5-ethynyl-2'-deoxyuridylate | 79897-02-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: 5-ethynyl-2'-deoxyuridylate
• 英文别名: ((2R,3S,5R)-5-(5-Ethynyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3-hydroxytetrahydrofuran-2-yl)methyl dihydrogen phosphate；[(2R,3S,5R)-5-(5-ethynyl-2,4-dioxopyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methyl dihydrogen phosphate
• CAS: 79897-02-2
• 化学式: C₁₁H₁₃N₂O₈P
• 分子量: 332.207
• InChiKey: AQSXPZRJLDMJIN-DJLDLDEBSA-N

物化性质

• 密度：
  1.73±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.9
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  146
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  5-乙炔-2-脱氧尿苷 在 吡啶 、 三氯氧磷 作用下， 以 水 、 乙腈 为溶剂， 反应 4.0h， 生成 5-ethynyl-2'-deoxyuridylate
  参考文献：
  名称：

  5-乙炔基-2'-脱氧尿苷酸与胸苷酸合成酶的相互作用。

  摘要：

  已经研究了5-乙炔基-2'-脱氧尿苷酸（5-乙炔基-dUMP； 1）与胸苷酸（dTMP）合成酶的相互作用。该化合物是酶的抑制剂，当通过添加酶（Ki = 2.7 X 10（-6）M）引发反应时，可与2'-deoxyuridylate（dUMP）竞争。但是，将1与dTMP合成酶预温育后，抑制模式变为非竞争性。在1的存在下酶反应的时间过程是非线性的，表明结合随时间增加。没有发生酶的不可逆失活。该化合物似乎没有由于与酶相互作用而在结构上发生改变。dTMP合成酶，化合物1和5,10-亚甲基四氢叶酸之间形成三元复合物，

  DOI：

  10.1021/jm00144a036

文献信息

• Enzyme catalyzed therapeutic compounds
  申请人：——

  公开号：US20040077588A1

  公开（公告）日：2004-04-22

  This invention provides novel substrate compounds that selectively inhibit the proliferation f path logical cells, for example, pathological cells that endogenously overexpress a target enzyme that confers resistance to biologic and chemotherapeutic agents. The enzyme acts on a substrate compound to 1) convert it to a cellular toxin and/or 2) release a toxic byproduct. In one embodiment, the activity of the target enzyme has been greatly enhanced in a target cell as a result of loss f tum r suppressor function and/or selection resulting from previous exposure to chemotherapy. In another embodiment, the pathological cell contains a target enzyme that is an expression product of an infectious agent in the cell. Further provided by this invention is a method for treating a subject by delivering to the subject a prodrug as described herein. The prodrugs f this invention may be used alone or in combination with ther chemotherapeutics or alternative anti-cancer therapies such as radiation.

  本发明提供了新型底物化合物，其选择性地抑制病理细胞的增殖，例如，内源性过度表达靶酶的病理细胞，该靶酶赋予生物和化学治疗药物抵抗力。该酶作用于底物化合物，以1）将其转化为细胞毒素和/或2）释放有毒副产物。在一种实施例中，由于肿瘤抑制因子功能的丧失和/或先前接受化疗的选择，靶细胞中的靶酶活性已被大大增强。在另一种实施例中，病理细胞包含一个靶酶，该靶酶是细胞内感染因子的表达产物。本发明还提供了一种通过向受试者输送如本文所述的前药来治疗受试者的方法。本发明的前药可以单独使用或与其他化疗药物或替代抗癌疗法（例如放疗）联合使用。
• Synergistic ECTA compositions
  申请人：——

  公开号：US20020147175A1

  公开（公告）日：2002-10-10

  This invention provides compositions containing an effective amount of a novel substrate compound that selectively inhibit the proliferation of hyperproliferative cells, for example, pathological cells that endogenously overexpress a target enzyme that confers resistance to biologic and chemotherapeutic agents and an effective amount of a nucleoside transport antagonistic agents. Further provided by this invention is a method for treating a subject by delivering to the subject the composition as described herein. The compositions of this invention may be used alone or in combination with other chemotherapeutics or alternative anti-cancer therapies such as radiation.

  本发明提供了一种含有有效量的新型底物化合物的组合物，该化合物选择性地抑制过度增殖的细胞，例如，内源性过度表达靶酶的病理细胞，并提供了有效量的核苷酸转运拮抗剂。本发明还提供了一种通过向受试者输送所述组合物来治疗受试者的方法。本发明的组合物可以单独使用或与其他化疗药物或替代抗癌疗法（如放疗）结合使用。
• Enzyme catalyzed therapeutic agents
  申请人：Newbiotics Inc.

  公开号：EP1167972A2

  公开（公告）日：2002-01-02

  This invention provides a method for identifying potential therapeutic agents by contacting a target cell with a candidate therapeutic agent which is a selective substrate for an endogenous, intracellular enzyme in the cell which is enhanced in its expression as a result of selection by biologic or chemotherapy. This invention also provides methods and examples of molecules for selectively killing a pathological cell by contacting the cell with a prodrug that is a selective substrate for an endogenous, intracellular enzyme. The prodrug is subsequently converted to a cellular toxin. Further provided by this invention is a method for treating a pathology characterized by pathological, hyperproliferative cells in a subject by administering to the subject a prodrug that is a selective substrate for an endogenous, overexpressed, intracellular enzyme, and converted by the enzyme to a cellular toxin in the hyperproliferative cell.

  本发明提供了一种用于鉴定潜在治疗剂的方法，方法是将候选治疗剂与靶细胞接触，候选治疗剂是细胞中内源性细胞内酶的选择性底物，这种细胞内酶由于生物或化疗的选择而表达增强。本发明还提供了选择性杀死病理细胞的分子的方法和实例，方法是使细胞与一种原药接触，该原药是一种内源性细胞内酶的选择性底物。原药随后转化为细胞毒素。本发明还提供了一种治疗以病理细胞过度增殖为特征的病症的方法，该方法是向受试者施用一种原药，该原药是一种内源性、过度表达的细胞内酶的选择性底物，并在过度增殖细胞中被该酶转化为细胞毒素。
• ENZYME CATALYZED THERAPEUTIC AGENTS
  申请人：Newbiotics Inc.

  公开号：EP1045897B1

  公开（公告）日：2002-01-30
• ENZYME CATALYZED THERAPEUTIC ACTIVATION
  申请人：Celmed Oncology (USA), Inc.

  公开号：EP1200455B1

  公开（公告）日：2009-04-22