(E)-5-(2-bromovinyl)-2’-deoxyuridine-5’-[1-naphthyl(benzyloxy-L-alaninyl)]phosphate

• 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: (E)-5-(2-bromovinyl)-2’-deoxyuridine-5’-[1-naphthyl(benzyloxy-L-alaninyl)]phosphate
• 英文别名: CPF 98；benzyl (2S)-2-[[[(2R,3S,5R)-5-[5-[(E)-2-bromoethenyl]-2,4-dioxopyrimidin-1-yl]-3-hydroxyoxolan-2-yl]methoxy-naphthalen-1-yloxyphosphoryl]amino]propanoate
• 化学式: C₃₁H₃₁BrN₃O₉P
• 分子量: 700.48
• InChiKey: SSZYXLJZIWJPOK-JWXOQZQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  45
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  153
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  1-萘基二氯磷酸酯 在 N-甲基咪唑 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (E)-5-(2-bromovinyl)-2’-deoxyuridine-5’-[1-naphthyl(benzyloxy-L-alaninyl)]phosphate
  参考文献：
  名称：

  NAPHTHYL PHOSPHORAMIDATE DERIVATIVES OF BVdU AS POTENTIAL ANTICANCER AGENTS: DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION

  摘要：

  The phosphoramidate technology we have developed has been recently applied to BVdU, leading to NB1011 (NewBiolics Inc., California), a novel potential anticancer compound recently entered into Phase 2 of the clinical trials for colon cancer. We report in this work a new series of derivatives containing naphthol as aryl masking group on the phosphate moiety, which has shown a significant increase in anticancer activity in preliminary biological evaluations.

  DOI：

  10.1081/ncn-200061774

文献信息

• ProTides of BVdU as potential anticancer agents upon efficient intracellular delivery of their activated metabolites
  作者：Sahar Kandil、Jan Balzarini、Stephanie Rat、Andrea Brancale、Andrew D. Westwell、Christopher McGuigan

  DOI：10.1016/j.bmcl.2016.10.077

  日期：2016.12

  cancer, however their limitations in terms of cellular uptake, nucleoside kinase-mediated activation and catabolism are well-documented. The monophosphate pro-nucleotides known as ProTides represents a powerful strategy for bypassing the dependence on active transport and nucleoside kinase-mediated activation. Herein, we report the structural tuning of BVdU ProTides. Forty six phosphoramidates were

  核苷是治疗癌症的主要化疗药物，但其在细胞摄取、核苷激酶介导的激活和分解代谢方面的局限性已有充分记录。被称为 ProTides 的单磷酸前核苷酸代表了一种绕过对主动转运和核苷激酶介导的激活的依赖的强大策略。在此，我们报告了 BVdU ProTides 的结构调整。制备了 46 种氨基磷酸酯，并针对三种不同的癌细胞系进行了生物学评估；鼠白血病 (L1210)、人 CD 4 + T 淋巴细胞 (CEM) 和人宫颈癌 (HeLa)。与 BVdU 相比，针对 L1210 细胞的效力增强了 20 倍。有趣的是，与无活性的母体 BVdU 相比，许多 ProTides 对 CEM 和 HeLa 细胞表现出较低的微摩尔活性。ProTides 对非致瘤性人肺成纤维细胞培养物显示出即使有可测量的毒性，也很差。报道了四对非对映异构体混合物的分离以及它们的光谱特性、生物活性和酶活化率的比较。
• NAPHTHYL PHOSPHORAMIDATE DERIVATIVES OF BVdU AS POTENTIAL ANTICANCER AGENTS: DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION
  作者：C. Congiatu、C. McGuigan、W. G. Jiang、G. Davies、M. D. Mason

  DOI：10.1081/ncn-200061774

  日期：2005.4.1

  The phosphoramidate technology we have developed has been recently applied to BVdU, leading to NB1011 (NewBiolics Inc., California), a novel potential anticancer compound recently entered into Phase 2 of the clinical trials for colon cancer. We report in this work a new series of derivatives containing naphthol as aryl masking group on the phosphate moiety, which has shown a significant increase in anticancer activity in preliminary biological evaluations.