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

  • Bioorg Med Chem. 2016 Nov 1;24(21):5546-5555. doi: 10.1016/j.bmc.2016.09.005.
Suresh Paudel  1 ,  Srijan Acharya  1 ,  Goo Yoon  2 ,  Kyeong-Man Kim  3 ,  Seung Hoon Cheon  4
Affiliations
  • 1. College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 61186, Republic of Korea.
  • 2. College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 58554, Republic of Korea.
  • 3. College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 61186, Republic of Korea. Electronic address: [email protected].
  • 4. College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 61186, Republic of Korea. Electronic address: [email protected].
PMID: 27647372 DOI: 10.1016/j.bmc.2016.09.005
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.

Keywords
Arylpiperazine–tetrazoles; Dopamine reuptake inhibitors; Norepinephrine reuptake inhibitors; Selective norepinephrine and dopamine reuptake inhibitors.