1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-4-thio-5-ethyluracil | 95740-20-8

• 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: 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-4-thio-5-ethyluracil
• 英文别名: 5-ethyl-1-[(2R,3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-sulfanylidenepyrimidin-2-one
• CAS: 95740-20-8
• 化学式: C₁₁H₁₅FN₂O₄S
• 分子量: 290.316
• InChiKey: DYWDEMMDRVBYTR-IBCQBUCCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-4-thio-5-ethyluracil 在 氨 作用下， 以 甲醇 、 水 为溶剂， 反应 29.0h， 生成 4-氨基-1-(2-脱氧-2-氟-beta-D-阿拉伯糖呋喃基)-5-乙基-2(1H)-嘧啶酮
  参考文献：
  名称：

  核苷。133. 5-烯基-1-（2-脱氧-2-氟-β-D-阿拉伯呋喃糖基）胞嘧啶核苷和相关嘧啶核苷的合成作为潜在的抗病毒剂。

  摘要：

  由相应的5-碘（FIAC，1）和/或5-氯汞，完成在C-5上具有卤乙烯基或乙烯基取代基的1-（2-脱氧-2-氟-β-D-阿拉伯呋喃糖基）胞嘧啶的合成Li2PdCl4-和Pd（OAc）2介导的偶联反应的核苷类似物。对5-乙基尿嘧啶核苷3的苯甲酰化衍生物进行硫代化，然后进行S-甲基化，然后进行氨解，得到了5-乙基-2'-氟-ara-C。5-乙炔基-2'-氟代-ara-C（19a）和5-乙炔基-2'-氟代-ara-U（19b）也分别通过PdII / CuI与（三甲基甲硅烷基）乙炔催化偶联。通过使用H 2 O / Me 2 SO对初始偶联产物进行选择性糖脱保护，可以分离出相应的5- [2-（三甲基甲硅烷基）乙炔基]衍生物18a和18b。大多数新化合物在体外均表现出针对HSV-1和HSV-2的活性，已知的相应的较早合成的5-链烯基尿嘧啶核苷也是如此。5-乙烯基胞嘧啶核苷10和尿嘧啶核苷分别对HSV-1（ED90分别为0

  DOI：

  10.1021/jm00383a009
• 作为产物：
  描述：

  1-(3',5'-di-O-benzoyl-2'-deoxy-2'-fluoro-β-D-arabinofuranofuranosyl)-5-ethyluracil 在 tetraphosphorus decasulfide 、 sodium methylate 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 4.25h， 生成 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-4-thio-5-ethyluracil
  参考文献：
  名称：

  核苷。133. 5-烯基-1-（2-脱氧-2-氟-β-D-阿拉伯呋喃糖基）胞嘧啶核苷和相关嘧啶核苷的合成作为潜在的抗病毒剂。

  摘要：

  由相应的5-碘（FIAC，1）和/或5-氯汞，完成在C-5上具有卤乙烯基或乙烯基取代基的1-（2-脱氧-2-氟-β-D-阿拉伯呋喃糖基）胞嘧啶的合成Li2PdCl4-和Pd（OAc）2介导的偶联反应的核苷类似物。对5-乙基尿嘧啶核苷3的苯甲酰化衍生物进行硫代化，然后进行S-甲基化，然后进行氨解，得到了5-乙基-2'-氟-ara-C。5-乙炔基-2'-氟代-ara-C（19a）和5-乙炔基-2'-氟代-ara-U（19b）也分别通过PdII / CuI与（三甲基甲硅烷基）乙炔催化偶联。通过使用H 2 O / Me 2 SO对初始偶联产物进行选择性糖脱保护，可以分离出相应的5- [2-（三甲基甲硅烷基）乙炔基]衍生物18a和18b。大多数新化合物在体外均表现出针对HSV-1和HSV-2的活性，已知的相应的较早合成的5-链烯基尿嘧啶核苷也是如此。5-乙烯基胞嘧啶核苷10和尿嘧啶核苷分别对HSV-1（ED90分别为0

  DOI：

  10.1021/jm00383a009

文献信息

• Discovery of novel 5-(ethyl or hydroxymethyl) analogs of 2′-‘up’ fluoro (or hydroxyl) pyrimidine nucleosides as a new class of Mycobacterium tuberculosis, Mycobacterium bovis and Mycobacterium avium inhibitors
  作者：Neeraj Shakya、Naveen C. Srivastav、Sudha Bhavanam、Chris Tse、Nancy Desroches、Babita Agrawal、Dennis Y. Kunimoto、Rakesh Kumar

  DOI：10.1016/j.bmc.2012.05.004

  日期：2012.7

  Discovery of novel antimycobacterial compounds that work on distinctive targets and by diverse mechanisms of action is urgently required for the treatment of mycobacterial infections due to the emerging global health threat of tuberculosis. We have identified a new class of 5-ethyl or hydroxy (or methoxy) methyl-substituted pyrimidine nucleosides as potent inhibitors of Mycobacterium bovis, Mycobacterium tuberculosis (H37Ra, H37Rv) and Mycobacterium avium. A series of 2'-'up' fluoro (or hydroxy) nucleosides (1, 2,4-6, 9, 10, 13, 16, 18, 21, 24) was synthesized and evaluated for antimycobacterial activity. Among 20-fluorinated compounds, 1-(3-bromo-2,3-dideoxy-2-fluoro-beta-D-arabinofuranosyl)-5-ethyluracil (13) exhibited promising activity against M. bovis and Mtb alone, and showed synergism when combined with isoniazid. The most active compound emerging from these studies, 1-(beta-D-arabinofuranosyl)-4-thio-5hydroxymethyluracil (21) inhibited Mtb (H37Ra) (MIC50 = 0.5 mu g/mL) and M. bovis (MIC50 = 0.5 mu g/mL) at low concentrations, and was ten times more potent against Mtb (H37Ra) than cycloserine (MIC50 = 5.0 mu g/mL), a second line drug. It also showed an additive effect when combined with isoniazid. Compound 21 retained sensitivity against a rifampicin-resistant (H37Rv) strain of Mtb (MIC50 = 1 mu g/mL) at concentrations similar to that for a rifampicin-sensitive (H37Rv) strain, suggesting that it has no cross-resistance to a first-line anti-TB drug. In addition, the replication of M. avium was also inhibited by 21 (MIC50 = 10 mu g/mL). No cellular toxicity of 13 or 21 was observed up to the highest concentration tested (CC50 > 100 mu g/mL). These observations offer promise for a new drug treatment regimen to augment and complement the current chemotherapy of TB. (C) 2012 Elsevier Ltd. All rights reserved.
• Nucleosides. 133. Synthesis of 5-alkenyl-1-(2-deoxy-2-fluoro-.beta.-D-arabinofuranosyl)cytosines and related pyrimidine nucleosides as potential antiviral agents
  作者：Michael E. Perlman、Kyoichi A. Watanabe、Raymond F. Schinazi、Jack J. Fox

  DOI：10.1021/jm00383a009

  日期：1985.6

  The synthesis of 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)cytosines with a halovinyl or vinyl substituent at C-5 was accomplished from the corresponding 5-iodo (FIAC, 1) and/or 5-chloromercuri nucleoside analogues with use of Li2PdCl4- and Pd(OAc)2-mediated coupling reactions. Thiation of the benzoylated derivative of the 5-ethyluracil nucleoside 3 followed by S-methylation and then ammonolysis

  由相应的5-碘（FIAC，1）和/或5-氯汞，完成在C-5上具有卤乙烯基或乙烯基取代基的1-（2-脱氧-2-氟-β-D-阿拉伯呋喃糖基）胞嘧啶的合成Li2PdCl4-和Pd（OAc）2介导的偶联反应的核苷类似物。对5-乙基尿嘧啶核苷3的苯甲酰化衍生物进行硫代化，然后进行S-甲基化，然后进行氨解，得到了5-乙基-2'-氟-ara-C。5-乙炔基-2'-氟代-ara-C（19a）和5-乙炔基-2'-氟代-ara-U（19b）也分别通过PdII / CuI与（三甲基甲硅烷基）乙炔催化偶联。通过使用H 2 O / Me 2 SO对初始偶联产物进行选择性糖脱保护，可以分离出相应的5- [2-（三甲基甲硅烷基）乙炔基]衍生物18a和18b。大多数新化合物在体外均表现出针对HSV-1和HSV-2的活性，已知的相应的较早合成的5-链烯基尿嘧啶核苷也是如此。5-乙烯基胞嘧啶核苷10和尿嘧啶核苷分别对HSV-1（ED90分别为0