Synthesis and dopamine transporter affinity of chiral 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(2-hydroxypropyl)piperazines as potential cocaine abuse therapeutic agents

Bioorg Med Chem Lett. 2003 Feb 10;13(3):553-6. doi: 10.1016/s0960-894x(02)00940-x.

Abstract

A series of optically pure phenyl-and non-phenyl-substituted 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(2-hydroxypropyl)piperazines was synthesized and their binding affinity for dopamine transporter (DAT) was investigated. The analogues with a hydroxyl group in the S configuration were more selective for the DAT over the serotonin transporter (SERT) than the corresponding R enantiomers. Compound (+)-11 showed high affinity and selectivity for DAT over the SERT and, therefore, is a potential candidate for the development of a long-acting cocaine abuse therapeutic agent.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cocaine / pharmacology
  • Cocaine-Related Disorders / drug therapy*
  • Conditioning, Operant / drug effects
  • Dopamine Plasma Membrane Transport Proteins
  • Dopamine Uptake Inhibitors / pharmacology
  • Ligands
  • Macaca mulatta
  • Membrane Glycoproteins*
  • Membrane Transport Proteins / drug effects
  • Membrane Transport Proteins / metabolism*
  • Nerve Tissue Proteins*
  • Piperazines / chemical synthesis*
  • Piperazines / pharmacology*
  • Protein Binding
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • Dopamine Uptake Inhibitors
  • Ligands
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Piperazines
  • vanoxerine
  • Cocaine