Design, Synthesis, and Biological Activity of ( <i>E</i> )-α-Fluorovinylphosphonate-Based Reversible Cathepsin C Inhibitors

In this study, we describe the synthesis of novel dipeptide analogs of (<i>E</i>)-α-fluorovinylphosphonates, with a key step involving the Horner-Wadsworth-Emmons (HWE) reaction. The synthesized compounds were evaluated as potential reversible inhibitors of the cathepsin C enzyme. Comprehensive characterization of the target molecules was performed, and their inhibitory activity was assessed. Additionally, molecular docking studies were conducted to elucidate the binding interactions of the synthesized derivatives within the cathepsin C active site. The results highlight promising structural features for the design of effective enzyme inhibitors and provide a foundation for further optimization of fluorovinylphosphonate-based dipeptides.

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Publication Details

Journal
The Journal of Organic Chemistry
Published
2026-02-13
DOI
https://doi.org/10.1021/acs.joc.5c02923
Primary Topic
Protease and Inhibitor Mechanisms
Type
article
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article

Design, Synthesis, and Biological Activity of ( E )-α-Fluorovinylphosphonate-Based Reversible Cathepsin C Inhibitors

Damian Nowak, Małgorzata Pawełczak, Marcin Kaźmierczak, Monika Bilska-Markowska et al.
The Journal of Organic Chemistry
Protease and Inhibitor Mechanisms
article

Design, Synthesis, and Biological Activity of ( E )-α-Fluorovinylphosphonate-Based Reversible Cathepsin C Inhibitors

Damian Nowak, Małgorzata Pawełczak, Marcin Kaźmierczak, Monika Bilska-Markowska, Marcin Hoffmann, Katarzyna Wiśniewska
article en

Abstract

In this study, we describe the synthesis of novel dipeptide analogs of (<i>E</i>)-α-fluorovinylphosphonates, with a key step involving the Horner-Wadsworth-Emmons (HWE) reaction. The synthesized compounds were evaluated as potential reversible inhibitors of the cathepsin C enzyme. Comprehensive characterization of the target molecules was performed, and their inhibitory activity was assessed. Additionally, molecular docking studies were conducted to elucidate the binding interactions of the synthesized derivatives within the cathepsin C active site. The results highlight promising structural features for the design of effective enzyme inhibitors and provide a foundation for further optimization of fluorovinylphosphonate-based dipeptides.

The Journal of Organic ChemistryVol. 91(8)
University of Opole (PL), Adam Mickiewicz University in Poznań (PL)
Clean water and sanitation
Openalex Percentile: Top 58%
Protease and Inhibitor Mechanisms
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Design, Synthesis, and Biological Activity of ( <i>E</i> )-α-Fluorovinylphosphonate-Based Reversible Cathepsin C Inhibitors — Damian Nowak, Małgorzata Pawełczak, et al. · The Journal of Organic Chemistry (2026) | TGRS Research Map | TGRS