| Identification | Back Directory | [Name]
1-[(2R,3S,4R,5R)-3-Fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-iodopyrimidine-2,4-dione | [CAS]
69123-98-4 | [Synonyms]
FIAU
NSC 678514
FIALURIDINE
5-I-2'-F-dU
Fialuridine(FIAU)
Fluoroiodoarauracil
2'-FLUORO-5-IODOURACIL
5-Iodo-2'-fluoroarauracil
5-Iodo-2'-fluoro-deoxyuridine
2'-Deoxy-2'-fluoro-5-iodouridine
2'-Deoxy-2'-fluoro-5-iodo-D-uridine
5-Iodo-2'-fluoro-2'-deoxy-ara-uridine
Fialuridine
FIAU
2'-Fluoro-5-iodoarauracil
5-Iodo-2'-deoxy-2'-fluoro-beta-D-arabinouridine
2’-fluoro-5-iodo-1-beta-d-arabinofuranosyluracil
1-(2-Deoxy-2-fluoro-β-D-arabinofuranosyl)-5-iodo-
1-(2'FLUORO-2'-DEOXYARABINOFURANOSYL)-5-IODOURACIL
1-(2-DEOXY-2-FLUORO-B-D-ARABINOFURANOSYL)-5-IODOURACIL
5-Iodo-1-(2-fluoro-2-deoxy-β-D-arabinofuranosyl)uracil
1-(2'-Deoxy-2'-fluoro--D-arabinofuranosyl)-5-iodouracil
2'-FLUORO 2'-DEOXY-5-IODOURACIL-BETA-D-ARABINOFURANOSIDE
5-IODO-2'-FLUORO-2'-DEOXY-1-BETA-D-ARABINOFURANOSYLURACIL
1-(2-deoxy-2-fluoro-beta-d-arabinofuranosyl)-5-iodo-uraci
1-(2-deoxy-2-fluoro-beta-d-arabinofuranosyl)-5-iodouracil
1-(2-Deoxy-2-fluoro--D-arabinofuranosyl)-5-iodo-2,4(1H,3H)-pyrimidinedione
2,4(1h,3h)-pyrimidinedione,1-(2-deoxy-2-fluoro-beta-d-arabinofuranosyl)-5-io
2,4(1H,3H)-Pyrimidinedione, 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-iodo-
2,4(1H,3H)-PYRIMIDINEDIONE, 1-(2-DEOXY-2-FLUORO-BETA-D-ARABINOFURANOSYL)-5-IODO-
1-(2-Deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodouracil 5-Iodo-2'-fluoroarauracil
1-[(2R,3S,4R,5R)-3-Fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-iodopyrimidine-2,4-dione | [EINECS(EC#)]
1312995-182-4 | [Molecular Formula]
C9H10FIN2O5 | [MDL Number]
MFCD00866922 | [MOL File]
69123-98-4.mol | [Molecular Weight]
372.09 |
| Chemical Properties | Back Directory | [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. | [Appearance]
Colourless crystals | [Melting point ]
216-217°C | [density ]
2.18±0.1 g/cm3(Predicted) | [storage temp. ]
Refrigerator | [solubility ]
DMSO: soluble5mg/mL, clear (warmed) | [form ]
powder | [pka]
7.94±0.10(Predicted) | [color ]
white to beige | [Merck ]
14,4069 | [InChIKey]
IPVFGAYTKQKGBM-BYPJNBLXSA-N |
| Hazard Information | Back Directory | [Chemical Properties]
Colourless crystals | [Uses]
An antiviral agent; nucleoside analog with antihepatitis B activity | [General Description]
Fialuridine (1-(2-deoxy-2-fluoro-β-d-arabinofuranosyl)-5-iodouracil, or FIAU) is an antiviral agent. It is a thymidine-based nucleoside analogue. | [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. |
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