Fialuridine

Fialuridine Basic information

Product Name:

Fialuridine

Synonyms:

1-[(2R,3S,4R,5R)-3-Fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-iodopyrimidine-2,4-dione;2,4(1H,3H)-Pyrimidinedione, 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-iodo-;1-(2-Deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodouracil 5-Iodo-2'-fluoroarauracil;Fluoroiodoarauracil;NSC 678514;1-(2-Deoxy-2-fluoro--D-arabinofuranosyl)-5-iodo-2,4(1H,3H)-pyrimidinedione;1-(2'-Deoxy-2'-fluoro--D-arabinofuranosyl)-5-iodouracil;5-Iodo-2'-fluoroarauracil

CAS:

MF:

C9H10FIN2O5

MW:

372.09

EINECS:

1312995-182-4

Product Categories:

Anti-virals;Bases & Related Reagents;Intermediates & Fine Chemicals;Nucleotides;Pharmaceuticals

Mol File:

69123-98-4.mol

 

Fialuridine Chemical Properties

Melting point 

216-217°C

storage temp. 

Refrigerator

solubility 

DMSO: soluble5mg/mL, clear (warmed)

form 

powder

color 

white to beige

Merck 

14,4069

 

Safety Information

Safety Statements 

24/25

WGK Germany 

3

RTECS 

YQ9512500

HS Code 

29349990

MSDS Information

 

Fialuridine Usage And Synthesis

Description

Fialuridine (FIAU) is one of a series of 2'-fluoro-substituted arabinosyl pyrimidine nucleosides that have demonstrated potent antiviral activities against a number of clinically important viruses, including hepatitis B virus (HBV). Analogs of FIAU have been shown to inhibit viral replication in the woodchuck and duck models of HBV infection. Although the mechanism of the anti-HBV activity is not well understood, evidence suggests that the triphosphate analog of FIAU is a potent inhibitor of HBV DNA polymerase activity. During early clinical investigation FIAU showed much promise as an antiHBV drug because it markedly reduced the level of HBV DNA in the serum of patients with chronic hepatitis B. However, clinical trials were terminated after adverse events occurred following oral administration of FIAU (0.1 and 0.25 mg/kg of body weight per day) for more than 2 months. The mechanism of the unexpected delayed toxicity is unresolved.

Chemical Properties

Colourless crystals

Uses

An antiviral agent; nucleoside analog with antihepatitis B activity

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.