Nucleosides with fluorinated nucleobases for antiviral and anticancer therapies

ABSTRACT Nucleosides have garnered significant attention for their promising antiviral and antitumor properties. Fluorine atoms imbue fluorinated compounds with distinct physical and chemical characteristics. Following the success of 5-fluorouracil (5-FU), many fluorinated nucleosides are currently being clinically investigated or already on the market. This review provides a comprehensive overview of nucleosides approved or clinically tested with fluorinated nucleobases, highlighting their therapeutic potential in antiviral and antitumor treatments. The topics covered include drug discovery strategies, structure-activity relationship (SAR) studies, mechanisms of action, representative chemical or biocatalytic syntheses, as well as challenges and future directions in nucleoside-based new drug development.