5-[(4-decyl)-1,2,3-triazol-1-yl]methyl-2′-deoxyuridine | 1450644-60-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 5-[(4-decyl)-1,2,3-triazol-1-yl]methyl-2′-deoxyuridine
• 英文别名: 5-[4-(1-decyl)-1,2,3-triazol-1-yl]methyl-2′-deoxyuridine；5-[(4-decyl-1,2,3-triazol-1-yl)methyl]-2'-deoxyuridine；5-[(4-decyltriazol-1-yl)methyl]-4-hydroxy-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]pyrimidin-2-one；5-[(4-decyltriazol-1-yl)methyl]-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione
• CAS: 1450644-60-6
• 化学式: C₂₂H₃₅N₅O₅
• 分子量: 449.55
• InChiKey: SKNZUOHKAQCCAV-XUVXKRRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  32
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 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-[(4-decyl)-1,2,3-triazol-1-yl]methyl-2′-deoxyuridine 在 吡啶 、 咪唑 、 溶剂黄146 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 60.0h， 生成 3'-O-(tert-butyl)dimethylsilyl-5'-O-carbonyltetraethylene glycol-5-[(4-decyl-1,2,3-triazol-1-yl)methyl]-2'-deoxyuridine
  参考文献：
  名称：

  5-修饰的2'-脱氧尿苷的水溶性前药的合成及其抗菌活性。

  摘要：

  最近，我们合成了一组嘧啶核苷衍生物，它们在核酸碱基的5位带有扩展的烷基三唑基甲基取代基，并显示出它们对结核分枝杆菌有毒力的实验室菌株H37Rv和抗药性MS-115菌株的显着活性。较长的疏水取代基的存在导致核苷水溶性降低，从而使其抗菌活性难以研究。合成了一系列水溶性的5-修饰的2'-脱氧尿苷4a-c和8a-c。与母体化合物1a和1b相比，它们的溶解度至少高出两个数量级。它们的半水解时间为5-12小时，对于临床前药而言，这被认为是最佳的。

  DOI：

  10.1038/s41429-019-0273-x
• 作为产物：
  描述：

  3',5'-di-O-acetyl-5-bromomethyl-2'-deoxyuridine 在 sodium azide 、 copper(ll) sulfate pentahydrate 、 氨 、 水 、 sodium ascorbate 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 38.0h， 生成 5-[(4-decyl)-1,2,3-triazol-1-yl]methyl-2′-deoxyuridine
  参考文献：
  名称：

  Inhibition of Mycobacterium tuberculosis strains H37Rv and MDR MS-115 by a new set of C5 modified pyrimidine nucleosides

  摘要：

  Two sets of pyrimidine nucleoside derivatives bearing extended alkyloxymethyl or alkyltriazolidomethyl substituents at position 5 of the nucleobase were synthesized and evaluated as potential antituberculosis agents. The impact of modifications at 3'- and 5'-positions of the carbohydrate moiety on the antimycobacterial activity and cytotoxicity was studied. The highest effect was shown for 5-dodecyloxymethyl-2'-deoxyuridine, 5-decyltriazolidomethyl-2'-deoxyuridine, and 5-dodecyltriazolidomethyl-2'-deoxycytidine. They effectively inhibited the growth of two Mycobacterium tuberculosis strains in vitro, laboratory H37Rv (MIC99 = 20, 10, and 20 mu g/mL, respectively) and clinical MDR MS-115 resistant to five top antituberculosis drugs (MIC99 = 50, 10, and 10 mu g/mL, respectively). (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.07.003

文献信息

• Synthesis and antimicrobial properties of 5,5′-modified 2′,5′-dideoxyuridines
  作者：Sergey D. Negria、Inna L. Karpenko、Olga V. Efremenkova、Alexander O. Chizhov、Sergey N. Kochetkov、Liudmila A. Alexandrova

  DOI：10.1515/hc-2015-0166

  日期：2015.10.1

  Abstract An effective method of synthesis of 5,5′-modified 2′,5′-dideoxyuridine derivatives is based on sequential 5′-iodination and azidation of 5-[4-(1-decyl)-1,2,3-triazol-1-yl]methyl-2′-deoxyuridine followed by 1,3-dipolar cycloaddition of the intermediate azide with an olefin under the catalysis of Cu(I) resulting in 75–85% yield of 5′-[4-substituted (1,2,3-triazol-1-yl]-5-[4-(1-decyl)-1,2,3-

  摘要 一种合成 5,5'-修饰的 2',5'-双脱氧尿苷衍生物的有效方法是基于 5-[4-(1-癸基)-1,2,3-三唑的顺序 5'-碘化和叠氮化。 -1-基]甲基-2'-脱氧尿苷，然后在Cu（I）的催化下，中间体叠氮化物与烯烃进行1,3-偶极环加成，得到75-85%的5'-[4-取代（ 1,2,3-triazol-1-yl]-5-[4-(1-decyl)-1,2,3-triazol-1-yl]methyl-2',5'-dideoxyuridine. 化合物如下在 Vero、A549 细胞和 Jurkat 细胞培养物中具有低细胞毒性，并且没有表现出明显的抗菌活性。
• Synthesis of water-soluble prodrugs of 5-modified 2ʹ-deoxyuridines and their antibacterial activity
  作者：Sergey D. Negrya、Maxim V. Jasko、Pavel N. Solyev、Inna L. Karpenko、Olga V. Efremenkova、Byazilya F. Vasilyeva、Irina G. Sumarukova、Sergey N. Kochetkov、Liudmila A. Alexandrova

  DOI：10.1038/s41429-019-0273-x

  日期：2020.4

  set of pyrimidine nucleoside derivatives bearing extended alkyltriazolylmethyl substituents at position 5 of the nucleic base, and showed their significant activity against Mycobacterium tuberculosis virulent laboratory strain H37Rv as well as drug-resistant MS-115 strain. The presence of a lengthy hydrophobic substituent leads to the reduction of nucleoside water solubility making their antibacterial

  最近，我们合成了一组嘧啶核苷衍生物，它们在核酸碱基的5位带有扩展的烷基三唑基甲基取代基，并显示出它们对结核分枝杆菌有毒力的实验室菌株H37Rv和抗药性MS-115菌株的显着活性。较长的疏水取代基的存在导致核苷水溶性降低，从而使其抗菌活性难以研究。合成了一系列水溶性的5-修饰的2'-脱氧尿苷4a-c和8a-c。与母体化合物1a和1b相比，它们的溶解度至少高出两个数量级。它们的半水解时间为5-12小时，对于临床前药而言，这被认为是最佳的。
• Inhibition of Mycobacterium tuberculosis strains H37Rv and MDR MS-115 by a new set of C5 modified pyrimidine nucleosides
  作者：Eduard R. Shmalenyuk、Larisa N. Chernousova、Inna L. Karpenko、Sergey N. Kochetkov、Tatiana G. Smirnova、Sofia N. Andreevskaya、Alexander O. Chizhov、Olga V. Efremenkova、Ludmila A. Alexandrova

  DOI：10.1016/j.bmc.2013.07.003

  日期：2013.9

  Two sets of pyrimidine nucleoside derivatives bearing extended alkyloxymethyl or alkyltriazolidomethyl substituents at position 5 of the nucleobase were synthesized and evaluated as potential antituberculosis agents. The impact of modifications at 3'- and 5'-positions of the carbohydrate moiety on the antimycobacterial activity and cytotoxicity was studied. The highest effect was shown for 5-dodecyloxymethyl-2'-deoxyuridine, 5-decyltriazolidomethyl-2'-deoxyuridine, and 5-dodecyltriazolidomethyl-2'-deoxycytidine. They effectively inhibited the growth of two Mycobacterium tuberculosis strains in vitro, laboratory H37Rv (MIC99 = 20, 10, and 20 mu g/mL, respectively) and clinical MDR MS-115 resistant to five top antituberculosis drugs (MIC99 = 50, 10, and 10 mu g/mL, respectively). (C) 2013 Elsevier Ltd. All rights reserved.