Synthesis and monoamine transporter binding properties of 3alpha-(substituted phenyl)nortropane-2beta-carboxylic acid methyl esters. Norepinephrine transporter selective compounds

J Med Chem. 2005 Jun 2;48(11):3852-7. doi: 10.1021/jm058164j.

Abstract

3alpha-(substituted phenyl)nortropane-2beta-carboxylic acid methyl esters (8a-h) showed high affinity for the norepinephrine transporter (NET). The most potent and selective compound was 3alpha-(3-fluoro-4-methylphenyl)nortropane-2beta-carboxylic acid methyl ester (8d), with a Ki of 0.43 nM at the NET and 21- and 55-fold selectivity relative to binding at the dopamine and serotonin transporters. The development of 8d makes available compounds selective for all three transporters from the same structural class.

Publication types

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

MeSH terms

  • Animals
  • Binding, Competitive
  • Brain / metabolism
  • Cocaine / analogs & derivatives*
  • Cocaine / chemical synthesis*
  • Cocaine / chemistry
  • Cocaine / pharmacology
  • Dopamine / metabolism
  • Dopamine Plasma Membrane Transport Proteins
  • In Vitro Techniques
  • Male
  • Membrane Glycoproteins / metabolism
  • Membrane Transport Proteins / metabolism
  • Nerve Tissue Proteins / metabolism
  • Norepinephrine / metabolism*
  • Norepinephrine Plasma Membrane Transport Proteins
  • Radioligand Assay
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / metabolism
  • Serotonin Plasma Membrane Transport Proteins
  • Structure-Activity Relationship
  • Symporters / metabolism*

Substances

  • 3-(3-fluoro-4-methylphenyl)nortropane-2-carboxylic acid methyl ester
  • Dopamine Plasma Membrane Transport Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Norepinephrine Plasma Membrane Transport Proteins
  • Serotonin Plasma Membrane Transport Proteins
  • Slc6a2 protein, rat
  • Slc6a4 protein, rat
  • Symporters
  • Serotonin
  • Cocaine
  • Dopamine
  • Norepinephrine