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

• Published in: Journal of medicinal chemistry Vol. 40; no. 17; pp. 2750 - 2754
• Main Authors: Ma, Tianwei, Lin, Ju-Sheng, Newton, M. Gary, Cheng, Yung-Chi, Chu, Chung K
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 15.08.1997; Amer Chemical Soc
• 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; Chemistry, Medicinal; Hepatitis B virus - drug effects; Life Sciences & Biomedicine; Medical sciences; Models, Chemical; Models, Molecular; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Science & Technology; Software; Structure-Activity Relationship; ANALOGS; DNA; Virus; Purine nucleoside; Structure activity relation; Hepadnaviridae; Antiviral; Fluorine Organic compounds; Hepatitis B virus; Chemical synthesis; In vitro
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm970233+

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.