Abstract
A series of 80 7-(het)aryl- and 7-ethynyl-7-deazapurine ribonucleosides bearing a methoxy, methylsulfanyl, methylamino, dimethylamino, methyl, or oxo group at position 6, or 2,6-disubstituted derivatives bearing a methyl or amino group at position 2, were prepared, and the biological activity of the compounds was studied and compared with that of the parent 7-(het)aryl-7-deazaadenosine series. Several of the compounds, in particular 6-substituted 7-deazapurine derivatives bearing a furyl or ethynyl group at position 7, were significantly cytotoxic at low nanomolar concentrations whereas most were much less potent or inactive. Promising activity was observed with some compounds against Mycobacterium bovis and also against hepatitis C virus in a replicon assay.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Bacterial Agents / chemical synthesis*
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / pharmacology
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Antitubercular Agents / chemical synthesis
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Antitubercular Agents / chemistry
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Antitubercular Agents / pharmacology
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Antiviral Agents / chemical synthesis*
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Antiviral Agents / chemistry
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Antiviral Agents / pharmacology
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Cell Line, Tumor
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Cytostatic Agents / chemical synthesis*
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Cytostatic Agents / chemistry
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Cytostatic Agents / pharmacology
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Cytotoxins / chemical synthesis
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Cytotoxins / chemistry
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Cytotoxins / pharmacology
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Hepacivirus / drug effects*
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Hepacivirus / physiology
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Humans
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Mycobacterium bovis / drug effects
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Purine Nucleosides / chemical synthesis*
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Purine Nucleosides / chemistry
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Purine Nucleosides / pharmacology
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Ribonucleosides / chemical synthesis*
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Ribonucleosides / chemistry
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Ribonucleosides / pharmacology
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Structure-Activity Relationship
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Virus Replication / drug effects
Substances
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Anti-Bacterial Agents
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Antitubercular Agents
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Antiviral Agents
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Cytostatic Agents
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Cytotoxins
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Purine Nucleosides
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Ribonucleosides