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Phosphoramidate derivatives of stavudine as inhibitors of HIV: unnatural amino acids may substitute for alanine.
- Source :
-
Antiviral chemistry & chemotherapy [Antivir Chem Chemother] 2000 Mar; Vol. 11 (2), pp. 111-6. - Publication Year :
- 2000
-
Abstract
- Some novel phosphoramidate derivatives of the nucleoside analogue stavudine have been prepared as membrane-soluble prodrugs of the bioactive free phosphate forms. Phenyl phosphates linked via nitrogen to methyl esterified amino acid analogues were studied, where the amino acid was an unnatural alpha-alkyl (or aryl) glycine or an alpha,alpha-dialkyl glycine. All compounds were characterized by a range of spectroscopic, spectrometric and analytical methods and were subjected to in vitro evaluation of their anti-human immunodeficiency virus efficacy. It is notable that certain unnatural amino acid derivatives could substitute for alanine with only a relatively small loss of activity and, moreover, that this activity did not fall-off with increasing alkyl chain length for the C2-C4 mono-alkyl series. These data are further probed by the application of our recently reported 31P-NMR-based carboxyl esterase assay, with informative results.
- Subjects :
- Alanine
Amino Acid Substitution
Amino Acids chemistry
Cell Line drug effects
Cell Line virology
HIV-1 drug effects
HIV-2 drug effects
Humans
Reverse Transcriptase Inhibitors chemistry
Reverse Transcriptase Inhibitors pharmacology
Stavudine pharmacology
Structure-Activity Relationship
Amides chemistry
Anti-HIV Agents chemistry
Anti-HIV Agents pharmacology
Phosphoric Acids chemistry
Stavudine chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 0956-3202
- Volume :
- 11
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Antiviral chemistry & chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 10819435
- Full Text :
- https://doi.org/10.1177/095632020001100203