Tricyclic azaergoline analogues: synthesis, structural modifications, and pharmacological studies.
As an extension of previous investigations on synthesis and dopamine autoreceptor activity of bicyclic ergoline analogues the tricyclic azaergoline analogues 9a and 9b were synthesized. Furthermore, the geometry of the aromatic beta-ethylamine moiety of 9a,b was modified by stereoselective construction of the cycloheptenyl fused pyrazolopyridine derivative 7 and the aminomethyl substituted tricycle 10. Binding affinity of these compounds at dopamine (DA) receptor sites was investigated employing rat striatum homogenate: The compounds reveal modest to weak, but selective binding to a dopamine D-2 receptor when it is labelled with the DA-autoreceptor agonist [3H]-SND 919. In vivo studies with mice showed that 7, 9a,b, and 10 affect their CNS activity.
Institut für Pharmazie und Lebensmittelchemie, Universität München, Germany.
P
P
Gmeiner
J
J
Sommer
G
G
Höfner
J
J
Mierau
D000818:Animals; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D015259:Dopamine Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004873:Ergolines / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects
D001372:Aza Compounds; D015259:Dopamine Agents; D004873:Ergolines; D011954:Receptors, Dopamine