Update on FDA-approved fluorinated drugs (2023–2025): Structural chemistry, polypharmacology, and antiparasitic potential

Abstract

Fluorine's high electronegativity and small atomic size enhance drug potency, selectivity, metabolic stability, and pharmacokinetics due to its unique properties. Fluorine substitution in drug research improves biological activity and stability. Half of the most successful drugs (blockbuster drugs) contain fluorine atoms. Fluorocarbons, known for their chemical and biological inertness, high gas-dissolving capacity, low surface tension, and excellent spreading characteristics, are used in oxygen delivery. Fluorine's unique properties make it a key component in designing higher-order structural motifs, enhancing the properties of molecules in vitro and in vivo. Aromatic F and CF 3 and aliphatic substitutions, offering advances in treating diseases like cancer, genetic disorders, eye disease, and neurological disorders. Fluorine-containing drugs have been profiled, targeting various therapeutic areas including HIV, VMS, and PBS. This review focuses on the development of fluorinated drugs approved by the US Food and Drug Administration (FDA) from 2023 to 2025, and 34 fluorinated drugs achieved approval during this period. FDA-approved drugs include those targeting the central nervous system, digestive system, anti-inflammatory, and metabolic systems, as well as early-stage compounds such as anticancer drugs, and antiparasitic drugs. This brief study highlights the discovery of each of these fluorine-containing medications during the last three years, including their approval, composition, sponsors, indication, synthesis, and mechanism of action. The related future trend is also briefly mentioned. However, fluorinated antiparasitic drugs are less in recent approvals, highlighting both the potential and the need for fluorine-based innovation in parasitology.