naphthalene-1-yl-L-phenylalanine benzyloxy ester phosphorochloridate | 874362-24-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: naphthalene-1-yl-L-phenylalanine benzyloxy ester phosphorochloridate
• 英文别名: 1-naphthyl (benzyloxy-L-phenylalaninyl)phosphorochloridate；1-naphthyl(benzoxy-L-phenylalaninyl)phosphorochloridate；1-naphthyl-(benzoxy-L-phenylalaninyl)phosphochloridate；benzyl (2S)-2-[[chloro(naphthalen-1-yloxy)phosphoryl]amino]-3-phenylpropanoate
• CAS: 874362-24-0
• 化学式: C₂₆H₂₃ClNO₄P
• 分子量: 479.9
• InChiKey: MDEYNHPSVWCGJZ-PPVAYSNCSA-N

物化性质

• 沸点：
  628.2±65.0 °C(Predicted)
• 密度：
  1.308±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  naphthalene-1-yl-L-phenylalanine benzyloxy ester phosphorochloridate 、 5-氟-2'-脱氧脲核苷 在 N-甲基咪唑 作用下， 以 四氢呋喃 为溶剂， 以1%的产率得到5-fluoro-2'-deoxyuridine-5'-O-[1-naphthyl(benzoxy-L-phenylalaninyl)]phosphate
  参考文献：
  名称：

  Phosphoramidate ProTides of the Anticancer Agent FUDR Successfully Deliver the Preformed Bioactive Monophosphate in Cells and Confer Advantage over the Parent Nucleoside

  摘要：

  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.

  DOI：

  10.1021/jm200815w
• 作为产物：
  描述：

  1-萘基二氯磷酸酯 、 3-苯基-L-丙氨酸苄酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 naphthalene-1-yl-L-phenylalanine benzyloxy ester phosphorochloridate
  参考文献：
  名称：

  Novel Potential Anticancer Naphthyl Phosphoramidates of BVdU:  Separation of Diastereoisomers and Assignment of the Absolute Configuration of the Phosphorus Center

  摘要：

  We have previously reported our SAR optimization of the anticancer agent thymectacin. Tuning of the parent ProTide structure initially involved the amino acid and, subsequently, the aromatic masking group on the phosphate moiety. Herein, derivatives bearing the combined modifications are reported and biological evaluation is described. Moreover, separation of the diastereoisomeric final product mixture shows a different cytostatic activity for the two diastereoisomers. Through computational and NMR studies, the absolute stereochemistry of the phosphorus center of the two diastereoisomers has been suggested.

  DOI：

  10.1021/jm0509896

文献信息

• [EN] ADENOSINE DERIVATIVES FOR USE IN THE TREATMENT OF CANCER<br/>[FR] DÉRIVÉS DE L'ADÉNOSINE UTILISABLES DANS LE TRAITEMENT DU CANCER
  申请人：NUCANA BIOMED LTD

  公开号：WO2017207989A1

  公开（公告）日：2017-12-07

  The present invention relates to chemical compounds of formula (I) as defined in the amended claims, their preparation and their use in the treatment of cancer.

  本发明涉及化学式（I）所定义的化合物，其制备以及在癌症治疗中的应用。
• Application of the phosphoramidate ProTide approach to the antiviral drug ribavirin
  作者：Marco Derudas、Andrea Brancale、Lieve Naesens、Johan Neyts、Jan Balzarini、Christopher McGuigan

  DOI：10.1016/j.bmc.2010.02.015

  日期：2010.4

  Ribavirin is a nucleoside analogue with broad antiviral activity. Here we report the synthesis and biological evaluation of novel ribavirin ProTides designed to deliver the bioactive ribavirin monophosphate into cells. Some of the compounds display activity similar to the parent nucleoside against a range of viruses. Enzymatic, cell lysate and preliminary modeling studies have been performed to investigate

  利巴韦林是具有广泛抗病毒活性的核苷类似物。在这里，我们报告了旨在将生物活性的利巴韦林单磷酸酯传递到细胞中的新型利巴韦林ProTides的合成和生物学评估。一些化合物显示出与母体核苷相似的针对多种病毒的活性。已经进行了酶促，细胞裂解物和初步模型研究，以研究ProTides缺乏增强效力的方法，这些研究表明ProTide激活过程的最终氨基酸裂解步骤失败，导致单磷酸核苷的释放效率低下。
• Novel Potential Anticancer Naphthyl Phosphoramidates of BVdU:  Separation of Diastereoisomers and Assignment of the Absolute Configuration of the Phosphorus Center
  作者：Costantino Congiatu、Andrea Brancale、Malcolm D. Mason、Wen G. Jiang、Christopher McGuigan

  DOI：10.1021/jm0509896

  日期：2006.1.1

  We have previously reported our SAR optimization of the anticancer agent thymectacin. Tuning of the parent ProTide structure initially involved the amino acid and, subsequently, the aromatic masking group on the phosphate moiety. Herein, derivatives bearing the combined modifications are reported and biological evaluation is described. Moreover, separation of the diastereoisomeric final product mixture shows a different cytostatic activity for the two diastereoisomers. Through computational and NMR studies, the absolute stereochemistry of the phosphorus center of the two diastereoisomers has been suggested.
• 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.