteins; 0/Neurotransmitter Uptake Inhibitors; 0/Norepinephrine Plasma Membrane Transport Proteins; 0/Pyrans; 0/Serotonin Plasma Membrane Transport Proteins; 333DO1RDJY/Serotonin; X4W3ENH1CV/Norepinephrine
Comments/Corrections

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