Novel aza-analogous ergoline derived scaffolds as potent serotonin 5-HT₆ and dopamine D₂ receptor ligands.

By introducing distal substituents on a tetracyclic scaffold resembling the ergoline structure, two series of analogues were achieved exhibiting subnanomolar receptor binding affinities for the dopamine D-2 and serotonin S-HT6 receptor subtype, respectively. While the S-HT6 ligands were antagonists, the D-2 ligands displayed intrinsic activities ranging from full agonism to partial agonism with low intrinsic activity. These structures could potentially be interesting for treatment of neurological diseases such as schizophrenia, Parkinson's disease, and cognitive deficits.