69123-98-4

Usage

Uses

1. Used as an antiviral agent for the treatment of hepatitis B:
Fialuridine (FIAU) is used as an antiviral agent, specifically for the treatment of hepatitis B virus (HBV) infections. It has shown to inhibit viral replication in woodchuck and duck models of HBV infection. The triphosphate analog of FIAU acts as a potent inhibitor of HBV DNA polymerase activity, thus reducing the level of HBV DNA in the serum of patients with chronic hepatitis B.
2. Used in the selection of clones:
Fialuridine (FIAU) has been utilized in the process of selecting clones, particularly in the context of genetic research and development.

Biochem/physiol Actions

Fialuridine (1-(2-deoxy-2-fluoro-β-d-arabinofuranosyl)-5-iodouracil, or FIAU) and its metabolites blocks DNA polymerase at sites of multiple adjacent analog incorporation, reduces the presence of mtDNA (mitochondrial DNA) and results in mitochondrial structural defects in cultured hepatoblasts. It is considered as an efficient drug against hepatitis B virus (HBV) infection.

Clinical Use

Fialuridine, a nucleoside analog designed for the treatment of hepatitis B virus infection, failed in clinical trials due to fatal hepatotoxicity, occuring after 13 weeks of 0.25 mg/kg qd dosing in HBV infected patients. Both in vitro assays as well as preclinical in vivo tests in mice, rats, dogs, and primates could not predict its hepatotoxic potential. Fialuridine toxicity is thought to be mediated by human-specific impaired mitochondrial function after long-term exposure. We used the micropatterned primary hepatocyte coculture model, HepatoPac?, to assess fialuridine-mediated toxicity in vitro. To confirm the human specific toxicity, also rat, dog and monkey HepatoPac? were exposed to fialuridine. Another nucleoside analog, sofosbuvir, which is on the market for the treatment of hepatitis C virus infection and shows no signs of hepatotoxicity in the clinic, was used to study whether this approach would be able to distinguish a nucleoside analog with clinical chronic DILI finding from a nucleoside analog without DILI findings.

in vitro

previous in-vitro data showed that 1-(2-deoxy-2-fluoro-beta-d-arabinofuranosyl)-5-ethyluracil (feau) had activity against herpes simplex virus types 1 and 2 comparable to that of 1-(2-deoxy-2-fluoro-beta-d-arabinofuranosyl)-5-methyluracil (fmau), fialuridine (fiau), and acyclovir (acv). the cellular toxicity of feau was found to be much lower than that of fiau. biochemical experiments indicated that feau had similar affinity toward thymidine kinases encoded by hsv 1 and 2 and a much lower affinity for cellular thymidine kinase than thymidine [1].

in vivo

the in-vivo antiviral efficiency of feau was compared with that of fiau and acv by using the herpes encephalitis mode. moreover, acv and feau could significantly increase the number of survivors at doses of 50 and 100 mg/kg per day, respectively, and fiau showed significant activity at 25 mg/kg per day in the animal model [1].

references

[1] mansuri, m. m.,ghazzouli, i.,chen, m.s., et al. 1-(2-deoxy-2-fluoro-β-d-arabinofuranosyl)-5-ethyluracil. a highly selective antiherpes simplex agent. journal of medicinal chemistry 30(5), 867-871 (1987).[2] mckenzie r et al. hepatic failure and lactic acidosis due to fialuridine (fiau), an investigational nucleoside analogue for chronic hepatitis b. n engl j med. 1995 oct 26;333(17):1099-105.

InChI:InChI=1/C9H10FIN2O5/c10-5-6(15)4(2-14)18-8(5)13-1-3(11)7(16)12-9(13)17/h1,4-6,8,14-15H,2H2,(H,12,16,17)

Upstream product

• 97614-44-3 2-deoxy-2-fluoro-3,5-di-O-benzoyl-α-D-arabinofuranosyl bromide 
• 69123-94-0 1-(2'-deoxy-2'-fluoro-β-D-arabinofuranosyl)uracil 
• 213136-12-0 1-(3',5'-di-O-benzoyl-2'-deoxy-2'-fluoro-β-D-arabinofuranosyl)-5-bromouracil 
• 69124-02-3 1-(O³-acetyl-O⁵-benzoyl-2-fluoro-β-D-2-deoxy-arabinofuranosyl)-1H-pyrimidine-2,4-dione 
• 97614-42-1 2-O-(imidazolylsulfonyl)-1,3,5-tri-O-benzoyl-α-D-ribofuranose 
• 98855-71-1 ((2R,3R,4S)-3-(benzoyloxy)-5-bromo-4-fluorotetrahydrofuran-2-yl)methyl benzoate 
• 97614-43-2 1,3,5-tri-O-benzoyl-2-deoxy-2-fluoro-α-D-arabinofuranose 
• 97614-45-4 5-iodo-1-(2'-deoxy-2'-fluoro-3',5'-di-O-benzoyl-β-D-arabinofuranosyl)uracil 

Downstream Products

• 157428-24-5 1-(3,5-di-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-N³-benzoyl-5-iodouracil 
• 69123-94-0 1-(2'-deoxy-2'-fluoro-β-D-arabinofuranosyl)uracil 
• 157428-25-6 1-(3,5-di-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-N³-benzoyl-5-<2-(trimethylsilyl)ethynyl>uracil 
• 114652-79-8 1-(2-deoxy-2-fluoro-3,5-di-O-trityl-β-D-arabinofuranosyl)-5-(trifluoromethyl)uracil 
• 95740-25-3 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-<2-(trimethylsilyl)ethynyl>uracil 
• 95740-26-4 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-ethynyluracil 
• 105281-09-2 1-(2,5-dideoxy-2-fluoro-β-D-arabinofuranosyl)-5-iodouracil 
• 105281-08-1 1-(2,5-dideoxy-2-fluoro-β-D-arabinofuranosyl)uracil 
• 105281-01-4 Toluene-4-sulfonic acid (2R,3R,4S,5R)-4-fluoro-3-hydroxy-5-(4-hydroxy-5-iodo-2-oxo-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethyl ester 
• 213136-14-2 1-(2'-deoxy-2'-fluoro-β-D-arabinofuranosyl)-5-(trimethylstannyl)uracil 
• 122757-53-3 1-(2,3-dideoxy-2-fluoro-β-D-glycero-pent-2-enofuranosyl)cytosine 
• 124424-25-5 1-(2,3-dideoxy-2-fluoro-β-D-threo-pentofuranosyl)uracil 
• 119555-47-4 1-(2,3-Dideoxy-2-fluoro-β-D-arabinofuranosyl)-cytosine 
• 124424-33-5 1-<3-O-(methylsulfonyl)-5-O-(monomethoxytrityl)-2-deoxy-2-fluoro-β-D-arabinofuranosyl)uracil 

Relevant academic research and scientific papers

A convenient method for the preparation of fluorous tin derivatives for the fluorous labeling strategy

(Chemical Equation Presented) A convenient method for the preparation of fluorous aryl stannanes was developed as a means of expanding the general utility of the fluorous labeling strategy (FLS). Following the synthesis of a novel fluorous distannane, a palladium-catalyzed cross-coupling reaction was used to prepare the target compounds from aryl halides. The scope of the reaction was investigated by preparing a small library of model compounds where the reaction yields were similar to those reported for the analogous procedures employing hexamethyl- or hexabutyldistannanes. The utility of the reported methodology was demonstrated through the successful synthesis of fluorous precursors to two established molecular imaging and therapy agents (FIAU, IUdR). These were radiolabeled with iodine-125 and the desired products isolated in high yield and effective specific activity.

Radiosynthesis of [18F]-labelled pro-nucleotides (ProtIDes)

Phosphoramidate pro-nucleotides (ProTides) have revolutionized the field of anti-viral and anti-cancer nucleoside therapy, overcoming the major limitations of nucleoside therapies and achieving clinical and commercial success. Despite the translation of P

NUCLEOSIDES FOR SUPPRESSING OR REDUCING THE DEVELOPMENT OF RESISTANCE IN CYTOSTATIC THERAPY

The invention relates to special nucleosides, for example, a nucleoside of the formula I, wherein R1-R5 are as described herein, and also to drugs which contain these nucleosides. Furthermore, the invention relates to the use of such nucleosides in a method for suppressing or reducing the formation of resistance in the case of cytostatic treatment of a cancer patient.

A general synthesis of 2′-deoxy-2′-[18F]fluoro-1-β-D- arabinofuranosyluracil and its 5-substituted nucleosides

Several 2′-deoxy-2′-[18F]fluoro-1-β-D- arabinofuranosyluracil derivatives have been synthesized. Coupling of 1-bromo-2-deoxy-2-[18F]fluoro-3,5-di-O-benzoyl-α-D- arabinofuranose 2 with protected uracil derivatives 3a-e followed by hydrolysis and high-performance liquid chromatography purification produced the radiolabeled nucleosides 4a-e in 15-30% yield (d. c.), > 99% radiochemical purity and 55.5-103.6 GBq/μmol specific activities. Copyright

Antiviral Nucleosides. A Stereospecific, Total Synthesis of 2'-Fluoro-2'-deoxy-β-D-arabinofuranosyl Nucleosides

A general, total synthesis of (2'-fluoro-2'-deoxy-β-D-arabinofuranosyl)uracils 1a-d is described.A study of the coupling reaction beetwen 3,5-di-O-benzoyl-2-deoxy-2-fluoro-α-D-arabinofuranosyl bromide (7) and silylated pyrimidines 11a-d has resulted in a high overall yield for the five-step stereospecific synthesis of β-nucleosides.

Anti-herpes virus compositions containing 5-substituted 1-2'(deoxy-2-'-substituted-β-d-arabinofuranosyl)pyrimedene nucleosides

Veterinarian composition for the treatment of herpes virus in animals comprising a pyrimidine nucleoside, or veterinarianically acceptable acid addition salte thereof, of the formula STR1 wherein A is OR3, SR3, NR3 R4

5-Substituted 1-(2'-Deoxy-2'-substituted-β-D-arabinofuranosyl)pyrimidine nucleosides

Pyrimidine nucleosides exhibiting anti-viral and anti-tumor effects have the formula STR1 wherein A is OR3, SR3, NR3 R4 or NHacyl wherein R3 and R4 are the same or different and are hydroge