(-)-(2S,4S)-1-[2-(hydroxymethyl)-1,3-dioxolan-4-yl]-4-N-benzoyl-cytosine

• 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: (-)-(2S,4S)-1-[2-(hydroxymethyl)-1,3-dioxolan-4-yl]-4-N-benzoyl-cytosine
• 英文别名: N-[1-[(2S,4S)-2-(hydroxymethyl)-1,3-dioxolan-4-yl]-2-oxopyrimidin-4-yl]benzamide
• 化学式: C₁₅H₁₅N₃O₅
• 分子量: 317.301
• InChiKey: KGVNFKGEYSUKCS-STQMWFEESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  、 、 、 (-)-(2S,4S)-1-[2-(hydroxymethyl)-1,3-dioxolan-4-yl]-4-N-benzoyl-cytosine 、 、 、 、 (-)-(2S,4S)-1-[2-(hydroxymethyl)-1,3-dioxolan-4-yl]-4-N-(p-fluorobenzoyl)-cytosine 、 、 、 、 (-)-(2S,4S)-1-[2-(hydroxymethyl)-1,3-dioxolan-4-yl]-4-N-(p-chlorobenzoyl)-cytosine 、 、 、 、 (-)-(2S,4S)-1-[2-(hydroxymethyl)-1,3-dioxolan-4-yl]-4-N-(p-bromobenzoyl)-cytosine 、 、 、 、 (-)-(2S,4S)-1-[2-(hydroxymethyl)-1,3-dioxolan-4-yl]-4-N-(p-methoxybenzoyl)-cytosine 、 、 、 、 (-)-(2S,4S)-1-[2-(hydroxymethyl)-1,3-dioxolan-4-yl]-4-N-(2,4-dichlorobenzoyl)-cytosine 、 、 、 以 水 、 甲醇 为溶剂， 生成 (-)-(2S,4S)-1-[2-(hydroxymethyl)-1,3-dioxolan-4-yl]-4-N-cyclohexyl-cytosine
  参考文献：
  名称：

  L-ODDC PRODRUGS FOR CANCER

  摘要：

  大多数核苷类抗癌药物的主要缺点源于它们亲水性的特性，这种特性需要高剂量和频繁的静脉注射。与其他核苷类抗肿瘤药物不同，托沙他滨似乎主要通过被动扩散进入肿瘤细胞，而不是使用核苷转运体，尽管这可能是模型相关的。因此，在本研究中，使用并行方法合成了二十种托沙他滨前药库，以评估前药的亲脂性与其抗肿瘤活性之间的关系。对两种非小细胞肺癌细胞系（A549和SW1573）和胰腺细胞系的前药进行生物评价，明显显示出比托沙他滨更好的抗肿瘤活性，IC50值在纳摩尔范围内。

  公开号：

  US20100266674A1
• 作为产物：
  描述：

  苯甲酸酐 、 曲沙他滨 以 甲醇 为溶剂， 反应 6.0h， 以85%的产率得到(-)-(2S,4S)-1-[2-(hydroxymethyl)-1,3-dioxolan-4-yl]-4-N-benzoyl-cytosine
  参考文献：
  名称：

  In Vitro Optimization of Non-Small Cell Lung Cancer Activity with Troxacitabine, l-1,3-Dioxolane-cytidine, Prodrugs

  摘要：

  l-1,3-Dioxolane-cytidine, a potent anticancer agent against leukemia, has limited efficacy against solid tumors, perhaps due to its hydrophilicity. Herein, a library of prodrugs were synthesized to optimize in vitro antitumor activity against non-small cell lung cancer. N-4-Substituted fatty acid amide prodrugs of 10-16 carbon chain length demonstrated significantly improved antitumor activity over l-1,3-dioxolane-cytidine. These in vitro results suggest that the in vivo therapeutic efficacy of l-1,3-dioxolane-cytidine against solid tumors may be improved with prodrug strategies.

  DOI：

  10.1021/jm0612923

文献信息

• In Vitro Optimization of Non-Small Cell Lung Cancer Activity with Troxacitabine, <scp>l</scp>-1,3-Dioxolane-cytidine, Prodrugs
  作者：Marco Radi、Auke D. Adema、Jonathan R. Daft、Jong H. Cho、Eveline K. Hoebe、Lou-Ella M. M. Alexander、Godefridus J. Peters、Chung K. Chu

  DOI：10.1021/jm0612923

  日期：2007.5.1

  l-1,3-Dioxolane-cytidine, a potent anticancer agent against leukemia, has limited efficacy against solid tumors, perhaps due to its hydrophilicity. Herein, a library of prodrugs were synthesized to optimize in vitro antitumor activity against non-small cell lung cancer. N-4-Substituted fatty acid amide prodrugs of 10-16 carbon chain length demonstrated significantly improved antitumor activity over l-1,3-dioxolane-cytidine. These in vitro results suggest that the in vivo therapeutic efficacy of l-1,3-dioxolane-cytidine against solid tumors may be improved with prodrug strategies.
• L-ODDC PRODRUGS FOR CANCER
  申请人：Chu David C.K.

  公开号：US20100266674A1

  公开（公告）日：2010-10-21

  The main drawback in the use of most nucleoside anticancer agents originates from their hydrophilic nature, of which property requires a high and frequent dosage for an intravenous administration. Unlike other nucleoside anti-tumor agents, troxacitabine appears to predominantly enter tumor cells by passive diffusion rather then by using nucleoside transporters, although this may be model dependent. Accordingly, in the present work, a small library of twenty troxacitabine prodrugs has been synthesized using a parallel approach in order to evaluate the relationship between the lipophilicity of the prodrugs and their antitumor activity. Biological evaluation of the prodrugs on two non-small cell lung cancer cell lines (A549 and SW1573) and in pancreatic cell lines clearly showed better antitumor activity than that of troxacitabine, with IC 50 values in the nanomolar range.

  大多数核苷类抗癌药物的主要缺点源于它们亲水性的特性，这种特性需要高剂量和频繁的静脉注射。与其他核苷类抗肿瘤药物不同，托沙他滨似乎主要通过被动扩散进入肿瘤细胞，而不是使用核苷转运体，尽管这可能是模型相关的。因此，在本研究中，使用并行方法合成了二十种托沙他滨前药库，以评估前药的亲脂性与其抗肿瘤活性之间的关系。对两种非小细胞肺癌细胞系（A549和SW1573）和胰腺细胞系的前药进行生物评价，明显显示出比托沙他滨更好的抗肿瘤活性，IC50值在纳摩尔范围内。