CHIRAL, FLUORINE-CONTAINING PHARMACEUTICALS

• Date: 2025
• Main Authors: Han, Jianlin, Wzorek, Alicja, Dhawan, Gagan, Zhang, Wei, Sorochinsky, Alexander, Baecker, Daniel, Ono, Taizo, Klika, Karel, Soloshonok, Vadim
• Format: Article
• Language: English
• Published: V.I.Vernadsky Institute of General and Inorganic Chemistry 2025
• Online Access: https://ucj.org.ua/index.php/journal/article/view/710
• Journal Title: Ukrainian Chemistry Journal

Fluorine is a key element in drug design due to its ability to enhance metabolic stability, binding affinity, and bioavailability. Fluorine’s properties lead to more stable drugs with longer half-lives, reducing dosing frequency and improving patient compliance. Its small size and high electronegativity also improve binding affinity, resulting in more effective treatments with lower doses. For example, fluorine increases a compound’s ability to cross cell memb­ranes. This article highlights advancements in chiral, fluorine-containing pharmaceuticals introduced over the past five years, focusing on their synthesis, therapeutic benefits, mechanisms of action, and the impact of fluorine on efficacy and safety. Chiral molecules, essential in drug development, exist in two enantiomeric forms with distinct biological activities. Synthesizing chiral, fluorine-containing drugs involves techniques like asymmetric synthesis to produce pure enantiomers, resulting in drugs with increased potency, selectivity, and reduced side effects. Understanding their mechanisms of action provides valuable insights into efficacy and safety. Reviewing recently FDA-approved chiral drugs offers insights into fluorine chemistry in drug development and future therapeutic innovations. Recent FDA approvals highlight the significance of chiral, fluorine-containing drugs in various therapeutic areas, enabling targeted and effective treatments. Analyzing these approvals reveals trends shaping drug development’s future. The article also addresses the need for more research into self-disproportionation of enantiomers (SDE) in chiral, fluorinated compounds and concerns about excessive fluorine levels. SDE can affect pharmaceutical product purity. Research into SDE in fluorinated compounds ensures drug quality. Additionally, fluorine’s widespread use raises environmental and health concerns, necessitating studies on long-term effects and mitigation strategies.