69123-98-4 Usage
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
Different sources of media describe the Uses of 69123-98-4 differently. You can refer to the following data:
1. An antiviral agent; nucleoside analog with antihepatitis B activity
2. Fialuridine has been used in the selection of clones.
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.
Check Digit Verification of cas no
The CAS Registry Mumber 69123-98-4 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 6,9,1,2 and 3 respectively; the second part has 2 digits, 9 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 69123-98:
(7*6)+(6*9)+(5*1)+(4*2)+(3*3)+(2*9)+(1*8)=144
144 % 10 = 4
So 69123-98-4 is a valid CAS Registry Number.
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)
69123-98-4Relevant articles and documents
A convenient method for the preparation of fluorous tin derivatives for the fluorous labeling strategy
McIntee, Jason W.,Sundararajan, Chitra,Donovan, Amanda C.,Kovacs, Michael S.,Capretta, Alfredo,Valliant, John F.
, p. 8236 - 8243 (2008)
(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.
NUCLEOSIDES FOR SUPPRESSING OR REDUCING THE DEVELOPMENT OF RESISTANCE IN CYTOSTATIC THERAPY
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Page/Page column 18, (2010/09/17)
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.
Preparation of 5-Iodo- (FIAU) and 5-Astato-1-(2-deoxy-2-fluoro-&β-D-arabinofuranosyl)uracil (FAAU) by a Halodestannylation Reaction
Vaidyanathan, G.,Affleck, D. J.,Welsh, P.,Li, J.,Schoultz, B. W.,Zalutsky, M. R.
, p. 91 - 93 (2007/10/03)
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