5-fluoro-2'-deoxyuridine-5'-O-[phenyl(benzoxy-L-alaninyl)]phosphate | 1338052-09-7

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 5-fluoro-2'-deoxyuridine-5'-O-[phenyl(benzoxy-L-alaninyl)]phosphate
• 英文别名: CPF381；5-fluoro-2'-deoxyuridine-5'-O-[phenyl(benzoxy-L-alaninyl)] phosphate；benzyl (2S)-2-[[[(2R,3S,5R)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate
• CAS: 1338052-09-7
• 化学式: C₂₅H₂₇FN₃O₉P
• 分子量: 563.476
• InChiKey: ALBAUCOZFCGPKT-QFZJFBSESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  39
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  153
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  phenyl(benzyloxy-L-alaninyl)phosphorochloridate 、 5-氟-2'-脱氧脲核苷 在 叔丁基氯化镁 作用下， 以 四氢呋喃 为溶剂， 以8%的产率得到5-fluoro-2'-deoxyuridine-5'-O-[phenyl(benzoxy-L-alaninyl)]phosphate
  参考文献：
  名称：

  PHOSPHORAMIDATE DERIVATIVES OF 5 - FLUORO - 2` - DEOXYURIDINE FOR USE IN THE TREATMENT OF CANCER

  摘要：

  本发明公开了用于治疗癌症的5-氟-2'-脱氧尿嘧啶的磷酰胺衍生物，特别是用于治疗患有耐药性的癌症的情况，例如，在患有核苷转运蛋白水平降低的细胞、核苷激酶缺陷细胞、支原体感染细胞或胸苷酸合成酶水平升高的细胞的患者中。

  公开号：

  US20140057866A1

文献信息

• [EN] PHOSPHORAMIDATE DERIVATIVES OF 5 - FLUORO - 2 ' - DEOXYURIDINE FOR USE IN THE TREATMENT OF CANCER<br/>[FR] DÉRIVÉS PHOSPHORAMIDATES DE 5-FLUORO-2'- DÉSOXYURIDINE DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT D'UN CANCER
  申请人：NUCANA BIOMED LTD

  公开号：WO2012117246A1

  公开（公告）日：2012-09-07

  Phosphoramidate derivatives of 5-fluoro-2'-deoxyuridine are disclosed for use in the treatment of cancer, especially in the treatment of cancer where the patient shows resistance, for example, in a patient with cells with a lowered level of nucleoside transporter proteins and/or with nucleoside kinase-deficient cells and/or with mycoplasma-infected cells and/or with cells with a raised level of thymidylate synthase.

  5-氟-2'-脱氧尿苷的磷酰胺酸衍生物被揭示用于治疗癌症，特别是在治疗患者出现抗药性的情况下，例如，在具有降低核苷转运蛋白水平和/或核苷激酶缺陷细胞和/或受到支原体感染细胞和/或具有升高脱氧胸苷酸合成酶水平的细胞的患者。
• Phosphoramidate ProTides of the Anticancer Agent FUDR Successfully Deliver the Preformed Bioactive Monophosphate in Cells and Confer Advantage over the Parent Nucleoside
  作者：Christopher McGuigan、Paola Murziani、Magdalena Slusarczyk、Blanka Gonczy、Johan Vande Voorde、Sandra Liekens、Jan Balzarini

  DOI：10.1021/jm200815w

  日期：2011.10.27

  The fluorinated pyrimidine family of nucleosides continues to represent major current chemotherapeutic agents for treating solid tumors. We herein report their phosphate prodrugs, ProTides, as promising new derivatives, which partially bypass the dependence of the current drugs on active transport and nucleoside kinase-mediated activation. They are also resistant to metabolic deactivation by phosphorolytic enzymes. We report 39 ProTides of the fluorinated pyrimidine FUDR with variation in the aryl, ester, and amino acid. regions. Notably, only certain ProTide motifs are successful in delivering the nucleoside monophosphate into intact cells. We also find that the ProTides retain activity in mycoplasma infected cells, unlike FUDR. Data suggest these compounds to be worthy of further progression.