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糖修饰的嘧啶并[4,5-]吲哚核苷：合成与抗病毒活性

Sugar modified pyrimido[4,5-]indole nucleosides: synthesis and antiviral activity.

作者信息

Konč Juraj, Tichý Michal, Pohl Radek, Hodek Jan, Džubák Petr, Hajdúch Marián, Hocek Michal

机构信息

Institute of Organic Chemistry and Biochemistry , Czech Academy of Sciences , Flemingovo nam. 2 , CZ-16610 Prague 6 , Czech Republic . Email:

Institute of Molecular and Translational Medicine , Palacky University and University Hospital in Olomouc , Faculty of Medicine and Dentistry , Hněvotínská 5 , CZ-775 15 Olomouc , Czech Republic.

出版信息

Medchemcomm. 2017 Aug 25;8(9):1856-1862. doi: 10.1039/c7md00319f. eCollection 2017 Sep 1.

DOI:10.1039/c7md00319f
PMID:30108897
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6084004/
Abstract

Three types of sugar modified pyrimido[4,5-]indole nucleosides (2'-deoxy-2'-fluororibo-, 2'-deoxy-2'-fluoroarabino- and arabinonucleosides) were synthesized by glycosylation of 4,6-dichloropyrimido[4,5-]indole followed by modification of sugar moiety and introduction of substituents into position 4 by cross-coupling reactions or nucleophilic substitutions. Some 2'-fluororibo- and 2'-fluoroarabinonucleosides displayed interesting anti-HCV activities (IC = 1.6-20 μM) and the latter compounds also some anti-dengue activities (IC = 10.8-40 μM).

摘要

通过4,6-二氯嘧啶并[4,5-]吲哚的糖基化反应，随后对糖部分进行修饰，并通过交叉偶联反应或亲核取代反应在4位引入取代基，合成了三种糖修饰的嘧啶并[4,5-]吲哚核苷（2'-脱氧-2'-氟核糖核苷、2'-脱氧-2'-氟阿拉伯糖核苷和阿拉伯糖核苷）。一些2'-氟核糖核苷和2'-氟阿拉伯糖核苷表现出有趣的抗丙型肝炎病毒活性（IC = 1.6 - 20 μM），后一类化合物还具有一些抗登革热活性（IC = 10.8 - 40 μM）。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9dd/6084004/cec169f91705/c7md00319f-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9dd/6084004/53aff4b86fdd/c7md00319f-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9dd/6084004/fcb8a99faab5/c7md00319f-s1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9dd/6084004/8f7b7117f3de/c7md00319f-s2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9dd/6084004/3e48dc3df41d/c7md00319f-s3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9dd/6084004/9283395b2154/c7md00319f-s4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9dd/6084004/cec169f91705/c7md00319f-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9dd/6084004/53aff4b86fdd/c7md00319f-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9dd/6084004/fcb8a99faab5/c7md00319f-s1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9dd/6084004/8f7b7117f3de/c7md00319f-s2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9dd/6084004/3e48dc3df41d/c7md00319f-s3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9dd/6084004/9283395b2154/c7md00319f-s4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9dd/6084004/cec169f91705/c7md00319f-f2.jpg

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2
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J Med Chem. 2017 Mar 9;60(5):1648-1661. doi: 10.1021/acs.jmedchem.6b01594. Epub 2017 Feb 14.
3
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4
In silico DFT study, molecular docking, and ADMET predictions of cytidine analogs with antimicrobial and anticancer properties.具有抗菌和抗癌特性的胞苷类似物的计算机辅助密度泛函理论（DFT）研究、分子对接及药物代谢动力学/药物毒性（ADMET）预测
In Silico Pharmacol. 2021 Jul 6;9(1):42. doi: 10.1007/s40203-021-00102-0. eCollection 2021.
5
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Approved Antiviral Drugs over the Past 50 Years.
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6
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8
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9
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10
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J Infect Dis. 2014 Mar 1;209(5):668-75. doi: 10.1093/infdis/jit562. Epub 2013 Oct 23.