Synthesis and dopaminergic activity of some 3-(1,2,3,6-tetrahydro-1-pyridylalkyl)indoles. A novel conformational model to explain structure-activity relationships.
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.
E. Merck Darmstadt, Preclinical Pharmaceutical Research and Central Analytical Laboratory, Germany.
H
H
Böttcher
G
G
Barnickel
H H
HH
Hausberg
A F
AF
Haase
C A
CA
Seyfried
V
V
Eiermann
D000818:Animals; D001667:Binding, Competitive; D003342:Corpus Striatum / Q000378:metabolism; D015259:Dopamine Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008958:Models, Molecular; D008968:Molecular Conformation; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects; D013329:Structure-Activity Relationship
D015259:Dopamine Agents; D007211:Indoles; D017448:Receptors, Dopamine D2; C037307:3-(4-(4-phenyl-1,2,3,6-tetrahydropyridyl-1)-butyl)indole