1-(3-iodo-2,3-dideoxy-β-D-erythro-pentofuranosyl)-5-fluorouracil | 1227358-35-1

• 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-iodo-2,3-dideoxy-β-D-erythro-pentofuranosyl)-5-fluorouracil
• 英文别名: 5-fluoro-1-[(2R,4S,5R)-5-(hydroxymethyl)-4-iodo-tetrahydrofuran-2-yl]pyrimidine-2,4-dione；5-fluoro-1-[(2R,4S,5R)-5-(hydroxymethyl)-4-iodooxolan-2-yl]pyrimidine-2,4-dione
• CAS: 1227358-35-1
• 化学式: C₉H₁₀FIN₂O₄
• 分子量: 356.092
• InChiKey: VPSRSXDHZYPJPY-RRKCRQDMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 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

• 作为产物：
  描述：

  5'-O-trityl-3'-O-mesyl-2'-deoxy-5-fluorouridine 在 sodium iodide 、 水 、 溶剂黄146 作用下， 以 乙二醇二甲醚 为溶剂， 反应 20.5h， 以45%的产率得到1-(3-iodo-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.