Design and synthesis of 4-benzylpiperidine carboxamides as dual serotonin and norepinephrine reuptake inhibitors.
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.
College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 61186, Republic of Korea.
Suresh
S
Paudel
College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 61186, Republic of Korea.
Yongkai
Y
Cao
College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 61186, Republic of Korea.
Shuohan
S
Guo
Jeonnam Development Institute for Korean Traditional Medicine, 288, Udeuraendeu-gil, Anyang-myeon, Jangheung-gun, Jeollanam-do 59338, Republic of Korea.
Byeongkwan
B
An
College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 61186, Republic of Korea. Electronic address: kmkim@jnu.ac.kr.
Kyeong-Man
KM
Kim
College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 61186, Republic of Korea. Electronic address: shcheon@jnu.ac.kr.
Seung Hoon
SH
Cheon
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D015195:Drug Design; D057809:HEK293 Cells; D006801:Humans; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism; D010880:Piperidines / Q000737:chemistry; D011485:Protein Binding; D050486:Serotonin Plasma Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
D000577:Amides; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010880:Piperidines; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors; C032727:piperidine
4-Benzylpiperidine carboxamide; Norepinephrine reuptake inhibitor; Serotonin reuptake inhibitor