Synthesis and biological evaluation of 3-phenethylazetidine derivatives as triple reuptake inhibitors

Jun Yun; Minsoo Han; Chiman Song; Seung Hoon Cheon; Kihang Choi; Hoh-Gyu Hahn

doi:10.1016/j.bmcl.2014.06.026

Synthesis and biological evaluation of 3-phenethylazetidine derivatives as triple reuptake inhibitors

Bioorg Med Chem Lett. 2014 Aug 1;24(15):3234-7. doi: 10.1016/j.bmcl.2014.06.026. Epub 2014 Jun 18.

Authors

Jun Yun¹, Minsoo Han², Chiman Song², Seung Hoon Cheon³, Kihang Choi⁴, Hoh-Gyu Hahn⁵

Affiliations

¹ Chemical Kinomics Research Center, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea; Department of Chemistry, Research Institute for Natural Sciences, Korea University, Seoul 136-701, Republic of Korea.
² Chemical Kinomics Research Center, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea.
³ College of Pharmacy, Chonnam National University, Gwangju 500-757, Republic of Korea.
⁴ Department of Chemistry, Research Institute for Natural Sciences, Korea University, Seoul 136-701, Republic of Korea.
⁵ Chemical Kinomics Research Center, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea. Electronic address: hghahn@kist.re.kr.

PMID: 24974340
DOI: 10.1016/j.bmcl.2014.06.026

Abstract

We report the synthesis of 3-phenethylazetidine derivatives 2 and their biological activities against 5-HT, NE and DA transporters as well as microsomal stability, CYP inhibition, and hERG inhibition profiles. Compound 2at showed most potent triple reuptake inhibitor with good selectivity as a candidate for depression.

Keywords: 3-Phenethylazetidines; Antidepressant; Depression; Triple reuptake inhibitor.

Publication types

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

MeSH terms

Azetidines / chemical synthesis
Azetidines / chemistry
Azetidines / pharmacology*
Biological Transport / drug effects
Cytochrome P-450 Enzyme Inhibitors / chemical synthesis
Cytochrome P-450 Enzyme Inhibitors / chemistry
Cytochrome P-450 Enzyme Inhibitors / pharmacology*
Cytochrome P-450 Enzyme System / metabolism*
Ether-A-Go-Go Potassium Channels / antagonists & inhibitors*
Ether-A-Go-Go Potassium Channels / metabolism
Humans
Molecular Structure
Neurotransmitter Uptake Inhibitors / chemical synthesis
Neurotransmitter Uptake Inhibitors / chemistry
Neurotransmitter Uptake Inhibitors / pharmacology*
Phenyl Ethers / chemical synthesis
Phenyl Ethers / chemistry
Phenyl Ethers / pharmacology*
Plasma Membrane Neurotransmitter Transport Proteins / antagonists & inhibitors*
Plasma Membrane Neurotransmitter Transport Proteins / metabolism
Serotonin / metabolism*
Structure-Activity Relationship

Substances

3-(2-(4-chloro-3-fluorophenyl)-2-(3-fluorophenoxy)ethyl)azetidine
Azetidines
Cytochrome P-450 Enzyme Inhibitors
Ether-A-Go-Go Potassium Channels
Neurotransmitter Uptake Inhibitors
Phenyl Ethers
Plasma Membrane Neurotransmitter Transport Proteins
Serotonin
Cytochrome P-450 Enzyme System