齐夫多定相关物质B | 25526-94-7

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 中文名称: 齐夫多定相关物质B
• 中文别名: 叠氮胸苷相关物质B；齐多夫定杂质B
• 英文名称: 3'-Desoxy-3'-chlor-thymidin
• 英文别名: 3'-Chloro-3'-deoxythymidine；1-[(2R,4S,5R)-4-chloro-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 25526-94-7
• 化学式: C₁₀H₁₃ClN₂O₄
• 分子量: 260.677
• InChiKey: KQVJDKGDGLWBQT-XLPZGREQSA-N

物化性质

• 熔点：
  180-182 °C
• 密度：
  1.48±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  齐夫多定相关物质B 在 N-甲基咪唑 、 triisopropylbenzenesulfochloride 作用下， 以 吡啶 、 二氯甲烷 、 三氟乙酸 为溶剂， 反应 0.2h， 生成 Phosphoric acid (2R,3S,5R)-5-(6-benzoylamino-purin-9-yl)-2-hydroxymethyl-tetrahydro-furan-3-yl ester (2R,3S,5R)-3-chloro-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethyl ester 4-chloro-phenyl ester
  参考文献：
  名称：

  Rosenthal, Andre; Cech, Dieter; Veiko, Vladimir P., Zeitschrift fur Chemie, 1983, vol. 23, # 5, p. 178 - 179

  摘要：

  DOI：
• 作为产物：
  描述：

  3'-氯-3'-脱氧-5'-O-三苯甲基胸苷 在 水 、 溶剂黄146 作用下， 反应 0.5h， 以57%的产率得到齐夫多定相关物质B
  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

• DYATKINA, N. B.;ATRAZHEVA, E. D.;ALEKSANDROVA, L. A.;KRAEVSKIJ, A. A.;FON+, BIOORGAN. XIMIYA, 14,(1988) N 6, 815-819
  作者：DYATKINA, N. B.、ATRAZHEVA, E. D.、ALEKSANDROVA, L. A.、KRAEVSKIJ, A. A.、FON+

  DOI：——

  日期：——
• 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.
• Rosenthal, Andre; Cech, Dieter; Veiko, Vladimir P., Zeitschrift fur Chemie, 1983, vol. 23, # 5, p. 178 - 179
  作者：Rosenthal, Andre、Cech, Dieter、Veiko, Vladimir P.、Shabarova, Zoe A.

  DOI：——

  日期：——