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

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.

• Authors: Ling-Wei Hsin, Thomas Prisinzano, Chavon R Wilkerson, Christina M Dersch, Robert Horel, Arthur E Jacobson, Richard B Rothman, Kenner C Rice
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 13 Issue 3 Pg. 553-6 (Feb 10 2003) ISSN: 0960-894X [Print] England
• PMID: 12565970 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

• 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, metabolism)
• Nerve Tissue Proteins
• Piperazines (chemical synthesis, pharmacology)
• Protein Binding
• Stereoisomerism
• Structure-Activity Relationship