• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

改善核碱基类似物T-705/T-1105作为潜在抗病毒药物的性能。

Improving properties of the nucleobase analogs T-705/T-1105 as potential antiviral.

作者信息

Jia Xiao, Ganter Benedikt, Meier Chris

机构信息

Organic Chemistry, Department of Chemistry, Faculty of Mathematics, Informatics and Natural Sciences, Universität Hamburg, Hamburg, Germany.

出版信息

Annu Rep Med Chem. 2021;57:1-47. doi: 10.1016/bs.armc.2021.08.002. Epub 2021 Oct 28.

DOI:10.1016/bs.armc.2021.08.002
PMID:34728864
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8553380/
Abstract

In this minireview we describe our work on the improvement of the nucleobase analogs Favipiravir (T-705) und its non-fluorinated derivative T-1105 as influenza and SARS-CoV-2 active compounds. Both nucleobases were converted into nucleotides and then included in our nucleotide prodrugs technologies cycloSal-monophosphates, Diro-nucleoside diphosphates and Triro-nucleoside triphosphates. Particularly the Diro-derivatives of T-1105-RDP proved to be very active against influenza viruses. T-1105-derivatives in general were found to be more antivirally active as compared to their T-705 counterpart. This may be due to the low chemical stability of all ribosylated derivatives of T-705. The ribosyltriphosphate derivative of T-1105 was studied for the potential to act as a inhibitor of the SARS-CoV-2 RdRp and was found to be an extremely potent compound causing lethal mutagenesis. The pronucleotide technologies, the chemical synthesis, the biophysical properties and the biological effects of the compounds will be addressed as well.

摘要

在本综述中，我们描述了我们在改进核碱基类似物法匹拉韦（T-705）及其非氟化衍生物T-1105方面的工作，它们作为流感和SARS-CoV-2活性化合物。这两种核碱基都被转化为核苷酸，然后被纳入我们的核苷酸前药技术环化单磷酸酯、二核苷二磷酸酯和三核苷三磷酸酯中。特别是T-1105-RDP的二核苷衍生物对流感病毒表现出非常高的活性。总体而言，发现T-1105衍生物比其对应的T-705衍生物具有更高的抗病毒活性。这可能是由于T-705的所有核糖基化衍生物的化学稳定性较低。对T-1105的核糖基三磷酸酯衍生物作为SARS-CoV-2 RdRp抑制剂的潜力进行了研究，发现它是一种极其有效的化合物，可导致致死性诱变。还将讨论这些化合物的前核苷酸技术、化学合成、生物物理性质和生物学效应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/635e673e08f6/sch01-17-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/bb73d2a90e2b/f01-01-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/9e022e9b4596/f01-02-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/ec1a14f617fa/sch01-01-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/883ac1582aeb/sch01-02-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/7f36e9c38847/sch01-03-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/7feada20db6b/sch01-04-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/c654ad8417ed/sch01-05-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/2c217fe5b955/f01-03-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/b13e9395b956/sch01-06-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/d88768309b52/sch01-07-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/add52f07baec/sch01-08-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/efe18b8f0a6a/sch01-09-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/bc93ed610182/sch01-10-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/6c8c4d534578/f01-04-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/4785dbd1d41d/f01-05-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/d4403e9950ad/sch01-11-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/1491ce5c5e5d/sch01-12-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/506ea798b679/sch01-13-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/b65a91359ee0/sch01-14-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/a08929b1cfd2/sch01-15-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/d8a7588a0aa8/sch01-16-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/635e673e08f6/sch01-17-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/bb73d2a90e2b/f01-01-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/9e022e9b4596/f01-02-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/ec1a14f617fa/sch01-01-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/883ac1582aeb/sch01-02-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/7f36e9c38847/sch01-03-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/7feada20db6b/sch01-04-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/c654ad8417ed/sch01-05-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/2c217fe5b955/f01-03-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/b13e9395b956/sch01-06-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/d88768309b52/sch01-07-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/add52f07baec/sch01-08-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/efe18b8f0a6a/sch01-09-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/bc93ed610182/sch01-10-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/6c8c4d534578/f01-04-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/4785dbd1d41d/f01-05-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/d4403e9950ad/sch01-11-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/1491ce5c5e5d/sch01-12-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/506ea798b679/sch01-13-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/b65a91359ee0/sch01-14-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/a08929b1cfd2/sch01-15-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/d8a7588a0aa8/sch01-16-9780323915113_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0620/8553380/635e673e08f6/sch01-17-9780323915113_lrg.jpg

相似文献

1
Improving properties of the nucleobase analogs T-705/T-1105 as potential antiviral.改善核碱基类似物T-705/T-1105作为潜在抗病毒药物的性能。
Annu Rep Med Chem. 2021;57:1-47. doi: 10.1016/bs.armc.2021.08.002. Epub 2021 Oct 28.
2
Bis(benzoyloxybenzyl)-DiPPro nucleoside diphosphates of anti-HIV active nucleoside analogues.抗HIV活性核苷类似物的双（苯甲酰氧基苄基）-二异丙酯核苷二磷酸。
ChemMedChem. 2015 May;10(5):891-900. doi: 10.1002/cmdc.201500063. Epub 2015 Apr 2.
3
Lipophilic Nucleoside Triphosphate Prodrugs of Anti-HIV Active Nucleoside Analogs as Potential Antiviral Compounds.亲脂性核苷三磷酸前药的抗 HIV 活性核苷类似物作为潜在的抗病毒化合物。
Adv Sci (Weinh). 2023 Dec;10(36):e2306021. doi: 10.1002/advs.202306021. Epub 2023 Oct 26.
4
Cyclosal-pronucleotides--development of first and second generation chemical trojan horses for antiviral chemotherapy.环孢素原核苷酸——用于抗病毒化疗的第一代和第二代化学特洛伊木马的研发。
Front Biosci. 2004 Jan 1;9:873-90. doi: 10.2741/1283.
5
Application of the cycloSal-prodrug approach for improving the biological potential of phosphorylated biomolecules.环水杨酸前药方法在提高磷酸化生物分子生物学潜力方面的应用。
Antiviral Res. 2006 Sep;71(2-3):282-92. doi: 10.1016/j.antiviral.2006.04.011. Epub 2006 May 9.
6
The DiPPro approach: synthesis, hydrolysis, and antiviral activity of lipophilic d4T diphosphate prodrugs.DiPPro 方法：亲脂性 d4T 二磷酸前药的合成、水解和抗病毒活性。
ChemMedChem. 2014 Apr;9(4):762-75. doi: 10.1002/cmdc.201300500. Epub 2014 Mar 11.
7
γ-Non-Symmetrically Dimasked TriPPPro Prodrugs as Potential Antiviral Agents against HIV.γ-非对称掩蔽三嗪基丙基前药作为抗 HIV 的潜在抗病毒药物。
ChemMedChem. 2021 Feb 4;16(3):499-512. doi: 10.1002/cmdc.202000712. Epub 2020 Nov 17.
8
Antiviral nucleoside analogs.抗病毒核苷类似物。
Chem Heterocycl Compd (N Y). 2021;57(4):326-341. doi: 10.1007/s10593-021-02912-8. Epub 2021 May 14.
9
Enhancing the Antiviral Potency of Nucleobases for Potential Broad-Spectrum Antiviral Therapies.增强核苷的抗病毒效力，用于潜在的广谱抗病毒疗法。
Viruses. 2021 Dec 14;13(12):2508. doi: 10.3390/v13122508.
10
Rational Development of Nucleoside Diphosphate Prodrugs: DiPPro-Compounds.核苷二磷酸前药的合理开发：DiPPro化合物
Curr Med Chem. 2015;22(34):3933-50. doi: 10.2174/0929867322666150825163119.

引用本文的文献

1
Green synthesis of structural analogs of favipiravir.法匹拉韦结构类似物的绿色合成。
RSC Adv. 2025 May 27;15(22):17570-17579. doi: 10.1039/d5ra02613j. eCollection 2025 May 21.
2
Novel Anti-Enterovirus A71 Compounds Discovered by Repositioning Antivirals from the Open-Source MMV Pandemic Response Box.通过重新利用开源MMV大流行应对药盒中的抗病毒药物发现新型抗肠道病毒A71化合物
Pharmaceuticals (Basel). 2024 Jun 14;17(6):785. doi: 10.3390/ph17060785.
3
Antiviral Activity of Lipophilic Nucleoside Tetraphosphate Compounds.疏水性核苷四磷酸化合物的抗病毒活性。

本文引用的文献

1
Simeprevir Potently Suppresses SARS-CoV-2 Replication and Synergizes with Remdesivir.西米普韦能有效抑制新型冠状病毒复制，并与瑞德西韦协同作用。
ACS Cent Sci. 2021 May 26;7(5):792-802. doi: 10.1021/acscentsci.0c01186. Epub 2021 Apr 15.
2
γ-Non-Symmetrically Dimasked TriPPPro Prodrugs as Potential Antiviral Agents against HIV.γ-非对称掩蔽三嗪基丙基前药作为抗 HIV 的潜在抗病毒药物。
ChemMedChem. 2021 Feb 4;16(3):499-512. doi: 10.1002/cmdc.202000712. Epub 2020 Nov 17.
3
Favipiravir at high doses has potent antiviral activity in SARS-CoV-2-infected hamsters, whereas hydroxychloroquine lacks activity.
J Med Chem. 2024 Feb 22;67(4):2864-2883. doi: 10.1021/acs.jmedchem.3c02022. Epub 2024 Feb 12.
4
Lipophilic Nucleoside Triphosphate Prodrugs of Anti-HIV Active Nucleoside Analogs as Potential Antiviral Compounds.亲脂性核苷三磷酸前药的抗 HIV 活性核苷类似物作为潜在的抗病毒化合物。
Adv Sci (Weinh). 2023 Dec;10(36):e2306021. doi: 10.1002/advs.202306021. Epub 2023 Oct 26.
5
Tracing down the Updates on Dengue Virus-Molecular Biology, Antivirals, and Vaccine Strategies.探寻登革病毒的最新研究进展——分子生物学、抗病毒药物及疫苗策略
Vaccines (Basel). 2023 Aug 5;11(8):1328. doi: 10.3390/vaccines11081328.
6
6-Thioguanosine Monophosphate Prodrugs Display Enhanced Performance against Thiopurine-Resistant Leukemia and Breast Cancer Cells.6-硫代鸟苷单磷酸前药对巯基嘌呤耐药白血病和乳腺癌细胞显示出增强的疗效。
J Med Chem. 2022 Nov 24;65(22):15165-15173. doi: 10.1021/acs.jmedchem.2c01010. Epub 2022 Nov 14.
7
Within and Beyond the Nucleotide Addition Cycle of Viral RNA-dependent RNA Polymerases.病毒RNA依赖的RNA聚合酶的核苷酸添加循环之内及之外
Front Mol Biosci. 2022 Jan 10;8:822218. doi: 10.3389/fmolb.2021.822218. eCollection 2021.
高剂量的法匹拉韦对感染 SARS-CoV-2 的仓鼠具有强大的抗病毒活性，而羟氯喹则没有活性。
Proc Natl Acad Sci U S A. 2020 Oct 27;117(43):26955-26965. doi: 10.1073/pnas.2014441117. Epub 2020 Oct 9.
4
Rapid incorporation of Favipiravir by the fast and permissive viral RNA polymerase complex results in SARS-CoV-2 lethal mutagenesis.快速且允许的病毒 RNA 聚合酶复合物使法匹拉韦迅速掺入，导致 SARS-CoV-2 致命突变。
Nat Commun. 2020 Sep 17;11(1):4682. doi: 10.1038/s41467-020-18463-z.
5
The Enzymatic Activity of the nsp14 Exoribonuclease Is Critical for Replication of MERS-CoV and SARS-CoV-2.nsp14 外切核酸酶的酶活性对于 MERS-CoV 和 SARS-CoV-2 的复制至关重要。
J Virol. 2020 Nov 9;94(23). doi: 10.1128/JVI.01246-20.
6
Coronavirus RNA Proofreading: Molecular Basis and Therapeutic Targeting.冠状病毒RNA校对：分子基础与治疗靶点
Mol Cell. 2020 Sep 3;79(5):710-727. doi: 10.1016/j.molcel.2020.07.027. Epub 2020 Aug 4.
7
Effect of favipiravir and an anti-inflammatory strategy for COVID-19.法匹拉韦及抗炎策略对新型冠状病毒肺炎的影响
Crit Care. 2020 Jul 9;24(1):413. doi: 10.1186/s13054-020-03137-5.
8
Lipophilic Triphosphate Prodrugs of Various Nucleoside Analogues.各种核苷类似物的亲脂性三磷酸前药。
J Med Chem. 2020 Jul 9;63(13):6991-7007. doi: 10.1021/acs.jmedchem.0c00358. Epub 2020 Jun 29.
9
Anti-HIV-Active Nucleoside Triphosphate Prodrugs.抗 HIV 活性核苷三磷酸前药。
J Med Chem. 2020 Jun 11;63(11):6003-6027. doi: 10.1021/acs.jmedchem.0c00271. Epub 2020 Jun 3.
10
An Update on Current Therapeutic Drugs Treating COVID-19.治疗新型冠状病毒肺炎的当前治疗药物最新情况
Curr Pharmacol Rep. 2020;6(3):56-70. doi: 10.1007/s40495-020-00216-7. Epub 2020 May 11.