1-(3-bromo-2,3-dideoxy-β-D-erythro-pentofuranosyl)thymine | 99785-51-0

• 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-erythro-pentofuranosyl)thymine
• 英文别名: 3'-bromo-3-deoxythymidine；3'-bromo-3'-deoxy-thymidine；3'-Brom-3'-deoxy-thymidin；Thymidine, 3'-bromo-3'-deoxy-；1-[(2R,4S,5R)-4-bromo-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 99785-51-0
• 化学式: C₁₀H₁₃BrN₂O₄
• 分子量: 305.128
• InChiKey: VSYTWOCFTNWUQF-XLPZGREQSA-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：
  0.6
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  4

制备方法与用途

3'-溴-3'-脱氧胸苷是一种嘌呤核苷类似物，具有广泛的抗肿瘤活性，尤其针对惰性淋巴系统恶性肿瘤。其抗癌机制主要通过抑制DNA合成和诱导细胞凋亡来实现。

反应信息

• 作为反应物：
  描述：

  1-(3-bromo-2,3-dideoxy-β-D-erythro-pentofuranosyl)thymine 在 sodium azide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 齐多夫定
  参考文献：
  名称：

  抗疟药萘醌类。通过点击化学、体外活性、对接 PfDHODH 和 SAR 合成基于lapachol的化合物

  摘要：

  Lapachol 是一种丰富的异戊二烯基萘醌，存在于巴西紫葳科植物中，尽管效果适中，但在过去临床上被用作抗疟药。为了寻找可能更好的抗疟药，通过对 lapacol 进行化学改性合成了一系列 1,2,3-三唑衍生物。羟基的烷基化得到其炔丙基醚，通过铜催化的环加成 （CuAAC） 点击化学与不同的有机叠氮化物，得到 17 种萘喹啉酰三唑衍生物。评价 所有合成化合物对耐氯喹恶性疟原虫 （W2） 的体外活性和对 HepG2 细胞的细胞毒性。含有萘喹酰三唑部分的化合物显示出比 lapachol 更高的抗疟活性 （IC50 123.5 μM），选择性指数 （SI） 值在 4.5-197.7 范围内。对 lapachol、atovaquone 和所有新合成的化合物进行分子对接模拟，以与 PfDHODH 相互作用，PfDHODH 是寄生虫呼吸链的线粒体酶，对从头嘧啶生物合成至关重要。萘喹啉基三唑衍生物与 PfDHODH

  DOI：

  10.1016/j.ejmech.2017.12.051
• 作为产物：
  描述：

  1-(3-bromo-2,3-dideoxy-5-O-trityl-β-D-erythro-pentofuranosyl)thymine 在 水 、 溶剂黄146 作用下， 反应 0.5h， 以36%的产率得到1-(3-bromo-2,3-dideoxy-β-D-erythro-pentofuranosyl)thymine
  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.
• Antimalarial naphthoquinones. Synthesis via click chemistry, in vitro activity , docking to Pf DHODH and SAR of lapachol-based compounds
  作者：Geraldo Célio Brandão、Franciele C. Rocha Missias、Lucas Miquéias Arantes、Luciana Ferreira Soares、Kuldeep K. Roy、Robert J. Doerksen、Alaide Braga de Oliveira、Guilherme Rocha Pereira

  DOI：10.1016/j.ejmech.2017.12.051

  日期：2018.2

  different organic azides, afforded 17 naphthoquinonolyl triazole derivatives. All the synthetic compounds were evaluated for their in vitro activity against chloroquine resistant Plasmodium falciparum (W2) and for cytotoxicity to HepG2 cells. Compounds containing the naphthoquinolyl triazole moieties showed higher antimalarial activity than lapachol (IC50 123.5 μM) and selectivity index (SI) values

  Lapachol 是一种丰富的异戊二烯基萘醌，存在于巴西紫葳科植物中，尽管效果适中，但在过去临床上被用作抗疟药。为了寻找可能更好的抗疟药，通过对 lapacol 进行化学改性合成了一系列 1,2,3-三唑衍生物。羟基的烷基化得到其炔丙基醚，通过铜催化的环加成 （CuAAC） 点击化学与不同的有机叠氮化物，得到 17 种萘喹啉酰三唑衍生物。评价 所有合成化合物对耐氯喹恶性疟原虫 （W2） 的体外活性和对 HepG2 细胞的细胞毒性。含有萘喹酰三唑部分的化合物显示出比 lapachol 更高的抗疟活性 （IC50 123.5 μM），选择性指数 （SI） 值在 4.5-197.7 范围内。对 lapachol、atovaquone 和所有新合成的化合物进行分子对接模拟，以与 PfDHODH 相互作用，PfDHODH 是寄生虫呼吸链的线粒体酶，对从头嘧啶生物合成至关重要。萘喹啉基三唑衍生物与 PfDHODH