Potent haloperidol derivatives covalently binding to the dopamine D2 receptor

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Details zur Publikation

Autorinnen und Autoren: Schwalbe T, Kaindl J, Hübner H, Gmeiner P
Zeitschrift: Bioorganic & Medicinal Chemistry
Jahr der Veröffentlichung: 2017
Band: 25
Heftnummer: 19
Seitenbereich: 5084-5094
ISSN: 0968-0896


The dopamine D-2 receptor (D2R) is a common drug target for the treatment of a variety of neurological disorders including schizophrenia. Structure based design of subtype selective D2R antagonists requires high resolution crystal structures of the receptor and pharmacological tools promoting a better understanding of the protein-ligand interactions. Recently, we reported the development of a chemically activated dopamine derivative (FAUC150) designed to covalently bind the L94C mutant of the dopamine D-2 receptor. Using FAUC150 as a template, we elaborated the design and synthesis of irreversible analogs of the potent antipsychotic drug haloperidol forming covalent D2R-ligand complexes. The disulfide- and Michael acceptor-functionalized compounds showed significant receptor affinity and an irreversible binding profile in radioligand depletion experiments. (C) 2017 Elsevier Ltd. All rights reserved.

FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Gmeiner, Peter Prof. Dr.
Lehrstuhl für Pharmazeutische Chemie
Hübner, Harald Dr.
Lehrstuhl für Pharmazeutische Chemie
Kaindl, Jonas
Lehrstuhl für Pharmazeutische Chemie
Schwalbe, Tobias
Lehrstuhl für Pharmazeutische Chemie

Zusätzliche Organisationseinheit(en)
Emil-Fischer-Zentrum (Emil Fischer Center)


Schwalbe, T., Kaindl, J., Hübner, H., & Gmeiner, P. (2017). Potent haloperidol derivatives covalently binding to the dopamine D2 receptor. Bioorganic & Medicinal Chemistry, 25(19), 5084-5094. https://dx.doi.org/10.1016/j.bmc.2017.06.034

Schwalbe, Tobias, et al. "Potent haloperidol derivatives covalently binding to the dopamine D2 receptor." Bioorganic & Medicinal Chemistry 25.19 (2017): 5084-5094.


Zuletzt aktualisiert 2019-18-07 um 07:35