Exploration of substituted arylpiperazine–tetrazoles as promising dual norepinephrine and dopamine reuptake inhibitors

[Display omitted] In the search for potent dual norepinephrine and dopamine reuptake inhibitors, several substituted arylpiperazine–tetrazoles were designed, synthesized and evaluated for their neurotransmitter reuptake inhibitory activities. Various derivatives exhibited selective and strong neurot...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2016-11, Vol.24 (21), p.5546-5555
Main Authors: Paudel, Suresh, Acharya, Srijan, Yoon, Goo, Kim, Kyeong-Man, Cheon, Seung Hoon
Format: Article
Language:English
Subjects:
Arylpiperazine–tetrazoles
Dopamine - metabolism
Dopamine reuptake inhibitors
Dose-Response Relationship, Drug
HEK293 Cells
Humans
Molecular Structure
Norepinephrine - antagonists & inhibitors
Norepinephrine - metabolism
Norepinephrine reuptake inhibitors
Piperazines - chemical synthesis
Piperazines - chemistry
Piperazines - pharmacology
Selective norepinephrine and dopamine reuptake inhibitors
Structure-Activity Relationship
Tetrazoles - chemical synthesis
Tetrazoles - chemistry
Tetrazoles - pharmacology
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Summary:[Display omitted] In the search for potent dual norepinephrine and dopamine reuptake inhibitors, several substituted arylpiperazine–tetrazoles were designed, synthesized and evaluated for their neurotransmitter reuptake inhibitory activities. Various derivatives exhibited selective and strong neurotransmitter reuptake inhibitory activity. In particular, compounds with a three-carbon linker displayed selective and stronger potency than those with two-carbon and four-carbon linkers. Interestingly, six compounds, 9b, 9c, 9d, 9o, 9q and 9u displayed more effective activity than the standard drug, bupropion. The provided SAR data and potent biological activity can offer useful guidelines for designing dual norepinephrine and dopamine reuptake inhibitors as effective therapeutic agents for treatment of several central nervous system diseases.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2016.09.005