1613590-21-8Relevant articles and documents
Synthesis and Anti-HCV Activity of Sugar-Modified Guanosine Analogues: Discovery of AL-611 as an HCV NS5B Polymerase Inhibitor for the Treatment of Chronic Hepatitis C
Wang, Guangyi,Dyatkina, Natalia,Prhavc, Marija,Williams, Caroline,Serebryany, Vladimir,Hu, Yujian,Huang, Yongfei,Wu, Xiangyang,Chen, Tongqian,Huang, Wensheng,Rajwanshi, Vivek K.,Deval, Jerome,Fung, Amy,Jin, Zhinan,Stoycheva, Antitsa,Shaw, Kenneth,Gupta, Kusum,Tam, Yuen,Jekle, Andreas,Smith, David B.,Beigelman, Leonid
, p. 10380 - 10395 (2020/11/02)
Chronic hepatitis C (CHC) is a major liver disease caused by the hepatitis C virus. The current standard of care for CHC can achieve cure rates above 95%; however, the drugs in current use are administered for a period of 8-16 weeks. A combination of safe and effective drugs with a shorter treatment period is highly desirable. We report synthesis and biological evaluation of a series of 2′,3′- and 2′,4′-substituted guanosine nucleotide analogues. Their triphosphates exhibited potent inhibition of the HCV NS5B polymerase with IC50 as low as 0.13 μM. In the HCV replicon assay, the phosphoramidate prodrugs of these analogues demonstrated excellent activity with EC50 values as low as 5 nM. A lead compound AL-611 showed high levels of the nucleoside 5′-triphosphate in vitro in primary human hepatocytes and in vivo in dog liver following oral administration.
SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF
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, (2016/03/11)
Disclosed herein are nucleosides, nucleotide analogs, methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a Filoviridae virus infection with one or more nucleosides and/or nucleotide analogs.
SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF
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, (2014/07/08)
Disclosed herein are nucleotide analogs, methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a HCV infection with one or more nucleotide analogs.
