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.
Suresh Paudel  1 ,  Yongkai Cao  1 ,  Shuohan Guo  1 ,  Byeongkwan An  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. 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: [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: 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.