Abstract
We report the synthesis of 2',3'-didehydro-2',3'-dideoxyuridine (d4U) and 2',3'-dideoxyuridine (ddU) phosphoramidate 'ProTide' derivatives and their evaluation against HIV-1 and HIV-2. In addition, we conducted molecular modeling studies on both d4U and ddU monophosphates to investigate their second phosphorylation process. The findings from the modeling studies provide compelling evidence for the lack of anti-HIV activity of d4U phosphoramidates, in contrast with the corresponding ddU phosphoramidates.
MeSH terms
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Amides / chemistry*
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Anti-HIV Agents / chemical synthesis*
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Anti-HIV Agents / chemistry
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Chemistry, Pharmaceutical / methods*
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Dideoxynucleosides / chemical synthesis*
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Dideoxynucleosides / chemistry*
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Drug Design
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HIV-1 / metabolism
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HIV-2 / metabolism
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Models, Chemical
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Models, Molecular
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Nucleoside-Phosphate Kinase / chemistry
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Nucleosides / chemistry
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Phosphates / chemistry
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Phosphoric Acids / chemistry*
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Phosphorylation
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Thymidine Monophosphate / chemistry
Substances
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Amides
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Anti-HIV Agents
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Dideoxynucleosides
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Nucleosides
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Phosphates
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Phosphoric Acids
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Thymidine Monophosphate
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2',3'-didehydro-2',3'-dideoxyuridine
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2',3'-dideoxyuridine
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phosphoramidic acid
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Nucleoside-Phosphate Kinase
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dTMP kinase