Synthesis of dopamine transporter selective 3-[2-(diarylmethoxyethylidene)]-8-alkylaryl-8-azabicyclo[3.2.1]octanes

Bioorg Med Chem Lett. 2003 Feb 24;13(4):629-32. doi: 10.1016/s0960-894x(02)01051-x.

Abstract

A series of 3-[2-(diarylmethoxyethylidene)]-8-alkylaryl-8-azabicyclo[3.2.1]octanes was synthesized and the binding affinities of the compounds were determined at the dopamine and serotonin transporters. The 8-phenylpropyl analogues 8a (K(i)=4.1 nM) and 8b (K(i)=3.7 nM) were the most potent compounds of the series with binding affinities 3 times greater than GBR-12909. In addition, 8a (SERT/DAT=327) was over 300-fold more selective for the dopamine transporter than the serotonin transporter.

Publication types

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

MeSH terms

  • Animals
  • Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis*
  • Bridged Bicyclo Compounds, Heterocyclic / chemistry
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
  • Caudate Nucleus / metabolism
  • Dopamine Plasma Membrane Transport Proteins
  • Membrane Glycoproteins*
  • Membrane Transport Modulators*
  • Membrane Transport Proteins / antagonists & inhibitors*
  • Membrane Transport Proteins / metabolism
  • Nerve Tissue Proteins*
  • Octanes / chemical synthesis
  • Octanes / chemistry
  • Octanes / pharmacology
  • Protein Binding
  • Rats
  • Structure-Activity Relationship

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Dopamine Plasma Membrane Transport Proteins
  • Membrane Glycoproteins
  • Membrane Transport Modulators
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Octanes
  • Slc6a3 protein, rat