5-(1-苯基-1,2,3-三唑-4-基)-2'-脱氧尿苷 | 1050649-04-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 中文名称: 5-(1-苯基-1,2,3-三唑-4-基)-2'-脱氧尿苷
• 英文名称: 5-(1-phenyl-1,2,3-triazol-4-yl)-2'-deoxyuridine
• 英文别名: 1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-(1-phenyltriazol-4-yl)pyrimidine-2,4-dione
• CAS: 1050649-04-1
• 化学式: C₁₇H₁₇N₅O₅
• 分子量: 371.352
• InChiKey: VKWYZHNGUBAUGJ-RRFJBIMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  130
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-(1-苯基-1,2,3-三唑-4-基)-2'-脱氧尿苷 在 吡啶 、 二异丙基铵盐四氮唑 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 18.0h， 生成 3'-O-(N,N-diisopropylamino-2-cyanoethoxyphosphinyl)-5-(1-phenyl-1H-1,2,3-triazol-4-yl)-2'-deoxyuridine
  参考文献：
  名称：

  Increasing the Stability of DNA:RNA Duplexes by Introducing Stacking Phenyl-Substituted Pyrazole, Furan, and Triazole Moieties in the Major Groove

  摘要：

  Consecutive incorporations of our previously published thymidine analogue, 5-(1-pheny1-1H-1,2,3-triazol-4-yl)-2'-deoxyuridine monomer W in oligonudeotides, has demonstrated significant duplex-stabilizing properties due to its efficient staking properties in the major groove of DNA:RNA duplexes. The corresponding 2'-deoxycytidine analogue is not as well-accommodated in duplexes, however, due to its clear preference for the ring-flipped coplanar conformation. In our present work, we have used oh initio calculations to design two new building blocks, 5-(5-phenylfuran-2-yl)-2'-deoxycytidine monomer Y and 5-(1-phenyl-1H-pyrazol-3-yl)-2'-deoxycytidine monomer Z, that emulate the conformation of W. These monomers were synthesized by Suzuki-Miyaura couplings, and the pyrazole moiety was obtained in a cycloaddition from N-phenylsydnone. We show that the novel analogues Y and Z engage in efficient stacking either with themselves or with W due to a better overlap of the aromatic moieties. Importantly, we demonstrate that this translates into very thermally stable DNA:RNA duplexes, thus making Y and especially Z good candidates for improving the binding affinities of oligonudeotide-based therapeutics. Since we now have both efficiently stacking T and C analogues in hand, any purine rich stretch can be effectively targeted using these simple analogues. Notably, we show that the introduction of the aromatic rings in the major groove does not significantly change the helical geometry.

  DOI：

  10.1021/acs.joc.5b01577
• 作为产物：
  描述：

  二乙酰基-2'脱氧尿苷 在 甲醇 、 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 ammonium cerium (IV) nitrate 、 四丁基氟化铵 、 氨 、 碘 、 copper(II) sulfate 、 sodium ascorbate 、 三乙胺 作用下， 以 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 1.0h， 生成 5-(1-苯基-1,2,3-三唑-4-基)-2'-脱氧尿苷
  参考文献：
  名称：

  Synthesis of new C5-(1-substituted-1,2,3-triazol-4 or 5-yl)-2′-deoxyuridines and their antiviral evaluation

  摘要：

  The synthesis and antiviral evaluation of a series of C5-(1,4- and 1,5-disubstituted-1,2,3-triazolo)-nucleoside derivatives is described. The key steps of this synthesis are regioselective Huisgen's 1,3-dipolar cycloaddition, using either copper-catalyzed azide-alkyne cycloaddition (CuAAC) or ruthenium-catalyzed azide-alkyne cycloaddition (RuAAC) under microwave activation. Some compounds among the 5a-1 series possess activity against herpes simplex viruses 1 and 2, varicella-zoster virus, human cytomegalovirus and vaccinia virus. Their cytostatic activities were determined against murine leukemia cells, human T-lymphocyte cells and cervix carcinoma cells. Compounds were also evaluated on a wide panel of RNA viruses, including Vesicular stomatitis virus, influenza viruses type A (HI NI and H3N2) and B in MDCK cell cultures, parainfluenza-3 virus, reovinis-1. Sindbis virus and Punta Toro virus in Vero cell cultures and Vesicular stomatitis, Coxsackie B4 and respiratory syncytial virus, with no specific antiviral effect. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.12.017

文献信息

• Efficient RNA-targeting by the introduction of aromatic stacking in the duplex major groove via 5-(1-phenyl-1,2,3-triazol-4-yl)-2′-deoxyuridines
  作者：Nicolai Krog Andersen、Navneet Chandak、Lucie Brulíková、Pawan Kumar、Michael Dalager Jensen、Frank Jensen、Pawan K. Sharma、Poul Nielsen

  DOI：10.1016/j.bmc.2010.05.019

  日期：2010.7

  Three pyrimidine nucleosides with differently substituted phenyltriazoles attached to the 5-position were prepared by Cu(I)-assisted azide-alkyne cycloadditions (CuAAC) and incorporated into oligonucleotides. Efficient pi-pi-stacking between two or more phenyltriazoles in the major groove was found to increase the thermal stability of a DNA: RNA duplex significantly. The best stacking, and most stable duplex, was obtained by a sulfonamide substituted derivative. (C) 2010 Elsevier Ltd. All rights reserved.
• Synthesis of new C5-(1-substituted-1,2,3-triazol-4 or 5-yl)-2′-deoxyuridines and their antiviral evaluation
  作者：Aurélien Montagu、Vincent Roy、Jan Balzarini、Robert Snoeck、Graciela Andrei、Luigi A. Agrofoglio

  DOI：10.1016/j.ejmech.2010.12.017

  日期：2011.2

  The synthesis and antiviral evaluation of a series of C5-(1,4- and 1,5-disubstituted-1,2,3-triazolo)-nucleoside derivatives is described. The key steps of this synthesis are regioselective Huisgen's 1,3-dipolar cycloaddition, using either copper-catalyzed azide-alkyne cycloaddition (CuAAC) or ruthenium-catalyzed azide-alkyne cycloaddition (RuAAC) under microwave activation. Some compounds among the 5a-1 series possess activity against herpes simplex viruses 1 and 2, varicella-zoster virus, human cytomegalovirus and vaccinia virus. Their cytostatic activities were determined against murine leukemia cells, human T-lymphocyte cells and cervix carcinoma cells. Compounds were also evaluated on a wide panel of RNA viruses, including Vesicular stomatitis virus, influenza viruses type A (HI NI and H3N2) and B in MDCK cell cultures, parainfluenza-3 virus, reovinis-1. Sindbis virus and Punta Toro virus in Vero cell cultures and Vesicular stomatitis, Coxsackie B4 and respiratory syncytial virus, with no specific antiviral effect. (C) 2010 Elsevier Masson SAS. All rights reserved.
• Increasing the Stability of DNA:RNA Duplexes by Introducing Stacking Phenyl-Substituted Pyrazole, Furan, and Triazole Moieties in the Major Groove
  作者：Mick Hornum、Pawan Kumar、Patricia Podsiadly、Poul Nielsen

  DOI：10.1021/acs.joc.5b01577

  日期：2015.10.2

  Consecutive incorporations of our previously published thymidine analogue, 5-(1-pheny1-1H-1,2,3-triazol-4-yl)-2'-deoxyuridine monomer W in oligonudeotides, has demonstrated significant duplex-stabilizing properties due to its efficient staking properties in the major groove of DNA:RNA duplexes. The corresponding 2'-deoxycytidine analogue is not as well-accommodated in duplexes, however, due to its clear preference for the ring-flipped coplanar conformation. In our present work, we have used oh initio calculations to design two new building blocks, 5-(5-phenylfuran-2-yl)-2'-deoxycytidine monomer Y and 5-(1-phenyl-1H-pyrazol-3-yl)-2'-deoxycytidine monomer Z, that emulate the conformation of W. These monomers were synthesized by Suzuki-Miyaura couplings, and the pyrazole moiety was obtained in a cycloaddition from N-phenylsydnone. We show that the novel analogues Y and Z engage in efficient stacking either with themselves or with W due to a better overlap of the aromatic moieties. Importantly, we demonstrate that this translates into very thermally stable DNA:RNA duplexes, thus making Y and especially Z good candidates for improving the binding affinities of oligonudeotide-based therapeutics. Since we now have both efficiently stacking T and C analogues in hand, any purine rich stretch can be effectively targeted using these simple analogues. Notably, we show that the introduction of the aromatic rings in the major groove does not significantly change the helical geometry.