2',3'-didehydro-3'-deoxythymidine 5'-O-hemisuccinate | 152336-78-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: 2',3'-didehydro-3'-deoxythymidine 5'-O-hemisuccinate
• 英文别名: 2',3'-didehydro-5'-O-hemisuccinate-3'-deoxythymidine；5'-hemisuccinyl-2',3'-didehydro-3'-deoxythymidine；5'-hemisuccinyl D4T；4-[[(2S,5R)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-2,5-dihydrofuran-2-yl]methoxy]-4-oxobutanoic acid
• CAS: 152336-78-2
• 化学式: C₁₄H₁₆N₂O₇
• 分子量: 324.29
• InChiKey: XSIDKCKUDIUNIL-VHSXEESVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  122
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2',3'-didehydro-3'-deoxythymidine 5'-O-hemisuccinate 在 buffer 作用下， 以 乙醇 为溶剂， 生成 司他夫定
  参考文献：
  名称：

  2'，3'-二氢-3'-脱氧胸苷的前药。

  摘要：

  合成了6种2'，3'-didehydro-3'-脱氧胸苷（D4T）的酯前药，并对其理化性质进行了评估。观察到明显差异。所有前药在2-7的pH范围内化学稳定。在所有情况下，在四个大鼠酶系统（血浆，肝，十二指肠和肾脏）中都观察到了这些酯的水解，并再生了D4T。将D4T或前药口服给予大鼠，并测量D4T和相应的前药的血浆浓度。静脉内给药后D4T的半衰期为35.9分钟。由终期计算的半衰期和口服D4T后血浆中的最大浓度分别为35.9分钟和48.4 microM。口服前药（用水或橄榄油作为溶剂）后，

  DOI：

  10.1002/jps.2600821210
• 作为产物：
  描述：

  5’-苯甲酰基-2’,3’-二脱氢-3’-脱氧胸腺嘧啶 在 buffer 作用下， 以 吡啶 、 乙醇 为溶剂， 生成 2',3'-didehydro-3'-deoxythymidine 5'-O-hemisuccinate
  参考文献：
  名称：

  2'，3'-二氢-3'-脱氧胸苷的前药。

  摘要：

  合成了6种2'，3'-didehydro-3'-脱氧胸苷（D4T）的酯前药，并对其理化性质进行了评估。观察到明显差异。所有前药在2-7的pH范围内化学稳定。在所有情况下，在四个大鼠酶系统（血浆，肝，十二指肠和肾脏）中都观察到了这些酯的水解，并再生了D4T。将D4T或前药口服给予大鼠，并测量D4T和相应的前药的血浆浓度。静脉内给药后D4T的半衰期为35.9分钟。由终期计算的半衰期和口服D4T后血浆中的最大浓度分别为35.9分钟和48.4 microM。口服前药（用水或橄榄油作为溶剂）后，

  DOI：

  10.1002/jps.2600821210

文献信息

• Benzophenone-nucleoside derivatives as telomerase inhibitors: Design, synthesis and anticancer evaluation in vitro and in vivo
  作者：Jing Bo Shi、Liu Zeng Chen、Yang Wang、Cheng Xiou、Wen Jian Tang、Hai Pin Zhou、Xin Hua Liu、Qi Zheng Yao

  DOI：10.1016/j.ejmech.2016.09.011

  日期：2016.11

  Based on telomerase, thirteen novel phenstatin moiety linked stavudine derivatives (8a∼8e and 11a∼11f) were synthesized. The structures were determined by NMR and TOF-HRMS. The screening results showed that some compounds had better anti-cancer activity in vivo and in vitro. Among them, Compound 8d showed high inhibitory activity against telomerase and showed good antiproliferative activity against

  基于端粒酶，13新颖phenstatin部分连接司他夫定衍生物（8A〜8E和图11A〜11F）的合成。通过NMR和TOF-HRMS确定结构。筛选结果表明，某些化合物在最好的抗癌活性的体内和在体外。其中，化合物8d对端粒酶具有很高的抑制活性，对具有IC 50的SGC-7901细胞也具有良好的抗增殖活性诱导细胞周期停滞在G2期，其值为0.77μM。它也可以改善SGC-7901细胞的凋亡，线粒体膜电位测定表明MMP的耗散可能参与了标题化合物诱导的细胞凋亡。体内研究表明，化合物8d显示出有效的抗癌活性，并抑制了肿瘤的生长。
• Nasal Absorption of 2',3'-Didehydro-3'-deoxythymidine (D4T) and Its Esters in Rats.
  作者：Toshiyuki YAJIMA、Tetsuya HASEGAWA、Kazuhiko JUNI、Mineo SANEYOSHI、Takeo KAWAGUCHI

  DOI：10.1248/bpb.19.1234

  日期：——

  Nasal absorption of 2', 3'-didehydro-3'-deoxythymidine (D4T) and its esters (5'-acetyl D4T : C2-D4T and 5'-hemisuccinyl D4T : Suc-D4T) was investigated in rats. Bioavailability of D4T following intranasal (i.n.) administration was 98.0%, and the elimination from plasma was as rapid as that following intravenous administration of D4T. There seemed to be complete and rapid absorption of D4T from the nasal cavity. The plasma concentration-time profile of D4T following i.n. administration of C2-D4T was almost the same as that after administration of D4T itself. This suggests that C2-D4T was rapidly absorbed from the nasal cavity, and that some amount of dosing C2-D4T was hydrolyzed to D4T before entering the systemic circulation. In contrast, Suc-D4T showed slower absorption in the i.n. administration, and the plasma D4T level was maintained for a long period.

  研究了大鼠对 2'，3'-双脱氢-3'-脱氧胸苷（D4T）及其酯类（5'-乙酰基 D4T：C2-D4T 和 5'-hemisuccinyl D4T：Suc-D4T）的鼻腔吸收情况。鼻内给药后，D4T 的生物利用率为 98.0%，从血浆中消除的速度与静脉给药后一样快。鼻腔似乎可以完全、快速地吸收 D4T。静脉注射 C2-D4T 后，D4T 的血浆浓度-时间曲线与服用 D4T 本身后的血浆浓度-时间曲线几乎相同。这表明，C2-D4T 从鼻腔中被迅速吸收，在进入全身循环之前，一定剂量的 C2-D4T 被水解为 D4T。相比之下，Suc-D4T 在鼻腔给药时吸收较慢，血浆中的 D4T 水平维持了很长时间。
• Zhou, Xiao-Jian; Chakboub, Hassan; Ferrua, Bernard, Antimicrobial Agents and Chemotherapy, 1996, vol. 40, # 6, p. 1472 - 1475
  作者：Zhou, Xiao-Jian、Chakboub, Hassan、Ferrua, Bernard、Moravek, Joseph、Guedj, Roger、Sommadossi, Jean-Pierre

  DOI：——

  日期：——
• Yajima, Toshiyuki; Juni, Kazuhiko; Saneyoshi, Mineo, Biological and pharmaceutical bulletin, 1998, vol. 21, # 3, p. 272 - 277
  作者：Yajima, Toshiyuki、Juni, Kazuhiko、Saneyoshi, Mineo、Hasegawa, Tetsuya、Kawaguchi, Takeo

  DOI：——

  日期：——
• Prodrugs of 2’,3’-Didehydro-3’-deoxythymidine
  作者：Tetsuya Hasegawa、Toshinobu Seki、Kazuhiko Juni、Mineo Saneyoshi、Takeo Kawaguchi

  DOI：10.1002/jps.2600821210

  日期：1993.12

  ester prodrugs of 2',3'-didehydro-3'-deoxythymidine (D4T) were synthesized, and their physicochemical properties were evaluated. Marked differences were observed. All of the prodrugs were chemically stable within the pH range 2-7. Hydrolysis of these esters was observed in all cases for four rat enzyme systems (plasma, liver, duodenum, and kidney), with D4T being regenerated. D4T or the prodrug was administered

  合成了6种2'，3'-didehydro-3'-脱氧胸苷（D4T）的酯前药，并对其理化性质进行了评估。观察到明显差异。所有前药在2-7的pH范围内化学稳定。在所有情况下，在四个大鼠酶系统（血浆，肝，十二指肠和肾脏）中都观察到了这些酯的水解，并再生了D4T。将D4T或前药口服给予大鼠，并测量D4T和相应的前药的血浆浓度。静脉内给药后D4T的半衰期为35.9分钟。由终期计算的半衰期和口服D4T后血浆中的最大浓度分别为35.9分钟和48.4 microM。口服前药（用水或橄榄油作为溶剂）后，