O-[β-D-arabinofuranosylcytosine]-O'-[S-(2,2-dimethyl-3-hydroxypropionyl)-2-thioethyl]-O''-phenylphosphate | 1192047-69-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: O-[β-D-arabinofuranosylcytosine]-O'-[S-(2,2-dimethyl-3-hydroxypropionyl)-2-thioethyl]-O''-phenylphosphate
• 英文别名: S-[2-[[(2R,3S,4S,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-phenoxyphosphoryl]oxyethyl] 3-hydroxy-2,2-dimethylpropanethioate
• CAS: 1192047-69-0
• 化学式: C₂₂H₃₀N₃O₁₀PS
• 分子量: 559.534
• InChiKey: AQYUQQUQXINNEC-MCTBDPMPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  37
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  216
• 氢给体数：
  4
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  O-[4-N,N-2',3'-O-tetra-(tert-butyloxycarbonyl)-β-D-arabinofuranosylcytosine]-O'-[S-(2,2-dimethyl-3-triphenylmethoxypropionyl)-2-thioethyl]-O''-phenylphosphate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.25h， 以55%的产率得到O-[β-D-arabinofuranosylcytosine]-O'-[S-(2,2-dimethyl-3-hydroxypropionyl)-2-thioethyl]-O''-phenylphosphate
  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