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

Article abstract of 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 π-π-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.