Design and Synthesis of 2‘,3‘-Dideoxy- 2‘,3‘-didehydro-β-l-cytidine (β-l-d4C) and 2‘,3‘-Dideoxy-2‘,3‘-didehydro-β-l-5- fluorocytidine (β-l-Fd4C), Two Exceptionally Potent Inhibitors of Human Hepatitis B Virus (HBV) and Potent Inhibitors of Human Immunodeficiency Virus (HIV) in Vitro

• Published in: Journal of medicinal chemistry 1996-04, Vol.39 (9), p.1757-1759
• Main Authors: Lin, Tai-Shun, Luo, Mei-Zhen, Liu, Mao-Chin, Zhu, Yong-Lian, Gullen, Elizabeth, Dutschman, Ginger E, Cheng, Yung-Chi
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - chemical synthesis; Antiviral Agents - pharmacology; Biological and medical sciences; Drug Design; hepatitis B virus; Hepatitis B virus - drug effects; HIV - drug effects; human immunodeficiency virus; Humans; Medical sciences; Pharmacology. Drug treatments; Zalcitabine - analogs & derivatives; Zalcitabine - chemical synthesis; Zalcitabine - pharmacology
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm950836q

In this communication, we report the synthesis and biological evaluation of beta -L-d4C and beta -L-Fd4C, which show exceptional potent activity against HBV and significant activity against HIV. Since patients receiving long-term, anti-HBV or -HIV nucleoside therapy have experienced delayed toxicity, which may be linked to the drugs inhibition of mitochondrial DNA synthesis, the effect of beta -L-d4C and beta -L-Fd4C in decreasing the mitochondrial DNA content in cells upon long-term exposure to these two drugs was also studied. beta -L-d4C was also independently synthesized by Mansuri et al., however, no physical properties and spectroscopic data were reported. Furthermore, contrary to our results, they reported that this compound has no antiviral activity.