Synthesis and in vitro evaluation of fluorinated diphenyloxide derivatives and sulfur analogs as serotonin transporter ligands

Bioorg Med Chem. 2010 Jan 1;18(1):236-41. doi: 10.1016/j.bmc.2009.10.062. Epub 2009 Nov 4.

Abstract

As the serotonin transporter (SERT) is involved in several neurodegenerative and psychiatric disorders; radiopharmaceuticals to image the SERT by PET would be valuable in studying these diseases. To this end we synthesized diphenyloxide derivatives and sulfide analogs, as new tracers, incorporating a fluorine or oxyalkyl fluorinated group on 4' or 5'-position on phenyl ring B. Three of these exhibited good to high in vitro affinity (7<K(i)<8 nM) and selectivity for the SERT over the other monoamine transporters.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding, Competitive
  • Cell Line, Tumor
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Halogenation
  • Humans
  • Ligands
  • Norepinephrine Plasma Membrane Transport Proteins / metabolism
  • Phenyl Ethers / chemical synthesis
  • Phenyl Ethers / chemistry*
  • Phenyl Ethers / pharmacology*
  • Serotonin Plasma Membrane Transport Proteins / metabolism*
  • Sulfides / chemical synthesis
  • Sulfides / chemistry
  • Sulfides / pharmacology

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • Ligands
  • Norepinephrine Plasma Membrane Transport Proteins
  • Phenyl Ethers
  • SLC6A2 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Sulfides