Synthesis of macrocyclic α-ketoamide as a selective and reversible immunoproteasome inhibitor

Rui Ding; Daniel J. Wilson; Liqiang Chen

doi:10.1007/s00044-020-02678-2

Synthesis of macrocyclic α-ketoamide as a selective and reversible immunoproteasome inhibitor

Rui Ding, Daniel J. Wilson, Liqiang Chen

Center for Drug Design

Research output: Contribution to journal › Article › peer-review

Abstract

In recent years, the human immunoproteasome has emerged as an attractive therapeutic target for various diseases, leading to a growing interest in the discovery of immunoproteasome inhibitors that selectively target specific subunits. Herein we report the design, synthesis, and evaluation of a new immunoproteasome inhibitor that feature a macrocyclic ring containing an internal α-ketoamide warhead. This compound is a selective and reversible inhibitor of immunoproteasome subunits β1i and β5i and shows essentially no inhibition of constitutive proteasome subunits. [Figure not available: see fulltext.]

Original language	English (US)
Pages (from-to)	410-420
Number of pages	11
Journal	Medicinal Chemistry Research
Volume	30
Issue number	2
DOIs	https://doi.org/10.1007/s00044-020-02678-2
State	Published - Feb 2021

Bibliographical note

Funding Information:
This work was supported by the Center for Drug Design at the University of Minnesota. We thank Prof Rodney Johnson on the use of the ozone generator in his laboratory.

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.

Keywords

Immunoproteasome
Immunoproteasome inhibitors
Ketoamide
Macrocyclic ketoamide
Reversible covalent inhibitors

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Synthesis of macrocyclic α-ketoamide as a selective and reversible immunoproteasome inhibitor

Abstract

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Keywords

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