Vol. 7, Issue 2, Part B (2025)

Fluorine has become an indispensable element in modern drug discovery, with its unique electronic and steric properties offering medicinal chemists a powerful tool to fine-tune biological activity. The introduction of fluorine atoms into small molecules can modulate acidity and lipophilicity, alter conformational preferences, and enhance membrane permeability. These subtle effects frequently translate into improved pharmacokinetics, greater target selectivity, and resistance to metabolic degradation. Over the past two decades, fluorine substitution has been increasingly represented in approved drugs across diverse therapeutic areas, including oncology, antiviral therapy, neurology, and cardiovascular disease. Parallel advances in synthetic chemistry, particularly late-stage fluorination and the development of new fluorine-containing motifs, have greatly expanded the possibilities for drug design. Beyond therapeutic agents, fluorine has also enabled the creation of diagnostic tools, most notably through the use of fluorine-18 in positron emission tomography imaging. This review highlights the strategic role of fluorine in drug discovery, discusses representative case studies, and examines emerging trends that are likely to shape the future of fluorine-enabled medicinal chemistry.