Design, synthesis and docking study of 4-arylpiperazine carboxamides as monoamine neurotransmitters reuptake inhibitors

Suresh Paudel; Ningning Sun; Daulat Bikram Khadka; Goon Yoon; Kyeong-Man Kim; Seung Hoon Cheon

doi:10.1016/j.bmc.2018.06.043

Design, synthesis and docking study of 4-arylpiperazine carboxamides as monoamine neurotransmitters reuptake inhibitors

Bioorg Med Chem. 2018 Aug 7;26(14):4127-4135. doi: 10.1016/j.bmc.2018.06.043. Epub 2018 Jul 2.

Authors

Suresh Paudel¹, Ningning Sun¹, Daulat Bikram Khadka¹, Goon Yoon², Kyeong-Man Kim³, Seung Hoon Cheon⁴

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: kmkim@jnu.ac.kr.
⁴ College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 61186, Republic of Korea. Electronic address: shcheon@jnu.ac.kr.

PMID: 30007567
DOI: 10.1016/j.bmc.2018.06.043

Abstract

Rational drug design method has been used to generate 4-arylpiperazine carboxamides in an effort to develop safer, more potent and effective monoamine neurotransmitters reuptake inhibitors. Out of twenty-seven synthesized compounds, compound 9 displayed potent monoamine neurotransmitter reuptake inhibitory activity against HEK cells transfected with hSERT or hNET. A Surflex-Dock docking model of 9 was also studied.

Keywords: 4-Arylpiperazine carboxamide; Docking; Norepinephrine reuptake inhibitor; Serotonin reuptake inhibitor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Dose-Response Relationship, Drug
Drug Design*
HEK293 Cells
Humans
Molecular Docking Simulation
Molecular Structure
Neurotransmitter Uptake Inhibitors / chemical synthesis
Neurotransmitter Uptake Inhibitors / chemistry
Neurotransmitter Uptake Inhibitors / pharmacology*
Norepinephrine Plasma Membrane Transport Proteins / antagonists & inhibitors*
Norepinephrine Plasma Membrane Transport Proteins / metabolism
Piperazine / chemical synthesis
Piperazine / chemistry
Piperazine / pharmacology*
Serotonin Plasma Membrane Transport Proteins / metabolism*
Structure-Activity Relationship

Substances

Neurotransmitter Uptake Inhibitors
Norepinephrine Plasma Membrane Transport Proteins
Serotonin Plasma Membrane Transport Proteins
Piperazine