Literature DB >> 31514570

Synthesis and evaluation of the anti-hepatitis B virus activity of 4'-Azido-thymidine analogs and 4'-Azido-2'-deoxy-5-methylcytidine analogs: structural insights for the development of a novel anti-HBV agent.

Kengo Onitsuka1, Ryoh Tokuda1, Nobuyo Kuwata-Higashi2, Hiroki Kumamoto3, Manabu Aoki4, Masayuki Amano5, Satoru Kohgo2, Debananda Das4, Kazuhiro Haraguchi3, Hiroaki Mitsuya2,4,5, Shuhei Imoto1.   

Abstract

Hepatitis B virus (HBV) infection is a major worldwide health problem that requires the development of improved antiviral therapies. Here, a series of 4'-Azido-thymidine/4'-Azido-2'-deoxy-5-methylcytidine derivatives (6, 10-15) were synthesized, and their anti-HBV activities evaluated. Compounds 10-15 were synthesized via an SNAr reaction of 18, in which the 4-position of the thymine moiety was activated as the 2,4,6-triisopropylbenzenesulfonate. Compounds 11-15 showed no antiviral activity. However, 4'-Azido thymidine (6) and 4'-Azido-2'-deoxy-5-methylcytidine (10) displayed significant anti-HBV activity (EC50 = 0.63 and 5.99 µM, respectively) with no detectable cytotoxicity against MT-2 cells up to 100 µM.

Entities:  

Keywords:  4′-azido nucleoside; Anti-HBV nucleoside; modified pyrimidines

Mesh：

Substances：

Year:  2019        PMID： 31514570      PMCID： PMC8191380          DOI： 10.1080/15257770.2019.1664749

Source DB:  PubMed          Journal:  Nucleosides Nucleotides Nucleic Acids        ISSN： 1525-7770            Impact factor:   1.381


  22 in total

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