Phosphoramidate Derivatives of AZT as Inhibitors of HIV: Studies on the Carboxyl Terminus
- 1 April 1993
- journal article
- Published by SAGE Publications in Antiviral Chemistry and Chemotherapy
- Vol. 4 (2) , 97-101
- https://doi.org/10.1177/095632029300400204
Abstract
Novel phosphoramidate derivatives of the anti-HIV nucleoside analogue AZT have been prepared by phosphorochloridate chemistry. These materials carry carboxy-protected, amino acids, and are designed to act as membrane-soluble prodrugs of the bio-active free nucleotides. In vitro evaluation revealed the compounds to have a pronounced, selective antiviral activity. In particular, variation in the carboxy terminus region is studied. For alkyl phosphates small changes in the structure of the amino ester lead to marked changes in biological activity. However, for analogous aryl phosphates there is little dependence on the structure of the ester. This suggests a different mechanism of action for these two categories of phosphate prodrug.Keywords
This publication has 14 references indexed in Scilit:
- Comparison of Antiviral Effects of Zidovudine Phosphoramidate and Phosphorodiamidate Derivatives against HIV and ULVin vitroAntiviral Chemistry and Chemotherapy, 1992
- Synthesis and anti-HIV activity of some haloalkyl phosphoramidate derivatives of 3′-azido-3′-deoxythymidine (AZT): potent activity of the trichloroethyl methoxyalaninyl compoundAntiviral Research, 1991
- Synthesis and anti-HIV evaluation of some phosphoramidate derivatives of AZT: Studies on the effect of chain elongation on biological activityAntiviral Research, 1990
- Synthesis and anti-HIV Activity of Some Novel Substituted Dialkyl Phosphate Derivatives of AZT and ddCydAntiviral Chemistry and Chemotherapy, 1990
- Synthesis and Evaluation of Some Novel Phosphoramidate Derivatives of 3′-Azido-3′-Deoxythymidine (AZT) as Anti-HIV CompoundsAntiviral Chemistry and Chemotherapy, 1990
- Novel phosphate derivatives of zidovudine as anti-HIV compoundsAIDS, 1990
- Synthesis of Some Novel Dialkyl Phosphate Derivatives of 3′-Modified Nucleosides as Potential Anti-AIDS DrugsAntiviral Chemistry and Chemotherapy, 1990
- Synthesis and biological evaluation of some phosphate triester derivatives of the anti-cancer drug AraCNucleic Acids Research, 1989
- Synthesis and biological evaluation of some phosphate triester derivatives of the anti-viral drug AraANucleic Acids Research, 1989
- Comparison of antigen capture assays against HIV-1 in evaluating antiviral compoundsAIDS, 1989