(E)-5-(2-bromovinyl)-2'-deoxyuridine 5'-monophosphate | 80860-82-8

• 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: (E)-5-(2-bromovinyl)-2'-deoxyuridine 5'-monophosphate
• 英文别名: (E)-5-(2-bromovinyl)-2'-deoxyuridine monophosphate；5-(2-bromovinyl)-2'-deoxyuridine-5-monophosphate；BVDU-MP；Brivudine monophosphate；[(2R,3S,5R)-5-[5-[(E)-2-bromoethenyl]-2,4-dioxopyrimidin-1-yl]-3-hydroxyoxolan-2-yl]methyl dihydrogen phosphate
• CAS: 80860-82-8
• 化学式: C₁₁H₁₄BrN₂O₈P
• 分子量: 413.119
• InChiKey: LKWCVKAHHUJPQO-PIXDULNESA-N

物化性质

• 密度：
  1.992±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.1
• 重原子数：
  23
• 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

• 作为反应物：
  描述：

  N,N'-羰基二咪唑 、 (E)-5-(2-bromovinyl)-2'-deoxyuridine 5'-monophosphate 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  Synthesis and Antitumor Activity of a Heterodinucleotide of BVDU and Gemcitabine

  摘要：

  A heterodinucleotide comprising BVDU and Gemcitabine bound together by a 5',5'-pyrophospate bridge (BVDUp(2)dFdC) has been synthesized and evaluated as antitumor agent against AH13 rat sarcoma cells. BVDUp(2)dFdC showed a cytotoxicity similar to that of Gemcitabine.

  DOI：

  10.1080/15257770802088787
• 作为产物：
  描述：

  溴夫定 在 叔丁基过氧化氢 、 phosphate buffer 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.2h， 生成 (E)-5-(2-bromovinyl)-2'-deoxyuridine 5'-monophosphate
  参考文献：
  名称：

  SYNTHESIS, HYDROLYSIS AND ANTI-EBV ACTIVITY OF A SERIES OF 3′-MODIFIEDcycloSal-BVDUMP PRONUCLEOTIDES

  摘要：

  A series of cycloSal-BVDUMP phosphate triesters has been prepared. The prototype compound was 3-methyl-cycloSal-BVDUMP 2. Furthermore, a series of 3'-O-acyl-modified derivatives having carboxylic acids with different lipophilicity or a L-configurated alpha -amino acid (phenylalanine) was prepared. The hydrolysis properties in phosphate buffer PBS as well as in PBS containing pig liver esterase (PLE) will be described. Finally, the biological activity against EBV has been determined.

  DOI：

  10.1081/ncn-100002301

文献信息

• Mutation of Gln125 to Asn Selectively Abolishes the Thymidylate Kinase Activity of Herpes Simplex Virus Type 1 Thymidine Kinase
  作者：Bart Degrève、Robert Esnouf、Erik De Clercq、Jan Balzarini

  DOI：10.1124/mol.59.2.285

  日期：2001.2.1

  contrast with wild-type HSV-1 TK, which displays both thymidine kinase and thymidylate kinase activities, the HSV-1 TK(Q125N) mutant was unable to phosphorylate pyrimidine nucleoside monophosphates but retained significant phosphorylation activity for thymidine and a series of antiherpetic pyrimidine and purine nucleoside analogs. The abrogation of HSV-1 TK-associated thymidylate kinase activity resulted

  单纯疱疹病毒1型（HSV-1）胸苷激酶（TK）具有广泛的底物特异性，为选择性抗疱疹治疗以及最近的自杀基因治疗提供了基础。现在，我们已经构建了HSV-1 TK突变酶，其中天冬酰胺（N）残基在位置125处取代了谷氨酰胺（Q），并评估了此氨基酸变化对酶活性的影响。与同时显示胸苷激酶和胸苷酸激酶活性的野生型HSV-1 TK形成鲜明对比的是，HSV-1 TK（Q125N）突变体无法磷酸化嘧啶核苷单磷酸，但对胸苷和一系列抗疱疹药具有显着的磷酸化活性。嘧啶和嘌呤核苷类似物。废除HSV-1 TK相关的胸苷酸激酶活性导致（E）-5-（2-溴乙烯基）-2'-脱氧尿苷（BVDU）的单磷酸盐形式在转染了HSV的骨肉瘤细胞中累积100倍-1 TK（Q125N）基因与表达野生型HSV-1 TK的骨肉瘤细胞相比。与野生型HSV-1 TK基因转染的骨肉瘤肿瘤细胞相比，BVDU单磷酸积累在HSV-1 TK（Q125N）基因
• 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。
• Novel phosphoramidate compounds and methods of use
  申请人：——

  公开号：US20030109697A1

  公开（公告）日：2003-06-12

  This invention provides compounds, compositions and methods for treating cancer, infectious disease, an autoimmune disorder or an inflammatory condition. Therapeutic compounds useful in the methods of this invention are 5′-phosphoramidatyl, 1,5-substituted pyrimidine compounds, derivatives, analogs and pharmaceutically acceptable salts thereof

  该发明提供了用于治疗癌症、传染病、自身免疫性疾病或炎症状况的化合物、组合物和方法。该发明方法中有用的治疗化合物是5'-磷酰胺基、1,5-取代嘧啶化合物、衍生物、类似物和药学上可接受的盐。
• 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。
• Methods to treat autoimmune and inflammatory conditions
  申请人：——

  公开号：US20020151519A1

  公开（公告）日：2002-10-17

  This invention provides methods for treating inflammatory or autoimmune diseases by contacting the affected cell or tissue with a therapeutic compound as described herein. Such pathologies include, but are not limited to rheumatoid arthritis, systemic lupus erythmatosus, psoriatic arthritis, reactive arthritis, Crohn's disease, ulcerative colitis and scleroderma. Therapeutic compounds useful in the methods of this invention are selected from the group consisting of a 1,5-substituted pyrimidine derivative or analog and substituted furano-pyrimidone analog.

  这项发明提供了一种通过使用本发明所述的治疗化合物与受影响的细胞或组织接触来治疗炎症性或自身免疫性疾病的方法。这些病理包括但不限于类风湿性关节炎、系统性红斑狼疮、银屑病性关节炎、反应性关节炎、克罗恩病、溃疡性结肠炎和硬化症。本发明方法中有用的治疗化合物选自1,5-取代嘧啶衍生物或类似物和取代呋喃嘧啶酮类似物组成的群体。