5-dodecyloxymethyl-2'-deoxyuridine | 496042-45-6

• 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-dodecyloxymethyl-2'-deoxyuridine
• 英文别名: 5-(dodecoxymethyl)-4-hydroxy-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]pyrimidin-2-one；5-(dodecoxymethyl)-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione
• CAS: 496042-45-6
• 化学式: C₂₂H₃₈N₂O₆
• 分子量: 426.554
• InChiKey: YSDPBQKPLINJOX-XUVXKRRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  30
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-dodecyloxymethyl-2'-deoxyuridine 在 咪唑 、 sodium azide 、 DL-dithiothreitol 、 氨 、 水 、 碘 、 三苯基膦 作用下， 以 1,4-二氧六环 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 5-dodecyloxymethyl-5'-amino-2',5'-dideoxyuridine
  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
• 作为产物：
  描述：

  3',5'-di-O-acetyl-5-bromomethyl-2'-deoxyuridine 在 氨 、 水 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 69.0h， 生成 5-dodecyloxymethyl-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 evaluation of C-5 modified 2′-deoxyuridine monophosphates as inhibitors of M. tuberculosis thymidylate synthase
  作者：Liudmila A. Alexandrova、Vladimir O. Chekhov、Eduard R. Shmalenyuk、Sergey N. Kochetkov、Rania Abu El-Asrar、Piet Herdewijn

  DOI：10.1016/j.bmc.2015.09.053

  日期：2015.11

  5'-monophosphates of 5-substituted 2'-deoxyuridine analogs, which recently demonstrated in vitro substantial suppression of two strains of Mycobacterium tuberculosis growth (virulent laboratory H37Rv and multiple resistant MS-115), has been synthesized and evaluated as potential inhibitors of M. tuberculosis thymidylate synthases: classical (ThyA) and flavin dependent thymidylate synthase (ThyX). A systematic SAR

  已经合成了一系列5个取代的2'-脱氧尿苷类似物的5'-单磷酸酯，它们最近在体外显示出对两种结核分枝杆菌生长菌株（毒力实验室H37Rv和多重耐药性MS-115）具有实质性抑制作用，并被评估为潜在的结核分枝杆菌胸苷酸合酶的抑制剂：经典（ThyA）和黄素依赖性胸苷酸合酶（ThyX）。一项系统的SAR研究和对接揭示了5-十一烷氧基甲基-2'-脱氧尿苷5'-单磷酸酯3b，相对于ThyX的IC50值为8.32μM。所有衍生物均缺乏针对ThyA的活性。可以假设3b的作用机制可能部分与ThyX的抑制有关。
• Oligoglycol carbonate prodrugs of 5-modified 2'-deoxyuridines: synthesis and antibacterial activity
  作者：Sergey D. Negrya、Maxim V. Jasko、Dmitriy A. Makarov、Inna L. Karpenko、Pavel N. Solyev、Vladimir O. Chekhov、Olga V. Efremenkova、Byasilya F. Vasilieva、Tatiana A. Efimenko、Sergey N. Kochetkov、Liudmila A. Alexandrova

  DOI：10.1016/j.mencom.2022.07.002

  日期：2022.7
• 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.