Fluorinated Nucleosides: Synthesis, Modulation in Conformation and Therapeutic Application

Area of Science:

• Medicinal Chemistry
• Organic Chemistry
• Pharmacology

Background:

• Fluorination of nucleosides has emerged as a key strategy in developing biologically active compounds over the past two decades.
• The unique properties of fluorine atoms enhance metabolic stability, lipophilicity, and intermolecular binding of nucleoside analogs.
• These modifications are crucial for improving pharmacokinetic and pharmacodynamic profiles, enabling compounds to withstand clinical trials.

Purpose of the Study:

• To review the latest advancements in the chemistry of nucleoside fluorination.
• To summarize the biological properties of newly developed fluorinated nucleoside analogs.
• To highlight the influence of fluorine on molecular conformation, oligonucleotide stability, and therapeutic applications.

Main Methods:

• Comprehensive literature review of recent developments in fluorination chemistry applied to nucleosides.
• Analysis of studies focusing on the synthesis of novel fluorinated nucleoside analogs (carbocyclic, acyclic, conformationally biased).
• Evaluation of data on the biological activities and therapeutic potential of these compounds.

Main Results:

• Significant progress has been made in synthesizing diverse fluorinated nucleoside analogs.
• Fluorination demonstrably improves metabolic stability and modulates pharmacokinetic properties.
• Several fluorinated nucleosides are approved by the FDA or in advanced clinical trials for various therapeutic uses.

Conclusions:

• Nucleoside fluorination is a powerful and versatile strategy for drug discovery.
• The judicious incorporation of fluorine leads to compounds with enhanced therapeutic potential.
• Continued research in this area promises further development of novel treatments.