Synthesis and dopaminergic activity of some 3-(1,2,3,6-tetrahydro-1-pyridylalkyl)indoles. A novel conformational model to explain structure-activity relationships

J Med Chem. 1992 Oct 30;35(22):4020-6. doi: 10.1021/jm00100a006.


The synthesis and dopaminergic properties of a novel type of dopamine agonist is described. The number and kind of essential structural elements differ significantly from that of the rigid apomorphine-type dopamine agonists. Using standard molecular modeling techniques, a conformational model is developed proposing a U-shaped conformation which might be energetically preferred through aromatic pi-pi-interactions between both of the electron rich aromatic structural elements of this class of compounds. Superimposition of conformations of the lead compound 28 with apomorphine yields a novel model explaining the atypical structure-activity relationships found in this class of indolealkylamines.

MeSH terms

  • Animals
  • Binding, Competitive
  • Corpus Striatum / metabolism
  • Dopamine Agents / chemical synthesis*
  • Dopamine Agents / metabolism
  • Dopamine Agents / pharmacology
  • In Vitro Techniques
  • Indoles / chemical synthesis*
  • Indoles / metabolism
  • Indoles / pharmacology
  • Male
  • Models, Molecular
  • Molecular Conformation
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine D2 / metabolism
  • Stereotyped Behavior / drug effects
  • Structure-Activity Relationship


  • Dopamine Agents
  • Indoles
  • Receptors, Dopamine D2
  • 3-(4-(4-phenyl-1,2,3,6-tetrahydropyridyl-1)-butyl)indole