Tricyclic azaergoline analogues: Synthesis, structural modifications, and pharmacological studies

Article abstract of DOI:10.1002/ardp.19923251007

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 β-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 19 affect their CNS activity.