1-beta-D-阿拉伯呋喃糖基-4-癸酰氨基嘧啶-2(1H)-酮 | 55726-41-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 中文名称: 1-beta-D-阿拉伯呋喃糖基-4-癸酰氨基嘧啶-2(1H)-酮
• 英文名称: N4-decanoyl-4-amino-1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one
• 英文别名: 1-β-D-arabinofuranosyl-4-decanoylamino-1H-pyrimidin-2-one；N4-Caproyl-1-β-D-arabinofuranosylcytosine；N⁴-Capryl-1-β-D-arabinofuranosylcytosin；Cytosine, 1-beta-D-arabinofuranosyl-N(sup 4)-decanoyl-；N-[1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-oxopyrimidin-4-yl]decanamide
• CAS: 55726-41-5
• 化学式: C₁₉H₃₁N₃O₆
• 分子量: 397.472
• InChiKey: KZOQNDVOLFAXQQ-NKGKWGDASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  132
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  正癸酸 在 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.33h， 生成 1-beta-D-阿拉伯呋喃糖基-4-癸酰氨基嘧啶-2(1H)-酮
  参考文献：
  名称：

  In-vitro transdermal penetration of cytarabine and its N4-alkylamide derivatives

  摘要：

  Objectives The aim of this study was to synthesise and determine the transdermal penetration of cytarabine alkylamide derivatives and assess the correlation of flux with physicochemical properties.Methods The alkylamide derivatives of cytarabine were synthesised by acylation at the N4-amino group by the mixed anhydride method. The in-vitro permeation studies were performed using the Franz diffusion cell methodology. Furthermore, partition coefficients (n-octanol-water) and aqueous solubility of the N4-alkylamide derivatives of cytarabine were determined in order to obtain information about their lipophilicity and hydrophilicity.Key findings The N4-alkylamides of cytarabine (acetyl, butanoyl, hexanoyl, octanoyl, and decanoyl derivatives) showed decreased hydrophilicity and increased lipophilicity. The log D values of the alkylamides were higher than that of the parent compound and increased linearly as the alkyl chain lengthened. N4-hexanoyl-4-amino-1-[(2R,3S,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl] pyrimidin-2-one) showed the highest median steady-state flux (J(ss)) of 89.0 nmol/cm(2) per h in the series, which shows a high statistical difference with the parent compound flux value (3.70 nmol/cm(2) per h).Conclusions The prodrug approach appears to be a promising strategy for the enhancement of transdermal penetration of cytarabine.

  DOI：

  10.1211/jpp.62.06.0012

文献信息

• 一种新型阿糖胞苷前药DA-Ara纳米组装体的制备方法及应用
  申请人：山东大学

  公开号：CN108409819A

  公开（公告）日：2018-08-17

  本发明公开了一种新型阿糖胞苷前药纳米组装体制备方法和应用。本发明选取生物相容性的癸酸为疏水材料，与阿糖胞苷共价结合，合成一种新型阿糖胞苷两亲性小分子前药癸酸‑阿糖胞苷(DA‑Ara)，经纳米沉淀法，前药可在水中自组装形成纳米棒，用水重新分散，可得到稳定性好的纳米口服给药制剂。体外细胞毒性实验结果显示，前药DA‑Ara对人慢性细胞白血病细胞K562展现了较强的敏感性，抑制细胞起效快，作用持久，细胞毒性更强。前药口服制剂载药量高，纳米混悬液浓度高，保存时间长且稳定性好，更易于生产的储存与运输，安全性好，为阿糖胞苷口服给药形式提供广阔应用前景。
• ISIDA, TORAO;AKIYAMA, MINORU;OISI, DZYUNITI
  作者：ISIDA, TORAO、AKIYAMA, MINORU、OISI, DZYUNITI

  DOI：——

  日期：——
• In-vitro transdermal penetration of cytarabine and its N4-alkylamide derivatives
  作者：Lesetja J. Legoabe、Jaco C. Breytenbach、David D. N'Da、J. Wilma Breytenbach

  DOI：10.1211/jpp.62.06.0012

  日期：2010.6

  Objectives The aim of this study was to synthesise and determine the transdermal penetration of cytarabine alkylamide derivatives and assess the correlation of flux with physicochemical properties.Methods The alkylamide derivatives of cytarabine were synthesised by acylation at the N4-amino group by the mixed anhydride method. The in-vitro permeation studies were performed using the Franz diffusion cell methodology. Furthermore, partition coefficients (n-octanol-water) and aqueous solubility of the N4-alkylamide derivatives of cytarabine were determined in order to obtain information about their lipophilicity and hydrophilicity.Key findings The N4-alkylamides of cytarabine (acetyl, butanoyl, hexanoyl, octanoyl, and decanoyl derivatives) showed decreased hydrophilicity and increased lipophilicity. The log D values of the alkylamides were higher than that of the parent compound and increased linearly as the alkyl chain lengthened. N4-hexanoyl-4-amino-1-[(2R,3S,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl] pyrimidin-2-one) showed the highest median steady-state flux (J(ss)) of 89.0 nmol/cm(2) per h in the series, which shows a high statistical difference with the parent compound flux value (3.70 nmol/cm(2) per h).Conclusions The prodrug approach appears to be a promising strategy for the enhancement of transdermal penetration of cytarabine.