title: Exploration of substituted arylpiperazine-tetrazoles as promising dual norepinephrine and dopamine reuptake inhibitors.
abstract: 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.
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 61186, Republic of Korea.
authors.forename: Suresh
authors.initials: S
authors.lastname: Paudel
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 61186, Republic of Korea.
authors.forename: Srijan
authors.initials: S
authors.lastname: Acharya
authors.affiliation: College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 58554, Republic of Korea.
authors.forename: Goo
authors.initials: G
authors.lastname: Yoon
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 61186, Republic of Korea. Electronic address: kmkim@jnu.ac.kr.
authors.forename: Kyeong-Man
authors.initials: KM
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 61186, Republic of Korea. Electronic address: shcheon@jnu.ac.kr.
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Cheon
mesh_terms: D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D015394:Molecular Structure; D009638:Norepinephrine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D010879:Piperazines; D013777:Tetrazoles; D004298:Dopamine; D009638:Norepinephrine
keywords: Arylpiperazine–tetrazoles; Dopamine reuptake inhibitors; Norepinephrine reuptake inhibitors; Selective norepinephrine and dopamine reuptake inhibitors