Therapeutic Use of Fluorinated Nucleosides – Progress in Patents

Abstract

Fluorinated nucleosides constitute a large class of chemotherapeutics approved for clinical use. The pharmacokinetic and pharmacodynamic properties of a drug can be affected, as a consequence of modulation of electronic, lipophilic and steric parameters, by the introduction of fluorine into the structure of drug-like molecule. Herein, we focus on fluorinated-nucleoside analogs, their therapeutic use and applications based on the patent literature from 2014 to 2018. We briefly discuss the clinical properties of anticancer and antiviral fluorine-containing nucleos(t)ides FDA-approved or in development, and highlight their resistance mechanisms and limitations in the clinic. We emphasize patent inventions related to improved synthetic methods towards selected nucleos(t)ide analogs including the phosphoramidate sofosbuvir and 18 F-labelled nucleosides FLT and FMAU, used as a 18 F-PET tracers.

Fluorinated Nucleosides: Synthesis, Modulation in Conformation and Therapeutic Application

“…In the last twelve years, radical fluorination has become the choice of method for organic chemists [16] but still, we are waiting for a general method of fluorination. There are few reviews available that are specifically dedicated to fluoro‐nucleoside analogs synthesis and their biological study [2,3c,10,13b,d,e,f] . But none is available which also summarizes the influence of fluoro substituent on the conformation of the nucleoside.…”

The Synthesis and Glycoside Formation of Polyfluorinated Carbohydrates

“…While the synthesis of polyfluorinated nucleosides is included, nucleoside formation of polyfluorinated sugar donors is not exhaustively covered. Reviews discussing fluorinated nucleosides are available. − …”

The evolution of nucleosidic analogues: self-assembly of prodrugs into nanoparticles for cancer drug delivery

“…The improvements that traditional analogs have undergone, coupled with the ability of using them in the treatment of a wide range of cancers, have solidied the role of nucleoside analogs as a signicant chemotherapeutic agent, not to mention a growth in their popularity that occurred with the understanding of their exact mechanism of action. [5][6][7][8][9] However, traditional chemotherapeutics display a high toxicity prole with a small therapeutic window, leading to different severe side effects and a lowered efficacy due to the cancer cell's ability of drug efflux through active pumps called "multidrug resistance". 10,11 Consequently, several novel approaches are stemming to address and overcome these shortcomings, namely the prodrug strategy and nanoparticle drug delivery systems (nano-DDSs).…”