Bioorganic & Medicinal Chemistry 2010-11-01

Synthesis and in vitro antiviral activities of 3'-fluoro (or chloro) and 2',3'-difluoro 2',3'-dideoxynucleoside analogs against hepatitis B and C viruses.

Naveen C Srivastav, Neeraj Shakya, Michelle Mak, Chao Liang, D Lorne J Tyrrell, Babita Agrawal, Rakesh Kumar, Naveen C. Srivastav, Neeraj Shakya, Michelle Mak, Chao Liang, D. Lorne J. Tyrrell, Babita Agrawal, Rakesh Kumar

文献索引：Bioorg. Med. Chem. 18(21) , 7542-7, (2010)

全文：HTML全文

摘要

Chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) lead to serious liver diseases worldwide. Co-infection with HBV and HCV is very common and is associated with increased risk of liver pathogenesis, liver cancer, and liver failure. Several 5-substituted 3'-fluoro (or chloro) (1-4, 6, 7, 17-19) and 2',3'-difluoro 2',3'-dideoxynucleosides (15 and 16) were synthesized and evaluated for in vitro antiviral activities against duck hepatitis B virus (DHBV), human hepatitis B virus, and hepatitis C virus. Of these compounds 4, 7, 17, and 19 demonstrated moderate anti-HBV activity, and 2, 4, 7, 8, and 19 were weak inhibitors of HCV. Although 5-iodo derivative (7) was most inhibitory against HCV, it exhibited a reduction in cellular RNA levels in Huh-7 cells. The 5-hydroxymethyl-3'-fluoro-2',3'-dideoxyuridine (4) and 1-(3-chloro-2,3-dideoxy-β-d-erythro-pentofuranosyl)-5-fluorouracil (19) provided the most inhibition of both viruses without cytotoxicity.Copyright © 2010 Elsevier Ltd. All rights reserved.