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新型含 1,2,3-三唑连接基团的异噁唑烷核苷酸类似物的设计、合成、抗病毒和细胞毒性评价。

Design, synthesis, antiviral and cytostatic evaluation of novel isoxazolidine nucleotide analogues with a 1,2,3-triazole linker.

机构信息

Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Łódź, 90-151 Łódź, Muszyńskiego 1, Poland.

出版信息

Eur J Med Chem. 2012 Jan;47(1):501-9. doi: 10.1016/j.ejmech.2011.11.021. Epub 2011 Nov 20.

DOI:10.1016/j.ejmech.2011.11.021
PMID:22137458
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7125624/
Abstract

Azidation (TMSN(3), SnCl(4)) of a 9:1 mixture of trans- and cis-5-acetoxy-2-methylisoxazolidin-3-yl-3-phosphonates at the anomeric carbon atom led to the formation of the equimolar mixture of cis- and trans-5-azido-2-methylisoxazolidin-3-yl-3-phosphonates, which were efficiently separated. The 1,3-dipolar cycloaddition of pure trans- and cis-5-azidoisoxazolidin-3-yl-3-phosphonates with selected alkynes gave the respective nucleoside mimetics containing a 1,2,3-triazole linker. The (1,2,3-triazolyl)isoxazolidine phosphonates obtained herein were evaluated in vitro for activity against a variety of DNA and RNA viruses. None of the compounds were endowed with antiviral activity at subtoxic concentrations. Compounds 15f-j and 16f-j were cytostatic in the higher micromolar range.

摘要

将 9:1 的反式和顺式 5-乙酰氧基-2-甲基异噁唑烷-3-基-3-膦酸酯混合物在糖苷碳原子处进行叠氮化（TMSN(3)，SnCl(4)），导致顺式和反式 5-叠氮-2-甲基异噁唑烷-3-基-3-膦酸酯以等摩尔混合物形成，可有效分离。纯反式和顺式 5-叠氮异噁唑烷-3-基-3-膦酸酯与选定的炔烃的 1,3-偶极环加成反应分别得到含有 1,2,3-三唑键的核苷类似物。本文获得的（1,2,3-三唑基）异噁唑烷膦酸酯在体外对多种 DNA 和 RNA 病毒的活性进行了评估。在亚毒性浓度下，没有一种化合物具有抗病毒活性。化合物 15f-j 和 16f-j 在较高的微摩尔范围内具有细胞毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/230d/7125624/a7b03da06637/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/230d/7125624/b721641b75d8/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/230d/7125624/d02720c958cf/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/230d/7125624/a341368bcc5b/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/230d/7125624/9c4e9a5e65ff/sc1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/230d/7125624/bbaed58ceef9/sc2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/230d/7125624/75e8d3d9254b/sc3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/230d/7125624/9731798f15d2/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/230d/7125624/16dbd1d3dcd7/sc4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/230d/7125624/a7b03da06637/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/230d/7125624/b721641b75d8/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/230d/7125624/d02720c958cf/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/230d/7125624/a341368bcc5b/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/230d/7125624/9c4e9a5e65ff/sc1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/230d/7125624/bbaed58ceef9/sc2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/230d/7125624/75e8d3d9254b/sc3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/230d/7125624/9731798f15d2/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/230d/7125624/16dbd1d3dcd7/sc4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/230d/7125624/a7b03da06637/gr4.jpg

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2
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Bioorg Med Chem Lett. 2010 Oct 1;20(19):5831-4. doi: 10.1016/j.bmcl.2010.07.126. Epub 2010 Aug 3.
3
Synthesis and biological activity of glycosyl-1H-1,2,3-triazoles.
非对映选择性合成阻转异构的吡唑基吡咯并[3,4-]异恶唑烷：吡唑基硝酮与面式不同的马来酰亚胺的环加成反应：深入的核磁共振和密度泛函理论研究
RSC Adv. 2020 Jan 6;10(2):845-850. doi: 10.1039/c9ra10039c. eCollection 2020 Jan 2.
4
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Tetrahedron. 2016 Dec 15;72(50):8294-8308. doi: 10.1016/j.tet.2016.10.073. Epub 2016 Nov 2.
5
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5
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Carbohydr Res. 2010 Jun 16;345(9):1123-34. doi: 10.1016/j.carres.2010.03.041. Epub 2010 Apr 4.
6
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J Med Chem. 2008 Oct 23;51(20):6263-70. doi: 10.1021/jm800149m. Epub 2008 Sep 30.