- Acyloxymethyl and 4-acyloxybenzyl diester prodrugs of phosphonoformate
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Sodium pivaloyloxymethyl (pivaloyloxymethoxycarbonyl)phosphonate 4, sodium 4-acyloxybenzyl phenoxycarbonylphosphonates 14a-c and sodium 4-acyloxybenzyl benzyloxycarbonylphosphonates 15a,b have been prepared as bioreversible prodrugs of the antiviral phosphonoformate 1. Their hydrolyses, in vivo systemic bioavailability and antiviral activity are reported. Of the compounds evaluated 4 was the best prodrug.
- Briggs, Andrew D.,Camplo, Michel,Freeman, Sally,Lundstroem, Jan,Pring, Brian G.
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p. 14937 - 14950
(2007/10/03)
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- Synthesis, Properties and Structure of New 1,1-Diphosphonic Acids
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The synthesis of 3-tert-alkyl-3-oxo-1-aminopropane-1,1-diphosphonic acids and of 3-tert-alkyl-3-oxo-prop-1-ene-1,1-diphosphonic acids as two new groups of metal complexing agents and their chemical properties are described.Evidence is given for their suggested structures.In addition, the first known example of a diphosphonic acid with a cyano group attached to the geminal carbon atom was prepared from 3-oxo-1-aminoalkane-1,1-diphosphonic acids and 3-tert-alkyl-3-oxo-1-hydroxypropane-1,1-diphosphonic acids from 3-oxo-1-aminopropane-1,1-diphosphonic acids. - Keywords: 3-tert-Alkyl-3-oxo-1-aminopropane-1,1-diphosphonic Acids, 3-tert-Alkyl-3-oxo-1-hydroxypropane-1,1-diphosphonic Acids, 3-tert-Alkyl-3-oxo-prop-1-ene-1,1-diphosphonic Acids, Diphosphonocyanohydrin, Preparation
- Blum, Helmut
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- Method for combating virus infection
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A method for the selective treatment of virus infections in animals and man comprising administering to a host so infected a therapeutically effective amount of phosphonoformic acid or a physiologically acceptable salt thereof.
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- Synthesis of esters of phosphonoformic acid and their antiherpes activity
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Aliphatic and aromatic mono-, di-, and triesters of phosphonoformic (foscarnet) were synthesized. The triesters were prepared by the Michaelis-Arbuzov reaction and were hydrolyzed to di- and monoesters. The compounds were tested for antiviral activity on isolated herpes simplex virus type 1 (HSV-1) DNA polymerase, in a HSV-1 plaque reduction assay, and on a cutaneous HSV-1 infection in guinea pigs. None of the esters inhibited the activity of isolated HSV-1 polymerases. Monoesters with a free carboxylic group and diesters with an aromatic carboxylic ester function were active against the cutaneous herpesa infection. Mono- and diesters with an aromatic phosphonic ester group also showed activity in the plaque-reduction assay. However, mono- and diesters with aliphatic carboxylic ester groups were inactive in all test systems. The results show that all three acidic groups of phosphonoformic acid must be free in order to get antiviral activity at the enzyme level. However, certain esters of this acid may be biotransformed to the acid itself to give antiherpes activity.
- Noren,Helgstrand,Johansson,Misiorny,Stening
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p. 264 - 270
(2007/10/02)
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- Method for combating virus infection
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A method for the selective treatment of virus infections in animals and man and a method of treating cancer caused by viruses, comprising administering to a host so infected a therapeutically effective amount of phosphonoformic acid or a physiologically acceptable salt thereof.
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- METHOD FOR COMBATING VIRUS INFECTIONS
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A method for the selective treatment of virus infections in animals and man, comprising administering to a host so infected a therapeutically effective amount of phosphonoformic acid or a physiologically acceptable salt thereof
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