Design, synthesis, and biological evaluation of new 2′-deoxy-2′-fluoro-4′-triazole cytidine nucleosides as potent antiviral agents

被引：49

作者：

Wu, Jie ^{[1
]}

Yu, Wenquan ^{[1
]}

Fu, Leixia ^{[1
]}

He, Wu ^{[1
]}

Wang, Yao ^{[1
]}

Chai, Baoshan ^{[1
]}

Song, Chuanjun ^{[1
]}

Chang, Junbiao ^{[1
]}

机构：

[1] Zhengzhou Univ, Coll Chem & Mol Engn, Zhengzhou 450001, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 63卷

基金：

美国国家科学基金会; 中国博士后科学基金;

关键词：

2 '-Deoxy-2 '-fluoro-4 '-triazole nucleosides; Anti-HIV activity; Nucleoside reverse transcriptase inhibitor (NRTI); Anti-HBV activity; HEPATITIS-B-VIRUS; CLICK CHEMISTRY; CHEMICAL-SYNTHESIS; HIV-1; PROTEASE; C-NUCLEOSIDES; IN-VITRO; ANALOGS; TYPE-1; FUNCTIONALIZATION; OLIGONUCLEOTIDES;

D O I：

10.1016/j.ejmech.2013.02.042

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 4'-[1,2,3]triazole-2'-deoxy-2'-fluoro-beta-D-arabinofuranosylcytosines (9-17) were prepared by Cu(I)-mediated [3 + 2] cycloaddition reactions (CuAAC) of 1-(4'-azido-2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)cytosine (1) with appropriate alkynes in good yields. Their structures were fully established by H-1 NMR, C-13 NMR, HRMS, and elemental analysis. Most of these nucleoside analogs exhibited potent anti-HIV-1 activity with no cytotoxicity observed at the highest tested concentration up to 25 mu M. Among them, compounds 9, 10 and 13 exhibited extremely potent antiviral activity, thus had a great potential for further development as novel nucleoside reverse transcriptase inhibitors (NRTIs) for the treatment of HIV-1 infection. Besides, the anti-HBV activity of compounds 10, 11 and 17 had been investigated. (C) 2013 Elsevier Masson SAS. All rights reserved.

引用

页码：739 / 745

页数：7

共 67 条

[1] Click Chemistry: 1,2,3-Triazoles as Pharmacophores
Agalave, Sandip G.
Maujan, Suleman R.
Pore, Vandana S.
[J]. CHEMISTRY-AN ASIAN JOURNAL, 2011, 6 (10) : 2696 - 2718
[2] Cu(I)-Catalyzed Huisgen Azide-Alkyne 1,3-Dipolar Cycloaddition Reaction in Nucleoside, Nucleotide, and Oligonucleotide Chemistry
Amblard, Franck
Cho, Jong Hyun
Schinazi, Raymond F.
[J]. CHEMICAL REVIEWS, 2009, 109 (09) : 4207 - 4220
[3] 1,2,3-triazole as a peptide surrogate in the rapid synthesis of HIV-1 protease inhibitors
Brik, A
Alexandratos, J
Lin, YC
Elder, JH
Olson, AJ
Wlodawer, A
Goodsell, DS
Wong, CH
[J]. CHEMBIOCHEM, 2005, 6 (07) : 1167 - +
[4] Study of copper(I) catalysts for the synthesis of carbanucleosides via azide-alkyne 1,3-dipolar cycloaddition
Broggi, Julie
Diez-Gonzalez, Silvia
Petersen, Jeffrey L.
Berteina-Raboin, Sabine
Nolan, Steven P.
Agrofoglio, Luigi A.
[J]. SYNTHESIS-STUTTGART, 2008, (01): : 141 - 148
[5] CARMICHAEL J, 1987, CANCER RES, V47, P943
[6] CHEMISTRY AND ANTIVIRAL ACTIVITIES OF ACYCLONUCLEOSIDES
CHU, CK
CUTLER, SJ
[J]. JOURNAL OF HETEROCYCLIC CHEMISTRY, 1986, 23 (02) : 289 - 319
[7] Synthesis of 2′,3′-dideoxy-3′-fluoro-L-ribonucleosides as potential antiviral agents from D-sorbitol
Chun, BK
Schinazi, RF
Cheng, YC
Chu, CK
[J]. CARBOHYDRATE RESEARCH, 2000, 328 (01) : 49 - 59
[8] VPR IS REQUIRED FOR EFFICIENT REPLICATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN MONONUCLEAR PHAGOCYTES
CONNOR, RI
CHEN, BK
CHOE, S
LANDAU, NR
[J]. VIROLOGY, 1995, 206 (02) : 935 - 944
[9] 2-Triazole-substituted adenosines:: A new class of selective A3 adenosine receptor agonists, partial agonists, and antagonists
Cosyn, Liesbet
Palaniappan, Krishnan K.
Kim, Soo-Kyung
Duong, Heng T.
Gao, Zhan-Guo
Jacobson, Kenneth A.
Van Calenbergh, Serge
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (25) : 7373 - 7383
[10] Anti-hepatitis B Virus Activities of Cinobufacini and Its Active Components Bufalin and Cinobufagin in HepG2.2.15 Cells
Cui, Xiaoyan
Inagaki, Yoshinori
Xu, Huanli
Wang, Dongliang
Qi, Fanghua
Kokudo, Norihiro
Fang, Dingzhi
Tang, Wei
[J]. BIOLOGICAL & PHARMACEUTICAL BULLETIN, 2010, 33 (10) : 1728 - 1732

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