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

Date

2014

Authors

Krogsgaard-Larsen, N.
Jensen, A.
Schrøder, T.
Christoffersen, C.
Kehler, J.

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Journal article

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Journal of Medicinal Chemistry, 2014; 57(13):5823-5828

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Niels Krogsgaard-Larsen, Anders A. Jensen, Tenna J. Schrøder, Claus. T. Christoffersen and Jan Kehler

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Abstract

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 D₂ and serotonin 5-HT₆ receptor subtype, respectively. While the 5-HT₆ ligands were antagonists, the D₂ 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.

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Niels Krogsgaard-Larsen, Anders A. Jensen, Tenna J. Schroder, Claus. T. Christoffersen and Jan Kehler

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