1-β-D-arabinofuranosyl-4-thiouracil | 32754-06-6

• 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-β-D-arabinofuranosyl-4-thiouracil
• 英文别名: Arabino-4-thiouridin；1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-sulfanylidenepyrimidin-2-one
• CAS: 32754-06-6
• 化学式: C₉H₁₂N₂O₅S
• 分子量: 260.271
• InChiKey: ZLOIGESWDJYCTF-CCXZUQQUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 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：
  134
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  阿糖尿苷 在 劳森试剂 、 4-二甲氨基吡啶 、 氨 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 11.0h， 生成 1-β-D-arabinofuranosyl-4-thiouracil
  参考文献：
  名称：

  Growth Inhibition of Mycobacterium bovis, Mycobacterium tuberculosis and Mycobacterium avium In Vitro:  Effect of 1-β-d-2‘-Arabinofuranosyl and 1-(2‘-Deoxy-2‘-fluoro-β-d-2‘-ribofuranosyl) Pyrimidine Nucleoside Analogs

  摘要：

  The resurgence of tuberculosis and the emergence of multiple-drug-resistant strains of Mycobacteria necessitate the search for new classes of antimycobacterial agents. We synthesized a series of 1-beta-D-2'-arabinofuranosyl and 1-(2'-deoxy-2'-fluoro-beta-D-ribofuranosyl) pyrimidine nucleosides possessing diverse sets of alkynyl, alkenyl, alkyl, and halo substituents at the C-5 position of the uracil and investigated their effect on activity against M. tuberculosis, M. bovis, and M. avium. Among these molecules, 5-alkynyl-substituted derivatives emerged as potent inhibitors of M. bovis, M. tuberculosis, and M. avium. Nucleosides 1-beta-D-2'-arabinofuranosyl-5-dodecynyluracil (5), 1-(2'-deoxy-2'-fluoro-beta-D-ribofuranosyl)-5-dodecynyluracil (24), and 1-(2'-deoxy-2'-fluoro-beta-D-ribofuranosyl)-5-tetradecynyluracil (25) showed the highest antimycobacterial potency against M. bovis and M. tuberculosis. The MIC90 exhibited by compounds 5,24, and 25 was similar or close to that of the reference drug rifampicin. The most active compounds 5, 24, and 25 were also found to retain sensitivity against a rifampicin-resistant strain of M. tuberculosis H37Rv at similar concentrations. Some of these analogs also revealed in vitro antimicrobial effect against several other gram-positive pathogens.

  DOI：

  10.1021/jm0703901

文献信息

• Growth Inhibition of <i>Mycobacterium </i><i>bovis</i>, <i>Mycobacterium </i><i>tuberculosis</i> and <i>Mycobacterium </i><i>avium</i> In Vitro:  Effect of 1-β-<scp>d</scp>-2‘-Arabinofuranosyl and 1-(2‘-Deoxy-2‘-fluoro-β-<scp>d</scp>-2‘-ribofuranosyl) Pyrimidine Nucleoside Analogs
  作者：Monika Johar、Tracey Manning、Christopher Tse、Nancy Desroches、B. Agrawal、Dennis Y. Kunimoto、Rakesh Kumar

  DOI：10.1021/jm0703901

  日期：2007.7.1

  The resurgence of tuberculosis and the emergence of multiple-drug-resistant strains of Mycobacteria necessitate the search for new classes of antimycobacterial agents. We synthesized a series of 1-beta-D-2'-arabinofuranosyl and 1-(2'-deoxy-2'-fluoro-beta-D-ribofuranosyl) pyrimidine nucleosides possessing diverse sets of alkynyl, alkenyl, alkyl, and halo substituents at the C-5 position of the uracil and investigated their effect on activity against M. tuberculosis, M. bovis, and M. avium. Among these molecules, 5-alkynyl-substituted derivatives emerged as potent inhibitors of M. bovis, M. tuberculosis, and M. avium. Nucleosides 1-beta-D-2'-arabinofuranosyl-5-dodecynyluracil (5), 1-(2'-deoxy-2'-fluoro-beta-D-ribofuranosyl)-5-dodecynyluracil (24), and 1-(2'-deoxy-2'-fluoro-beta-D-ribofuranosyl)-5-tetradecynyluracil (25) showed the highest antimycobacterial potency against M. bovis and M. tuberculosis. The MIC90 exhibited by compounds 5,24, and 25 was similar or close to that of the reference drug rifampicin. The most active compounds 5, 24, and 25 were also found to retain sensitivity against a rifampicin-resistant strain of M. tuberculosis H37Rv at similar concentrations. Some of these analogs also revealed in vitro antimicrobial effect against several other gram-positive pathogens.