DprE1 Inhibitors in Clinical Trials: A Route Scouting Approach

Abstract Tuberculosis (TB), caused by Mycobacterium tuberculosis , remains a significant global health burden, with over 8.2 million new cases reported in 2023. Among promising targets for drug development, the decaprenylphosphoryl‐β‐D‐ribose 2′‐epimerase (DprE1), a key enzyme in mycobacterial cell wall biosynthesis. Its extracellular presence and specificity to mycobacteria make DprE1 an attractive target for selective anti‐TB therapies. This review explores the recent detailed advancements in synthetic scheme of DprE1 inhibitors which are under clinical trial, particularly BTZ‐043, PBTZ‐169 (macozinone), OPC‐167832, and TBA‐7371. A comparative analysis of synthetic routes, cost effective strategy and feasibility for large‐scale production are also discussed for the mentioned inhibitors.