Abstract
A series of purine l-ribonucleosides 2a-2i bearing diverse C-substituents (alkyl, aryl, hetaryl or hydroxymethyl) in the position 6 were prepared by Pd-catalyzed cross-coupling reactions of 6-chloro-9-(2,3,5-tri-O-acetyl-beta-l-ribofuranosyl)purine with the corresponding organometallics followed by deprotection. Unlike their d-ribonucleoside enantiomers that possess strong cytostatic and anti-HCV activity, the l-ribonucleosides were inactive except for 6-benzylpurine nucleoside 2h showing moderate anti-HCV effect in replicon assay. A triphosphate of 2h did not inhibit HCV RNA polymerase.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic 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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Cell Proliferation / drug effects
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Drug Screening Assays, Antitumor
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HL-60 Cells
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HeLa Cells
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Hepacivirus / drug effects
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Humans
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In Vitro Techniques
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Mice
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Microbial Sensitivity Tests
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Molecular Structure
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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
Substances
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Antineoplastic Agents
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Antiviral Agents
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Purine Nucleosides
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Ribonucleosides