Development of a bivalent dopamine D2 receptor agonist

Kühhorn J, Götz A, Hübner H, Thompson D, Whistler J, Gmeiner P (2011)

Publication Language: English

Publication Type: Journal article, Original article

Publication year: 2011

Journal

Journal of Medicinal Chemistry American Chemical Society

Original Authors: Kuhhorn J., Gotz A., Hubner H., Thompson D., Whistler J., Gmeiner P.

Publisher: American Chemical Society

Book Volume: 54

Pages Range: 7911-7919

Journal Issue: 22

DOI: 10.1021/jm2009919

Abstract

Bivalent D agonists may function as useful molecular probes for the discovery of novel neurological therapeutics. On the basis of our recently developed bivalent dopamine D receptor antagonists of type 1, the bivalent agonist 2 was synthesized when a spacer built from 22 atoms was employed. Compared to the monovalent control compound 6 containing a capped spacer, the bis-aminoindane derivative 2 revealed substantial steepening of the competition curve, indicating a bivalent binding mode. Dimer-specific Hill slopes were not a result of varying functional properties because both the dopaminergic 2 and the monovalent control agent 6 proved to be D agonists substantially inhibiting cAMP accumulation and inducing D receptor internalization. Investigation of the heterobivalent ligands 8 and 9, containing an agonist and a phenylpiperazine-based antagonist pharmacophore, revealed moderate steepening of the displacement curves and antagonist to very weak partial agonist properties. © 2011 American Chemical Society.

Authors with CRIS profile

Angela Götz Graduiertenzentrum der FAU Harald Hübner Lehrstuhl für Pharmazeutische Chemie Peter Gmeiner Lehrstuhl für Pharmazeutische Chemie

Additional Organisation(s)

Emil-Fischer-Zentrum (Emil Fischer Center)

Involved external institutions

University of California San Francisco (UCSF) US United States (USA) (US)

How to cite

APA:

Kühhorn, J., Götz, A., Hübner, H., Thompson, D., Whistler, J., & Gmeiner, P. (2011). Development of a bivalent dopamine D2 receptor agonist. Journal of Medicinal Chemistry, 54(22), 7911-7919. https://doi.org/10.1021/jm2009919

MLA:

Kühhorn, Julia, et al. "Development of a bivalent dopamine D2 receptor agonist." Journal of Medicinal Chemistry 54.22 (2011): 7911-7919.

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