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.

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