Originator
Foscarnet Sodium,AstraZeneca,USA
Definition
ChEBI: Phosphoric acid in which one of the hydroxy groups is replaced by a carboxylic acid group. It is used as the trisodium salt as an antiviral agent in the treatment of cytomegalovirus retinitis (CMV retinitis, an inflamation of the retina that can lead to bl
ndness) and as an alternative to ganciclovir for AIDS patients who require concurrent antiretroviral therapy but are unable to tolerate ganciclovir due to haematological toxicity.
Manufacturing Process
423 g (4.77 mol) of sodium hydroxide is added to 400 ml of water. The
solution is heated to about 50°C and 167 g (0.795 mol) of triethyl
phosphonoformate is added. The reaction mixture is then heated to about
90°C and ethanol formed is distilled off. After about 1 hour at 90-95°C the
reaction mixture is cooled to about 20°C and the product is filtered off. The
yield of trisodium phosphonoformate hexahydrate wet is 248 g.
The wet substance is recrystallized in 570 ml of water by heating to 423 g
(4.77 mol) of sodium hydroxide liquid conc. is added to 400 ml of water. The
solution is heated to about 50°C and 167 g (0.795 mol) of triethyl
phosphonoformate is added at this temperature. The reaction mixture is then
heated to about 90°C and ethanol formed is distilled off. After about 1 hour at
90-95°C the reaction mixture is cooled to about 20°C and the product is
filtered off. The yield of trisodium phosphonoformate hexahydrate wet is 248
g.
The wet substance is recrystallized in 570 ml of water by heating to 90°C in
order to obtain a clear solution and then cooling to about 20°C. After filtration
and washing with 50 ml of water at 18-22°C 187 g (74% of theoretical yield)
of trisodium phosphonoformate hexahydrate is obtained. This substance
contains about 2% free water, which can be eliminated by drying.
Therapeutic Function
Antiviral
Enzyme inhibitor
This pyrophosphate analogue (FWtrisodium salt = 191.95 g/mol; CAS 4428-95-
9), also called foscarnet, exhibits antiherpetic activity. It is a stro+ng inhibitor
of viral reverse transcriptases and viral replication as well as Na/phosphate
cotransporters. Target (s) : adenylyl cyclase; avian myeloblastosis virus
reverse transcriptase; cytomegalovirus DNA polymerase (4-6); DNA-
directed DNA polymerase; DNA polymerase b; DNA
polymerases, viral; duck hepatitis B virus reverse transcriptase
; Epstein-Barr virus DNA polymerase; equine infectious
anemia virus reverse transcriptase; exoribonuclease H; feline
immunodeficiency virus reverse transcriptase; geranyl-diphosphate
cyclase, or bornyl-diphosphate synthase; guanylyl cyclase; HIV-1
reverse transcriptase; human T-lymphotropic
virus type III reverse transcriptase; herpes virus reverse transcriptase
; human hepatitis B virus reverse transcripta+se;
Moloney murine leukemia virus reverse transcriptase; Na-dependent
phosphate transport (32-38); phosphoenolpyruvate carboxylase;
phosphoenolpyruvate mutase; phosphonoacetate hydrolase;
phosphonopyruvate hydrolase; ribonuclease H; RNA-directed
DNA polymerase; simian immunodeficiency virus
reverse transcriptase; and woodchuck hepatitis virus reverse
transcriptase.
