1-(3-chloro-2,3-dideoxy-5-O-trityl-β-D-threo-pentofuranosyl)-5-fluorouracil | 1227358-30-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 1-(3-chloro-2,3-dideoxy-5-O-trityl-β-D-threo-pentofuranosyl)-5-fluorouracil
• 英文别名: 1-[(2R,4R,5R)-4-chloro-5-(trityloxymethyl)oxolan-2-yl]-5-fluoropyrimidine-2,4-dione
• CAS: 1227358-30-6
• 化学式: C₂₈H₂₄ClFN₂O₄
• 分子量: 506.961
• InChiKey: NWZBUQWBFBHCEZ-QLBJFCOMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(3-chloro-2,3-dideoxy-5-O-trityl-β-D-threo-pentofuranosyl)-5-fluorouracil 在 水 、 溶剂黄146 作用下， 反应 0.5h， 以79%的产率得到1-(3-chloro-2,3-dideoxy-β-D-threo-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
• 作为产物：
  描述：

  5-氟-1-[4-羟基-5-[三(苯基)甲氧基甲基]四氢呋喃-2-基]嘧啶-2,4-二酮 在 四氯化碳 、 三苯基膦 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以57%的产率得到1-(3-chloro-2,3-dideoxy-5-O-trityl-β-D-threo-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.