Toward Novel Trifluoromethylated Peptidomimetics: A Case Study of Cathepsin C Inhibitors

Herein, both synthetic and theoretical results related to the development of amino acid analogues containing a CF 3 ‐olefinic moiety and their evaluation as potential inhibitors of Cathepsin C are presented. The key synthetic steps include the trifluoromethylation using the Ruppert–Prakash reagent and a Horner–Wadsworth–Emmons olefination to obtain the desired CF 3 ‐alkenyl amino acid derivatives. In recent years, theoretical approaches based on molecular docking have gained significant attention for predicting the biological activity of synthetic compounds as enzyme inhibitors. The research specifically targets Cathepsin C, also known as dipeptidyl peptidase I, a protease that plays a crucial role in activating various degradative enzymes involved in tissue damage during inflammatory diseases.