(2'R)-3',5'-di-O-acetyl-2'-fluorothymidine | 110483-41-5

• 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: (2'R)-3',5'-di-O-acetyl-2'-fluorothymidine
• 英文别名: [(2R,3R,4R,5R)-3-acetyloxy-4-fluoro-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl acetate
• CAS: 110483-41-5
• 化学式: C₁₄H₁₇FN₂O₇
• 分子量: 344.297
• InChiKey: RHPLWIMSYNDPPC-PRULPYPASA-N

物化性质

• 密度：
  1.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.42
• 重原子数：
  24.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  116.69
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  (2'R)-3',5'-di-O-acetyl-2'-fluorothymidine 在 1H-1,2,4-三唑 、 三乙胺 、 三氯氧磷 、 氨 作用下， 以 乙腈 、 1,4-二氧六环 、 甲醇 为溶剂， 以88.4 %的产率得到4-amino-1-[(2S,3R,4S,5S)-3-fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-5-methylpyrimidin-2-one
  参考文献：
  名称：

  [EN] PHOSPHORAMIDATES FOR THE TREATMENT OF HEPATITIS B VIRUS
  [FR] PHOSPHORAMIDATES POUR LE TRAITEMENT DU VIRUS DE L'HÉPATITE B

  摘要：

  Disclosed are compounds and compositions to the treatment of infectious diseases and methods of treating such diseases. The compounds and compositions include derivatives of clevudine. The compounds and compositions include derivatives of clevudine in combination with another antiviral agent. The compounds and compositions include derivatives of clevudine in combination with a phosphoramidate of lamivudine, adefovir, tenofovir, telbivudine, entecavir, or combinations thereof.

  公开号：

  WO2023044104A1
• 作为产物：
  描述：

  5-甲基尿甙 在 吡啶 、 碳酸二苯酯 、 碳酸氢钠 、 氟化氢吡啶 作用下， 以 1,4-二氧六环 、 六甲基磷酰三胺 为溶剂， 反应 18.5h， 生成 (2'R)-3',5'-di-O-acetyl-2'-fluorothymidine
  参考文献：
  名称：

  亚基因组HCV复制子系统中一系列d和1-2'-deoxy-2'-氟核糖核苷的合成及抗病毒活性。

  摘要：

  基于发现（2'R）-d-2'-deoxy-2'-氟胞苷作为有效的抗丙型肝炎病毒（HCV）剂，一系列d-和1-2'-deoxy-2'合成了具有5-和/或4-位修饰的-氟核糖核苷，并评估了其抗HCV和牛病毒性腹泻病毒（BVDV）的体外活性。合成中的关键步骤，即2'-氟基团的引入是通过用氟化氢-吡啶或氟化钾对2,2'-脱水核苷进行氟化，或用DAST对阿拉伯糖核苷进行氟化来实现的。在合成的27个类似物中，只有5-氟化合物，即（2'R）-d-2'-deoxy-2'，5-difluorocytidine（13），显示出有效的抗HCV活性和对核糖体RNA的毒性。用硫醇基取代4-氨基会导致活性降低，而4-甲硫基取代的类似物（25）会抑制核糖体RNA。由于N（4）-羟基胞嘧啶核苷（NHC）先前显示出有效的抗HCV活性，我们将N（4）-羟基和2'-氟的两个功能合并为一个分子，得到（2'R）-d -2'-脱氧-

  DOI：

  10.1016/j.bmc.2004.12.011

文献信息

• Growth Inhibition of <i>Mycobacterium </i><i>bovis</i>, <i>Mycobacterium </i><i>tuberculosis</i> and <i>Mycobacterium </i><i>avium</i> In Vitro:  Effect of 1-β-<scp>d</scp>-2‘-Arabinofuranosyl and 1-(2‘-Deoxy-2‘-fluoro-β-<scp>d</scp>-2‘-ribofuranosyl) Pyrimidine Nucleoside Analogs
  作者：Monika Johar、Tracey Manning、Christopher Tse、Nancy Desroches、B. Agrawal、Dennis Y. Kunimoto、Rakesh Kumar

  DOI：10.1021/jm0703901

  日期：2007.7.1

  The resurgence of tuberculosis and the emergence of multiple-drug-resistant strains of Mycobacteria necessitate the search for new classes of antimycobacterial agents. We synthesized a series of 1-beta-D-2'-arabinofuranosyl and 1-(2'-deoxy-2'-fluoro-beta-D-ribofuranosyl) pyrimidine nucleosides possessing diverse sets of alkynyl, alkenyl, alkyl, and halo substituents at the C-5 position of the uracil and investigated their effect on activity against M. tuberculosis, M. bovis, and M. avium. Among these molecules, 5-alkynyl-substituted derivatives emerged as potent inhibitors of M. bovis, M. tuberculosis, and M. avium. Nucleosides 1-beta-D-2'-arabinofuranosyl-5-dodecynyluracil (5), 1-(2'-deoxy-2'-fluoro-beta-D-ribofuranosyl)-5-dodecynyluracil (24), and 1-(2'-deoxy-2'-fluoro-beta-D-ribofuranosyl)-5-tetradecynyluracil (25) showed the highest antimycobacterial potency against M. bovis and M. tuberculosis. The MIC90 exhibited by compounds 5,24, and 25 was similar or close to that of the reference drug rifampicin. The most active compounds 5, 24, and 25 were also found to retain sensitivity against a rifampicin-resistant strain of M. tuberculosis H37Rv at similar concentrations. Some of these analogs also revealed in vitro antimicrobial effect against several other gram-positive pathogens.