Chemical and enzymatic stability of amino acid derived phosphoramidates of antiviral nucleoside 5'-monophosphates bearing a biodegradable protecting group.
Org Biomol Chem
; 8(9): 2131-41, 2010 May 07.
Article
em En
| MEDLINE
| ID: mdl-20401390
ABSTRACT
Ribavirin and 2'-O-methylcytidine 5'-phosphoramidates derived from L-alanine methyl ester bearing either an O-phenyl or a biodegradable O-[3-(acetyloxy)-2,2-bis(ethoxycarbonyl)propyl] or O-[3-(acetyloxymethoxy)-2,2-bis(ethoxycarbonyl)propyl] protecting group were prepared. The kinetics of the deprotection of these pro-drugs by porcine liver esterase and by a whole cell extract of human prostate carcinoma was studied by HPLC-ESI-MS/MS. The 3-(acetyloxymethoxy)-2,2-bis(ethoxycarbonyl)propyl and 3-(acetyloxy)-2,2-bis(ethoxycarbonyl)propyl groups were readily removed releasing the l-alanine methyl ester phosphoramidate nucleotide, the deprotection of the 3-(acetyloxymethoxy) derivative being approximately 20 times faster. The chemical stability of the 2'-O-methylcytidine pro-drugs was additionally determined over a pH range from 7.5 to 10.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Antivirais
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Ácidos Fosfóricos
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Neoplasias da Próstata
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Ribavirina
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Monofosfato de Citidina
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Alanina
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Esterases
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Amidas
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Malonatos
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Acetatos
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article