Abstract
A series of nucleoside phosphonate reverse transcriptase (RT) inhibitors have been synthesized and their anti-HIV activity and resistance profiles evaluated. The most potent analog [5-(6-amino-purin-9-yl)-2,5-dihydro-furan-2-yloxymethyl]-phosphonic acid (d4AP) demonstrated a HIV EC(50)=2.1 microM, and the most favorable resistance profile against HIV-1 variants with K65R, M184V or multiple thymidine analog mutations in RT.
MeSH terms
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Adenine / analogs & derivatives
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Adenine / pharmacology
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Anti-HIV Agents / chemical synthesis
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Anti-HIV Agents / chemistry
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Anti-HIV Agents / pharmacokinetics
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Anti-HIV Agents / pharmacology
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Combinatorial Chemistry Techniques
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Drug Design
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HIV / drug effects*
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HIV / genetics*
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Molecular Structure
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Nucleosides* / chemical synthesis
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Nucleosides* / chemistry
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Nucleosides* / pharmacokinetics
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Nucleosides* / pharmacology
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Organophosphonates* / chemical synthesis
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Organophosphonates* / chemistry
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Organophosphonates* / pharmacokinetics
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Organophosphonates* / pharmacology
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Reverse Transcriptase Inhibitors* / chemical synthesis
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Reverse Transcriptase Inhibitors* / chemistry
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Reverse Transcriptase Inhibitors* / pharmacokinetics
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Reverse Transcriptase Inhibitors* / pharmacology
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Structure-Activity Relationship
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Tenofovir
Substances
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(5-(6-amino-purin-9-yl)-2,5-dihydrofuran-2-yloxymethyl)phosphonic acid
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Anti-HIV Agents
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Nucleosides
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Organophosphonates
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Reverse Transcriptase Inhibitors
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Tenofovir
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Adenine