1-(3-azido-2,3-dideoxy-β-D-erythro-pentofuranosyl)-5-fluorouracil | 87190-74-7

• 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: 1-(3-azido-2,3-dideoxy-β-D-erythro-pentofuranosyl)-5-fluorouracil
• 英文别名: 3'-azido-2',3'-dideoxy-5-fluorouridine；3'-azido-5-fluoro-2',3'-dideoxyuridine；AddFU；1-[(2R,4S,5S)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-fluoropyrimidine-2,4-dione
• CAS: 87190-74-7
• 化学式: C₉H₁₀FN₅O₄
• 分子量: 271.208
• InChiKey: YXDSILBXLUFJID-RRKCRQDMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  93.2
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(3-azido-2,3-dideoxy-β-D-erythro-pentofuranosyl)-5-fluorouracil 在 吡啶 、 4-氯苯基二氯磷酸酯 作用下， 反应 72.0h， 生成 Acetic acid (2S,3S,5R)-3-azido-5-(5-fluoro-2-oxo-4-[1,2,4]triazol-1-yl-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethyl ester
  参考文献：
  名称：

  Synthesis and biological activity of various 3'-azido and 3'-amino analogs of 5-substituted pyrimidine deoxyribonucleosides

  摘要：

  Various new 5-substituted 3'-azido- and 3'-amino derivatives of 2'-deoxyuridine and 2'-deoxycytidine have been synthesized and biologically evaluated. Among these compounds, 3'-amino-2',3'-dideoxy-5-fluorouridine (3), 3'-amino-2',3'-dideoxycytidine (7a), and 3'-amino-2',3'-dideoxy-5-fluorocytidine (7c) were found to be the most active against murine L1210 and sarcoma 180 neoplastic cells in vitro, with an ED50 of 15 and 1 microM, 0.7 and 4 microM, and 10 and 1 microM, respectively. The 3'-azido derivatives, 2 and 6c, were less active in comparison with their 3'-amino counterparts. In addition, the 5-fluoro-3'-amino nucleosides, 3 and 7c, were tested against L1210 leukemia bearing CDF1 mice. Our preliminary findings indicate that compound 7c (6 X 200 mg/kg) was as active as the positive control, 5-fluorouracil (6 X 20 mg/kg), yielding a T/C X 100 of 146 and 129, respectively. However, 3 was found to be inactive in this experiment.

  DOI：

  10.1021/jm00366a006
• 作为产物：
  描述：

  5-氟-2'-脱氧脲核苷 在 六甲基磷酰三胺 、 叠氮化锂 、 偶氮二甲酸二异丙酯 、 氨 、 对甲苯磺酸 、 三苯基膦 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.75h， 生成 1-(3-azido-2,3-dideoxy-β-D-erythro-pentofuranosyl)-5-fluorouracil
  参考文献：
  名称：

  3'-叠氮基-2'，3'-二脱氧-5-氟尿苷氨基磷酸酯的合成及其抗癌活性的评价

  摘要：

  一系列新颖的4-氯苯基的Ñ的3'-叠氮基2 -烷基氨基磷酸酯'，3'-二脱氧-5-氟尿苷（12 - 21）由3'-叠氮基-2的磷酸化的方法合成'，3' -二脱氧-5-氟尿嘧啶（4）与4-氯苯基二三唑啉（10），然后与适当的胺反应。合成氨基磷酸酯（12 - 21使用磺酰罗丹明B（SRB）测定子宫颈（HeLa细胞），口服（KB）和乳癌（MCF-7）：）在三种人癌细胞系对它们的细胞毒活性进行评价。在所有研究的癌细胞中，最高的活性是由氨基磷酸亚胺13与N一起显示的。-乙基取代基及其活性远高于母体核苷。在所有使用的细胞系中，具有N-炔丙基取代基的氨基磷酸酯17也表现出良好的活性。

  DOI：

  10.1016/j.ejmech.2013.06.047

文献信息

• Nucleoside dimers analogs containing floxuridine and thymidine with unnatural linker groups: synthesis and cancer line studies. Part III
  作者：Dagmara Baraniak、Piotr Ruszkowski、Daniel Baranowski、Grzegorz Framski、Jerzy Boryski

  DOI：10.1080/15257770.2019.1641206

  日期：2019.12.2

  Abstract Two series of novel fluorinated nucleosides dimers with an unnatural 1,2,3-triazole linkage were synthesized. The obtained molecules were prepared using “click” chemistry approach based on copper(I) catalyzed Huisgen azide–alkyne cycloaddition. It was performed between 3′- and 5′-azido-nucleosides as the azide components, and the 3′-O- and 5′-O-propargyl-nucleosides as the alkyne components

  摘要 合成了两个系列具有非天然1,2,3-三唑键的新型氟化核苷二聚体。获得的分子是使用基于铜（I）催化的 Huisgen 叠氮化物-炔烃环加成反应的“点击”化学方法制备的。它在作为叠氮化物组分的 3'-和 5'-叠氮基核苷和作为炔组分的 3'-O-和 5'-O-炔丙基核苷之间进行。基于对 3JHH、3JH1'C2 和 3JH1'C6 的分析，我们估计了糖部分的构象偏好和围绕糖苷键的方向。所有描述的核苷二聚体类似物都通过光谱方法表征，并评估了它们在三种人类癌细胞系中的体外细胞毒性：宫颈 (HeLa)、口腔 (KB) 和乳腺 (MCF-7)。
• Novel fluorophosphonate nucleotide derivatives
  申请人：MERRELL DOW PHARMACEUTICALS INC.

  公开号：EP0339161A1

  公开（公告）日：1989-11-02

  This invention relates to fluoromethylphosphonate derivatives of certain nucleosides, to methods for their preparation and to their use as antiviral and antitumoral agents.

  这项发明涉及某些核苷类化合物的氟甲基磷酸酯衍生物，涉及它们的制备方法以及它们作为抗病毒和抗肿瘤药物的用途。
• Antineoplastic activity of 3'-(chloroethyl)nitrosourea analogs of 2'-deoxyuridine and 2'-deoxy-5-fluorouridine
  作者：Tai Shun Lin、William F. Brubaker、Zi Hou Wang、Susanna Park、William H. Prusoff

  DOI：10.1021/jm00155a044

  日期：1986.5

  The (chloroethyl)nitrosourea analogues of 2'-deoxyuridine and 2'-deoxy-5-fluorouridine, 3'-[3-(2-chloroethyl)-3-nitrosoureido]-2',3'-dideoxyuridine (3'-CdUNU, 7) and 3'-[3-(2-chloroethyl)-3-nitrosoureido]-2,3'-dideoxy-5-fluorouridine (3'-CFdUNU, 8), have been synthesized by treatment of the corresponding 3'-amino nucleosides with chloroethyl isocyanate, followed by nitrosation of the resulting ureas

  2'-脱氧尿苷和2'-脱氧-5-氟尿苷，3'-[3-（2-氯乙基）-3-亚硝基脲基] -2'，3'-二脱氧尿苷（3'-CdUNU）的（氯乙基）亚硝基脲类似物，7）和3'-[3-（2-氯乙基）-3-亚硝基脲基] -2,3'-二脱氧-5-氟尿苷（3'-CFdUNU，8），通过处理相应的3' -氨基核苷与氯乙基异氰酸酯，然后亚硝化所得的脲。核苷亚硝基脲7和8在荷瘤小鼠中对L1210白血病表现出显着的抗癌活性。在40 mg / kg的最佳剂量水平下，7和8分别产生90％和60％的“治愈”（大于60天存活者）。讨论了构效关系。
• [EN] 2',3'-DIDEOXY-5-FLUOROURIDINE DERIVATIVES, A PROCESS FOR THE MANUFACTURE THEREOF AND APPLICATION THEREOF<br/>[FR] DÉRIVÉS DE 2',3'-DIDÉSOXY-5-FLUOROURIDINE, UN PROCÉDÉ DE FABRICATION DE CEUX-CI ET LEUR APPLICATION
  申请人：UNIV ADAM MICKIEWICZ

  公开号：WO2015050467A1

  公开（公告）日：2015-04-09

  The subject matter of the invention is novel 2',3'-dideoxy-5-fluorouridine derivatives of general formula 1. wherein: R1 denotes cinchona alkaloid fragment with defined absolute configuration at C-8 and C-9 atoms. In the second aspect, the subject matter of the invention is a process for the manufacture of 2',3'-dideoxy-5-fluorouridine derivatives of general formula 1. In the third aspect, the subject matter of the invention is an application of 2',3'-dideoxy-5-fluorouridine derivatives of general formula1 of the invention in the anticancer treatment of breast cancer, cervical cancer and hepatic cancer.

  该发明的主题是一种新颖的通式1中的新2',3'-二脱氧-5-氟尿苷衍生物，其中：R1表示奎宁生物碱片段，在C-8和C-9原子处具有定义的绝对构型。在第二方面，该发明的主题是制造通式1中的2',3'-二脱氧-5-氟尿苷衍生物的方法。在第三方面，该发明的主题是将该发明的通式1中的2',3'-二脱氧-5-氟尿苷衍生物应用于乳腺癌、宫颈癌和肝癌的抗癌治疗。
• Nucleoside dimers analogues with a 1,2,3-triazole linkage: conjugation of floxuridine and thymidine provides novel tools for cancer treatment. Part II
  作者：Dagmara Baraniak、Daniel Baranowski、Piotr Ruszkowski、Jerzy Boryski

  DOI：10.1080/15257770.2019.1610891

  日期：2019.11.2

  Abstract The fluorinated nucleoside dimers with a 1,2,3-triazole linkage are novel compounds within the field of bioorganic chemistry. We report on the synthesis and properties of two groups of nucleoside dimers analogs possessing a different arrangement of the 1,4-disubstituted 1,2,3-triazole linkage. Based on analysis of the 3JHH, 3JH1′C2, and 3JH1′C6 we estimated conformational preferences of sugar

  摘要具有1,2,3-三唑键的氟化核苷二聚体是生物有机化学领域中的新型化合物。我们报告了具有1,4-二取代的1,2,3-三唑键的不同排列的两组核苷二聚体类似物的合成和性质。基于对3JHH，3JH1'C2和3JH1'C6的分析，我们估计了糖部分的构象偏爱和糖苷键周围的方向。这些化合物显示出中等的抗癌活性，并在三种不同的癌细胞系中进行了细胞抑制研究。