Synthesis and Anti-Hepatitis B Virus Activity of 9-(2-Deoxy-2-fluoro-β-l-arabinofuranosyl)purine Nucleosides

Since the discovery of 2‘-fluoro-5-methyl-β-l-arabinofuranosyluracil (l-FMAU) as a potent anti-HBV and anti-EBV agent, we have studied the structure−activity relationships of 2‘-deoxy-2‘-fluoro-β-l-arabinofuranosylpyrimidine nucleosides as anti-HBV agents. Therefore it is rational to extend this stu...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1997-08, Vol.40 (17), p.2750-2754
Main Authors: Ma, Tianwei, Lin, Ju-Sheng, Newton, M. Gary, Cheng, Yung-Chi, Chu, Chung K
Format: Article
Language:English
Subjects:
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiviral agents
Antiviral Agents - chemical synthesis
Antiviral Agents - pharmacology
Arabinofuranosyluracil - analogs & derivatives
Arabinofuranosyluracil - chemistry
Arabinofuranosyluracil - pharmacology
Biological and medical sciences
Hepatitis B virus - drug effects
Medical sciences
Models, Chemical
Models, Molecular
Pharmacology. Drug treatments
Software
Structure-Activity Relationship
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Summary:Since the discovery of 2‘-fluoro-5-methyl-β-l-arabinofuranosyluracil (l-FMAU) as a potent anti-HBV and anti-EBV agent, we have studied the structure−activity relationships of 2‘-deoxy-2‘-fluoro-β-l-arabinofuranosylpyrimidine nucleosides as anti-HBV agents. Therefore it is rational to extend this study to the purine nucleosides. Thus, 3,5-di-O-benzoyl-2-deoxy-2-fluoro-β-l-arabinofuranosyl bromide (1), which was prepared from l-xylose via a multistep procedure, was coupled with several purines by the sodium salt method. From this general synthesis, 10 purine nucleosides containing the 2-deoxy-2-fluoro-β-l-arabinofuranosyl moiety have been obtained. The anti-HBV activity and toxicity of the synthesized nucleosides were evaluated in HepG2 2.2.15 cells. Among them, the adenine (10) and hypoxanthine (15) derivatives exhibit good in vitro anti-HBV activity (EC50 = 1.5 and 8 μM, respectively) without significant toxicity up to 200 μM.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm970233+