Potent haloperidol derivatives covalently binding to the dopamine D2 receptor

Schwalbe T, Kaindl J, Hübner H, Gmeiner P (2017)

Publication Status: Published

Publication Type: Journal article, Original article

Publication year: 2017

Journal

Publisher: PERGAMON-ELSEVIER SCIENCE LTD

Book Volume: 25

Pages Range: 5084-5094

Journal Issue: 19

DOI: 10.1016/j.bmc.2017.06.034

Abstract

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.

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APA:

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://doi.org/10.1016/j.bmc.2017.06.034

MLA:

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

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