S-(2-hydroxyethyl) 2,2,5-trimethyl-1,3-dioxane-5-carbothioate | 1068659-36-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: S-(2-hydroxyethyl) 2,2,5-trimethyl-1,3-dioxane-5-carbothioate
• CAS: 1068659-36-8
• 化学式: C₁₀H₁₈O₄S
• 分子量: 234.317
• InChiKey: PMSYRLKFKVDHGT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.03
• 重原子数：
  15.0
• 可旋转键数：
  3.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  55.76
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  S-(2-hydroxyethyl) 2,2,5-trimethyl-1,3-dioxane-5-carbothioate 、 双二异丙基氨基氯化磷 在 三乙胺 作用下， 以 乙醚 为溶剂， 以61%的产率得到S-[2-(2,2-dimethyl-1,3-dioxan-5-yl)propionyl]-2-thioethyl-di(N,N-diisopropylamino)phosphorobisamidite
  参考文献：
  名称：

  Special feature of mixed phosphotriester derivatives of cytarabine

  摘要：

  Despite the unquestionable therapeutic interest of bis(SATE) pronucleotides, a presystemic metabolism preventing the delivery of the prodrugs in target cancer cells or tumours may constitute a limitation to the in vivo development of such derivatives. In order to overcome these drawbacks several strategies have been envisaged and we report herein the application of the S-acyl-2-thioethyl (SATE) phenyl pronucleotide approach to the well-known cytotoxic nucleoside cytosine-1-beta-D-arabinofuranoside (cytarabine, araC). We describe modifications of the SATE moieties with the introduction of polar groups on the acyl residue, in order to study how these changes affect antitumoral activity and metabolic stability. Two different synthetic pathways were explored and lead to obtain the corresponding mixed derivatives in satisfactory yields. Cytotoxicity was studied in murine leukaemia cells L1210 as well as in cells derived from solid human tumours (Messa and MCF7). Biological evaluation of these compounds in cell culture experiments with nucleoside analogue-sensitive and resistant cell lines showed that the modified compounds were active at higher concentrations than unmodified cytarabine, yet were much able to partially reverse resistance due to deficient nucleoside transport or activation. These results can be correlated with an incomplete decomposition mechanism into the corresponding 5'-mononucleotide. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.07.038
• 作为产物：
  描述：

  2,2,5-三甲基-1,3-二恶烷-5-甲酸 、 2-巯基乙醇 在 N,N'-羰基二咪唑 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 2.5h， 以98%的产率得到S-(2-hydroxyethyl) 2,2,5-trimethyl-1,3-dioxane-5-carbothioate
  参考文献：
  名称：

  AZT的苯基磷酸三酯衍生物：SATE部分的变异。

  摘要：

  AZT（zidovudine; 3'-azido-2'，3'-二脱氧胸苷）在本文中描述。这些前核苷酸的特征在于在SATE生物不稳定的磷酸盐保护基团上存在极性功能。尽管在硫酯官能度附近掺入氨基残基的衍生物显示出低的化学稳定性，但是在SATE部分上引入一个或两个羟基基团赋予所得前药对酯酶水解的高抗性。因此，这些原核苷酸之一，即AZT 2的单羟基化SATE衍生物，能够以完整的形式穿过Caco-2细胞单层，

  DOI：

  10.1016/j.bmc.2008.06.024