3-Aryl-3-arylmethoxyazetidines. A new class of high affinity ligands for monoamine transporters

Bioorg Med Chem Lett. 2013 Aug 1;23(15):4404-7. doi: 10.1016/j.bmcl.2013.05.071. Epub 2013 May 29.

Abstract

A series of 3-aryl-3-arylmethoxy-azetidines were synthesized and evaluated for binding affinities at dopamine and serotonin transporters. The 3-aryl-3-arylmethoxyazetidines were generally SERT selective with the dichloro substituted congener 7c (Ki=1.0 nM) and the tetrachloro substituted derivative 7i (Ki=1.3 nM) possessing low nanomolar affinity for the SERT. The 3-(3,4-dichlorophenyl-3-phenylmethoxyazetidine (7g) exhibited moderate affinity at both DAT and SERT transporters and suggests that substitution of the aryl rings can be used to tune the mononamine transporter affinity.

Publication types

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

MeSH terms

  • Azetidines / chemical synthesis
  • Azetidines / chemistry*
  • Azetidines / metabolism
  • Crystallography, X-Ray
  • Dopamine Plasma Membrane Transport Proteins / chemistry*
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Kinetics
  • Ligands
  • Molecular Conformation
  • Protein Binding
  • Serotonin Plasma Membrane Transport Proteins / chemistry*
  • Serotonin Plasma Membrane Transport Proteins / metabolism
  • Structure-Activity Relationship

Substances

  • Azetidines
  • Dopamine Plasma Membrane Transport Proteins
  • Ligands
  • Serotonin Plasma Membrane Transport Proteins