Famciclovir CAS NO.104227-87-4

Product Name:    Famciclovir
Synonyms:    Famciclover;Amciclovir;FAMCICLOVIR;[2-(acetyloxymethyl)-4-(2-aminopurin-9-yl)-butyl] acetate;2-[2-(2-AMINO-9H-PURIN-9-YL)ETHYL]-1,3-PROPANEDIOL, DIACETATE ESTER;famcyclovir;[2-(acetyloxymethyl)-4-(2-aminopurin-9-yl)butyl] ethanoate;Famciclovir, 98%, Antiviral guanosine analog
CAS:    104227-87-4
MF:    C14H19N5O4
MW:    321.33
EINECS:    630-411-6
Mol File:    104227-87-4.mol                                 

Melting point     102-104°C
Boiling point     550.2±60.0 °C(Predicted)
density     1.40±0.1 g/cm3(Predicted)
storage temp.     2-8°C
solubility     DMSO: ≥10mg/mL
pka    4.00±0.10(Predicted)
form     solid
λmax    310nm(EtOH)(lit.)
InChIKey    GGXKWVWZWMLJEH-UHFFFAOYSA-N
CAS DataBase Reference    104227-87-4(CAS DataBase Reference)
Safety Information
Hazard Codes     T
Risk Statements     20/21/22-45-61
Safety Statements     36/37/39-45-53-24/25
WGK Germany     3
RTECS     TY3164000
HS Code     29335990
Hazardous Substances Data    104227-87-4(Hazardous Substances Data)
MSDS Information
Provider    Language
Famciclovir    English
Famciclovir Usage And Synthesis
Description    Famciclovir, an effective oral prodrug of the antiviral penciclovir, was launched in the UK and shortly after in the U.S.A. for the treatment of shingles (herpes zoster). As the diacetyl ester of the 6-deoxy- penciclovir, famciclovir has significantly improved oral absorption. It is converted to penciclovir in vivo with a bioavailability of 41 % in rats. Penciclovir is phosphorylated, and hence activated onty in herpesvirus infected cells. This stable metabolite, penciclovir-triphosphate, is a strong inhibitor of herpesvirus DNA polymerases and of viral DNA synthesis with long lasting effects. The high selectivity of famciclovir/penciclovir to herpes family of viruses and their rather low toxicity may make this agent superior to other existing drugs.
Chemical Properties    Off-White Powder
Originator    SmlthKline Beecham (United Kingdom)
Uses    Used as an antiviral. Prodrug of Penciclovir (P221500).
Uses    sterol absorption inhibitor.
Famciclovir Tablets
Famciclovir (Famvir) a synthetic acyclic purine analog derived from guanine. It is the diacetyl ester (prodrug) of penciclovir, which exhibits no antiviral activity until hydrolyzed to penciclovir and its active metabolites. It is indicated for the management of acute herpes zoster infections. It has been shown to relieve acute symptoms as well as to shorten the duration of postherpetic neuralgia. It is also used for the treatment or suppression of recurrent episodes of genital herpes in immunocompetent patients and in the treatment of recurrent herpes simplex types 1 and 2 infections in patients with human immunodeficiency virus.
Definition    ChEBI: 2-Amino-9H-purine in which the hydrogen at position 9 is substituted by a 4-acetoxy-3-(acetoxymethyl)but-1-yl group. A prodrug of the antiviral penciclovir, it is used for the treatment of acute herpes zoster (shingles), for the treatmen or suppression of recurrent genital herpes in immunocompetent patients and for the treatment of recurrent mucocutaneous herpes simplex infections in HIV infected patients.
Indications    Famciclovir (Famvir) is the diacetyl ester prodrug of the acyclic guanosine analogue 6-deoxypenciclovir (Denavir).
Manufacturing Process    A suspension 1.0 mmol of 9-(4-acetoxy-3-acetoxymethylbut-1-yl)-2-amino-6- chloropurine (was synthesized from 2-amino-6-chloropurine and acetic acid 2- acetoxymethyl-4-hydroxybutyl ester) and 400 mmol 10% palladium-oncharcoal in methanol containing ammonium formate was heated under reflux for 30 min. The mixture was allowed to cool, filtered and the solvent removed. The residue was taken up in water and solution extracted twice with chloroform. The organic layers were combined, dried (magnesium sulfate) and the solvent removed to afford 9-(4-acetoxy-3-acetoxymethylbut-1-yl)-2- amino-6-purine, yield 90%, m.p. 102-104°C.
Brand name    Famvir (Novartis);Famvlr.
Therapeutic Function    Antiviral
General Description    Famciclovir is a diacetyl prodrug of penciclovir.As a prodrug,it lacks antiviral activity. Penciclovir, 9-[4-hydroxy-3-hydroxymethylbut-1-yl] guanine, is an acyclic guanine nucleoside analog. The structure is similar to that of acyclovir,except in penciclovir, a side chain oxygen has beenreplaced by a carbon atom and an extra hydroxymethylgroup is present.
VSV-infected cells, penciclovir is first phosphorylated byviral thymidine kinase41 and then further elaborated to thetriphosphate by host cell kinases. Penciclovir triphosphate isa competitive inhibitor of viral DNA polymerase. The pharmacokineticparameters of penciclovir are quite different fromthose of acyclovir. Although penciclovir triphosphate is about100-fold less potent in inhibiting viral DNA polymerase thanacyclovir triphosphate, it is present in the tissues for longerperiods and in much higher concentrations than acyclovir.
Mechanism of action    Famciclovir is a synthetic purine nucleoside analogue related to guanine. It is the diacetyl 6-deoxy ester of penciclovir, which is structurally related to ganciclovir. Its pharmacological and microbiological activities are similar to those of acyclovir. Famciclovir is a prodrug of penciclovir, which is formed in vivo by hydrolysis of the acetyl groups and oxidation at the 6-position by mixed function oxidases. Penciclovir and its metabolite penciclovir triphosphate possess antiviral activity resulting from inhibition of viral DNA polymerase.
Pharmacology    Famciclovir (Famvir) undergoes extensive first-pass metabolism to penciclovir after oral administration. Penciclovir is another nucleoside analog that has a mechanism of action similar to that of acyclovir. Compared with oral acyclovir, famciclovir has improved bioavailability as well as a significantly prolonged intracellular half-life, allowing for less frequent dosing. Valacyclovir and famciclovir are similar in their high absorption, bioavailability, renal elimination, minimal drug interaction profiles, safety profiles, and efficacy.
Pharmacokinetics    Famciclovir can be given with or without food. The most common adverse effects are headache and GI disturbances. Concomitant use of famciclovir with probenecid results in increased plasma concentrations of penciclovir. The recommended dose of famciclovir is 500 mg every 8 hours for 7 days. The absolute bioavailability of famciclovir is 77%, and the area under plasma concentration–time curve (AUC) is 86 μg/mL. Famciclovir with digoxin increased plasma concentration of digoxin to 19% as compared to digoxin given alone.
Clinical Use    Famciclovir is indicated for the treatment of acute herpes zoster (shingles); it is at least as effective in reducing pain and healing time. Famciclovir is generally as effective as acyclovir in the treatment of HSV. In immunocompetent patients, famciclovir is approved for the treatment and prophylaxis of recurrent genital herpes. For HIV-infected individuals, famciclovir is approved for the treatment of all recurrent mucocutaneous HSV infections.
Side effects    Famciclovir may interact with probenecid or other drugs eliminated by renal tubular secretion. This interaction may result in increased blood levels of penciclovir or other agents.
Veterinary Drugs and Treatments    Famciclovir may be of benefit in treating feline herpes infections.
Famciclovir Preparation Products And Raw materials
Raw materials    Propylene glycol-->Guanine-->6-Chloroguanine-->2-Amino-6-iodopurine-->Triethylmethylammonium chloride-->2-Aminopurine-->1,2-Propyleneglycol diacetate-->Palladium hydroxide-->Ammonium formate