Bicyclo[3.2.1]octanes: synthesis and inhibition of binding at the dopamine and serotonin transporters

Bioorg Med Chem Lett. 1999 Mar 22;9(6):857-62. doi: 10.1016/s0960-894x(99)00098-0.

Abstract

Herein we report the synthesis of a series of bicyclo[3.2.1]octanes and their binding characteristics at the dopamine and serotonin transporters. The data confirm that a heteroatom at position 8 of the tropane nucleus is not a prerequisite for binding since the bicyclo[3.2.1]octanes prove potent inhibitors of both transporters. Therefore the three-dimensional topology of the ligand may be more important than specific functionality with respect to stereospecific binding at the acceptor site.

Publication types

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

MeSH terms

  • Bridged Bicyclo Compounds / chemical synthesis*
  • Bridged Bicyclo Compounds / pharmacology
  • Carrier Proteins / metabolism*
  • Cocaine / chemistry
  • Dopamine Plasma Membrane Transport Proteins
  • Inhibitory Concentration 50
  • Kinetics
  • Membrane Glycoproteins / metabolism*
  • Membrane Transport Proteins*
  • Models, Chemical
  • Nerve Tissue Proteins*
  • Serotonin Plasma Membrane Transport Proteins

Substances

  • Bridged Bicyclo Compounds
  • Carrier Proteins
  • Dopamine Plasma Membrane Transport Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Serotonin Plasma Membrane Transport Proteins
  • Cocaine