Synthesis and dopamine transporter binding affinities of 3alpha-benzyl-8-(diarylmethoxyethyl)-8-azabicyclo[3.2.1]octanes

Bioorg Med Chem Lett. 2002 Sep 2;12(17):2387-90. doi: 10.1016/s0960-894x(02)00464-x.

Abstract

A series of 3alpha-benzyl-8-(diarylmethoxyethyl)-8-azabicyclo[3.2.1]octanes was synthesized and the binding affinities of the compounds were determined at the dopamine transporter. The unsubstituted analogue 7b (K(i)=98nM) was the most potent compound of the series with binding affinity three-times greater than cocaine and only 5-fold less than GBR-12909. The structure-activity data for 7a-f suggests that these compounds may be binding at the dopamine transporter in a similar fashion to GBR 12909.

Publication types

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

MeSH terms

  • Bridged Bicyclo Compounds / chemical synthesis
  • Bridged Bicyclo Compounds / pharmacology
  • Dopamine Plasma Membrane Transport Proteins
  • Dopamine Uptake Inhibitors / chemical synthesis*
  • Dopamine Uptake Inhibitors / pharmacology
  • Humans
  • Membrane Glycoproteins*
  • Membrane Transport Modulators
  • Membrane Transport Proteins / antagonists & inhibitors
  • Membrane Transport Proteins / metabolism*
  • Nerve Tissue Proteins*
  • Octanes / chemical synthesis
  • Octanes / pharmacology
  • Protein Binding
  • Structure-Activity Relationship

Substances

  • Bridged Bicyclo Compounds
  • Dopamine Plasma Membrane Transport Proteins
  • Dopamine Uptake Inhibitors
  • Membrane Glycoproteins
  • Membrane Transport Modulators
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Octanes