Design and synthesis of 4-benzylpiperidine carboxamides as dual serotonin and norepinephrine reuptake inhibitors

Suresh Paudel; Yongkai Cao; Shuohan Guo; Byeongkwan An; Kyeong-Man Kim; Seung Hoon Cheon

doi:10.1016/j.bmc.2015.08.022

Design and synthesis of 4-benzylpiperidine carboxamides as dual serotonin and norepinephrine reuptake inhibitors

Bioorg Med Chem. 2015 Oct 1;23(19):6418-26. doi: 10.1016/j.bmc.2015.08.022. Epub 2015 Aug 20.

Authors

Suresh Paudel¹, Yongkai Cao¹, Shuohan Guo¹, Byeongkwan An², 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 Jeonnam Development Institute for Korean Traditional Medicine, 288, Udeuraendeu-gil, Anyang-myeon, Jangheung-gun, Jeollanam-do 59338, 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: 26337019
DOI: 10.1016/j.bmc.2015.08.022

Abstract

A series of 4-benzylpiperidine carboxamides were designed and synthesized, and tested for their dual (serotonin and norepinephrine) reuptake inhibition. The synthesis of 4-benzylpiperidine carboxamides involved two main steps: amidation and substitution. Derivatives with 3 carbon linker displayed better activity than with 2 carbon linker. 4-Biphenyl- and 2-naphthyl-substituted derivatives 7e and 7j showed greater dual reuptake inhibition than standard drug venlafaxine HCl.

Keywords: 4-Benzylpiperidine carboxamide; Norepinephrine reuptake inhibitor; Serotonin reuptake inhibitor.

Publication types

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

MeSH terms

Amides / chemical synthesis
Amides / chemistry*
Amides / metabolism
Drug Design*
HEK293 Cells
Humans
Norepinephrine Plasma Membrane Transport Proteins / chemistry
Norepinephrine Plasma Membrane Transport Proteins / metabolism
Piperidines / chemistry
Protein Binding
Selective Serotonin Reuptake Inhibitors / chemical synthesis*
Selective Serotonin Reuptake Inhibitors / chemistry
Selective Serotonin Reuptake Inhibitors / metabolism
Serotonin Plasma Membrane Transport Proteins / chemistry
Serotonin Plasma Membrane Transport Proteins / metabolism
Serotonin and Noradrenaline Reuptake Inhibitors / chemical synthesis*
Serotonin and Noradrenaline Reuptake Inhibitors / chemistry
Serotonin and Noradrenaline Reuptake Inhibitors / metabolism
Structure-Activity Relationship

Substances

Amides
Norepinephrine Plasma Membrane Transport Proteins
Piperidines
Serotonin Plasma Membrane Transport Proteins
Serotonin Uptake Inhibitors
Serotonin and Noradrenaline Reuptake Inhibitors
piperidine