Fluorinated Nucleosides as an Important Class of Anticancer and Antiviral Agents

Abstract

Fluorine-containing nucleoside analogues represent a significant class of FDA approved chemotherapeutics widely used in the clinic. The incorporation of fluorine into drug-like agents modulates lipophilic, electronic and steric parameters thus influencing pharmacodynamic and pharmacokinetic properties of drugs. Fluorine can block oxidative metabolism of drugs and the formation of undesired metabolites by changing H-bonding interactions. In this review, we focus our attention on chemical fluorination reagents and methods used in the nucleoside analogues field, including PET radiochemistry. We briefly discuss both the cellular biology and clinical properties of FDA-approved and fluorine-containing nucleoside/nucleotide analogues in development as well as common resistance mechanisms associated with their use. Finally, we emphasize pro-nucleotide strategies used to improve therapeutic outcome of nucleoside analogues in the clinic.

Adopting STING agonist cyclic dinucleotides as a potential adjuvant for SARS-CoV-2 vaccine

“…The better performance of CDG SF could be owed to the fluorine modification which brought CDG SF with improved liposolubility and stability. 18 These results indicated that CDG SF was capable of stimulating STING pathway efficiently and might be a better clinical choice relative to dithio CDG. Besides, the poor results of dithio CDG and CDG SF without transfection further highlighted the importance and urgency of developing the delivery method ( Fig.…”

Agonists and inhibitors of the STING pathway: Potential agents for immunotherapy

“…The prodrug CDG‐C14 possesses better IFN‐β induction capability over the unmodified CDG. Fluorine is often used as a substitute for H or OH in drug design since it can enhance the stability (due to polarized C–F bond) and lipophilicity with minimal steric perturbation . The Sintim group synthesized 2′‐F‐CDG (Figure B) with Jones’ route (Figure ) via the adoption of N ‐isobutyryl‐2′‐F guanosine phosphoramidite as the starting material .…”

Synthesis of fluorinated acyclic nucleoside phosphonates with 5-azacytosine base moiety

“…Fluorinated derivatives, especially nucleoside and nucleotide analogues are compounds of great interest [14]. gemcitabine) or antivirals (trifluridine, sofosbuvir) [16,17]. In clinical practice, fluorinated nucleosides are utilised as effective cytostatics (e.g.…”