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

In this study, we describe the synthesis of novel dipeptide analogs of (E)-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.