1-(3-bromo-2,3-dideoxy-β-D-threo-pentofuranosyl)-5-fluorouracil | 1227358-28-2

• 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-(3-bromo-2,3-dideoxy-β-D-threo-pentofuranosyl)-5-fluorouracil
• 英文别名: 1-[(2R,4R,5R)-4-bromo-5-(hydroxymethyl)tetrahydrofuran-2-yl]-5-fluoro-pyrimidine-2,4-dione；1-[(2R,4R,5R)-4-bromo-5-(hydroxymethyl)oxolan-2-yl]-5-fluoropyrimidine-2,4-dione
• CAS: 1227358-28-2
• 化学式: C₉H₁₀BrFN₂O₄
• 分子量: 309.092
• InChiKey: TZAOSPUOPDCJLV-QPPQHZFASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(3-bromo-2,3-dideoxy-β-D-threo-pentofuranosyl)-5-fluorouracil 在 dipotassium peroxodisulfate 、 ruthenium(III) chloride trihydrate 、 potassium hydroxide 作用下， 以 水 为溶剂， 反应 8.0h， 以67%的产率得到1-(3,4-didehydro-2,3-dideoxy-5-oxo-β-D-pentofuranosyl)-5-fluorouracil
  参考文献：
  名称：

  4'-Modified Pyrimidine Nucleosides as Potential Anti-hepatitis C Virus (HCV) Agents

  摘要：

  在此，我们研究了具有 4'- 羧基官能团的新型嘧啶核苷（6-10、13 和 15）作为抗HCV 药物。在这一类新化合物中，7、9、10 和 15 的体外抗HCV 活性类似于或优于已知的抗HCV 药物利巴韦林。在这项工作中，我们还意外地发现了一种 3'-thiacytidine 的 3'-sulfoxide 类似物（16），它是在合成 15 的过程中作为副产品获得的，是一种有效的 HCV 复制抑制剂，其浓度与利巴韦林相似。在测试的最高浓度范围内，未发现所研究化合物具有可检测到的体外细胞毒性。

  DOI：

  10.2174/1570180811666140401184856
• 作为产物：
  描述：

  5'-O-trityl-3'-O-mesyl-2'-deoxy-5-fluorouridine 在 lithium bromide 作用下， 以 乙腈 为溶剂， 反应 22.0h， 以24%的产率得到1-(3-bromo-2,3-dideoxy-β-D-erythro-pentofuranosyl)-5-fluorouracil
  参考文献：
  名称：

  3′-Bromo Analogues of Pyrimidine Nucleosides as a New Class of Potent Inhibitors ofMycobacterium tuberculosis

  摘要：

  Tuberculosis (TB) is a major health problem worldwide. We herein report a new class of pyrimidine nucleosides as potent inhibitors of Mycobacterium tuberculosis (M. tuberculosis). Various 2'- or 3'-halogeno derivatives of pyrimidine nucleosides containing uracil, 5-fluorouracil, and thymine bases were synthesized and evaluated for antimycobacterial activities. Among the compounds tested, 3'-bromo-3'-deoxy-arabinofuranosylthymine (3') was the most effective antituberculosis agent in the in vitro assays against wild-type M. tuberculosis strain (H37Ra) (MIC50 = 1 mu g/mL) as well as drug-resistant (H37Rv) (rifampicin-resistant and isoniazid-resistant) strains of M. tuberculosis (MIC50 = 1-2 mu g/mL). Compound 3' also inhibited intracellular M. tuberculosis in a human monocytic cell line infected with H37Ra, demonstrating higher activity against intramacrophagic mycobacteria (80% reduction at 10 mu g/mL concentration) than extracellular mycobacteria (75% reduction at 10 mu g/mL concentration). In contrast, pyrimidine nucleosides possessing 5-fluorouracil base were weak inhibitors of M. tuberculosis. No cytotoxicity was found up to the highest concentration of compounds tested (CC50 > 100-200 mu g/mL) against a human cell line. Overall, these encouraging results substantiate the potential of this new class of compounds as promising antituberculosis agents.

  DOI：

  10.1021/jm100165w

文献信息

• 3′-Bromo Analogues of Pyrimidine Nucleosides as a New Class of Potent Inhibitors of<i>Mycobacterium tuberculosis</i>
  作者：Neeraj Shakya、Naveen C. Srivastav、Nancy Desroches、Babita Agrawal、Dennis Y. Kunimoto、Rakesh Kumar

  DOI：10.1021/jm100165w

  日期：2010.5.27

  Tuberculosis (TB) is a major health problem worldwide. We herein report a new class of pyrimidine nucleosides as potent inhibitors of Mycobacterium tuberculosis (M. tuberculosis). Various 2'- or 3'-halogeno derivatives of pyrimidine nucleosides containing uracil, 5-fluorouracil, and thymine bases were synthesized and evaluated for antimycobacterial activities. Among the compounds tested, 3'-bromo-3'-deoxy-arabinofuranosylthymine (3') was the most effective antituberculosis agent in the in vitro assays against wild-type M. tuberculosis strain (H37Ra) (MIC50 = 1 mu g/mL) as well as drug-resistant (H37Rv) (rifampicin-resistant and isoniazid-resistant) strains of M. tuberculosis (MIC50 = 1-2 mu g/mL). Compound 3' also inhibited intracellular M. tuberculosis in a human monocytic cell line infected with H37Ra, demonstrating higher activity against intramacrophagic mycobacteria (80% reduction at 10 mu g/mL concentration) than extracellular mycobacteria (75% reduction at 10 mu g/mL concentration). In contrast, pyrimidine nucleosides possessing 5-fluorouracil base were weak inhibitors of M. tuberculosis. No cytotoxicity was found up to the highest concentration of compounds tested (CC50 > 100-200 mu g/mL) against a human cell line. Overall, these encouraging results substantiate the potential of this new class of compounds as promising antituberculosis agents.
• 4'-Modified Pyrimidine Nucleosides as Potential Anti-hepatitis C Virus (HCV) Agents
  作者：Neeraj Shakya、Satish Vedi、Chao Liang、Babita Agrawal、Rakesh Kumar

  DOI：10.2174/1570180811666140401184856

  日期：2014.6

  Herein, we have investigated novel pyrimidine nucleosides bearing a 4’-carboxyl functionality (6-10, 13 and 15) as anti-HCV agents. In this new class of compounds, 7, 9, 10 and 15 demonstrated in vitro anti-HCV activity similar to or better than a known anti-HCV drug, ribavirin. In this work, we also, surprisingly, identified a 3’-sulfoxide analog of 3’-thiacytidine (16), obtained as a side product during the synthesis of 15, as a potent inhibitor of HCV replication at the concentration similar to that of ribavirin. No detectable in vitro cytotoxicity was observed for the investigated compounds up to the highest concentration tested.

  在此，我们研究了具有 4'- 羧基官能团的新型嘧啶核苷（6-10、13 和 15）作为抗HCV 药物。在这一类新化合物中，7、9、10 和 15 的体外抗HCV 活性类似于或优于已知的抗HCV 药物利巴韦林。在这项工作中，我们还意外地发现了一种 3'-thiacytidine 的 3'-sulfoxide 类似物（16），它是在合成 15 的过程中作为副产品获得的，是一种有效的 HCV 复制抑制剂，其浓度与利巴韦林相似。在测试的最高浓度范围内，未发现所研究化合物具有可检测到的体外细胞毒性。