2',3'-dideoxy-3'-fluoro-2-thiothymidine 5'-monophosphate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2',3'-dideoxy-3'-fluoro-2-thiothymidine 5'-monophosphate
• 英文别名: [(2R,3S,5R)-3-fluoro-5-(5-methyl-4-oxo-2-thioxo-pyrimidin-1-yl)tetrahydrofuran-2-yl]methyl dihydrogen phosphate；[(2R,3S,5R)-3-fluoro-5-(5-methyl-4-oxo-2-sulfanylidenepyrimidin-1-yl)oxolan-2-yl]methyl dihydrogen phosphate
• 化学式: C₁₀H₁₄FN₂O₆PS
• 分子量: 340.269
• InChiKey: IRIGPSWJGXABKM-XLPZGREQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  140
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2',3'-dideoxy-3'-fluoro-2-thiothymidine 5'-monophosphate 在 吡啶 作用下， 以 甲醇 为溶剂， 反应 21.5h， 生成 P1-(2',3'-dideoxy-3'-azidothymidine)-P2-(2',3'-dideoxy-3'-fluoro-2-thiothymidine)-pyrophosphate disodium salt
  参考文献：
  名称：

  Synthesis, Biological Properties and Anti-HIV-1 Activity of New Pyrimidine P₁,P₂-Dinucleotides

  摘要：

  New homo- and hetero-P1,P2-dinucleotides were prepared with the use of multistep procedures starting from the monophosphates of 3'-fluoro-2-thiothymidine, 3'-fluoro-4-thiothymidine, AZT and 1-[(2-hydroxyethoxy)-methyl-5-propyl-6-phenylselenenyl]uracil. Anti-HIV properties of the synthesized P1,P2-dinucleotides were evaluated against laboratory syncytia inducing strain HIV-1 in CEM-T4 cells. Anti-HIV activities were in the range of 5-45 nM, and therapeutic indexes were higher than 4666-14000. Interactions of the above mentioned compounds with recombinant HIV-1 reverse transcriptase were also investigated. The obtained results point to reverse transcriptase inhibition, with somewhat lower inhibitory activity than that of their parental nucleoside-5'-triphosphates. Compound 6 may be regarded as a potent anti-HIV/AIDS drug.

  DOI：

  10.1080/15257771003738642
• 作为产物：
  描述：

  1-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-2-thiothymine 在 weat shoot phosphotransferase 作用下， 生成 2',3'-dideoxy-3'-fluoro-2-thiothymidine 5'-monophosphate
  参考文献：
  名称：

  2'，3'-Dideoxy-3'-fluorothymidine的胸苷类似物及其磷酸化和膦酰基化衍生物：合成，与HIV逆转录酶的相互作用以及体外抗HIV活性

  摘要：

  寻找新的，经过修饰的20,30-二脱氧核苷，潜在的逆转录酶（RT）抑制剂，仍然特别令人感兴趣。骨髓毒性和当前使用核苷的快速发展耐药性表明需要新型RT抑制剂。20,30-Dideoxy-30-fluorothymidine（FLT）是一种嘧啶30-deoxy30-取代的胸苷类似物，是最有效的HIV体外抑制剂及其逆转录酶之一，但在体内表现出血液学毒性。先前已经表明，一些5-取代的20,30-二脱氧尿苷衍生物表现出更具选择性的抗HIV活性。在我们看来，向FLT引入取代基降低了N（3）-H的解离的pKa值，并增强了嘧啶部分的疏水性，可能会影响其抑制性能，并提高选择性。

  DOI：

  10.1081/ncn-120022698

文献信息

• Thiated Analogues of 2′,3′-Dideoxy-3′-fluorothymidine and Their Phosphorylated and Phosphonylated Derivatives: Synthesis, Interaction with HIV Reverse Transcriptase, and In Vitro Anti-HIV Activity
  作者：A. Miazga、K. Felczak、M. Bretner、M. A. Siwecka、A. Piasek、T. Kulikowski

  DOI：10.1081/ncn-120022698

  日期：2003.10

  more selective anti-HIV activity. It appeared to us that an introduction to FLT of the substituents decreasing the pKa value for dissociation of N(3)-H, and enhancing hydrophobic properties of pyrimidine moiety may affect its inhibitory properties, with improved selectivity. It was therefore of interest to synthesize and to test the activity and cytotoxicity of hydrophobic analogues of FLT, and investigate

  寻找新的，经过修饰的20,30-二脱氧核苷，潜在的逆转录酶（RT）抑制剂，仍然特别令人感兴趣。骨髓毒性和当前使用核苷的快速发展耐药性表明需要新型RT抑制剂。20,30-Dideoxy-30-fluorothymidine（FLT）是一种嘧啶30-deoxy30-取代的胸苷类似物，是最有效的HIV体外抑制剂及其逆转录酶之一，但在体内表现出血液学毒性。先前已经表明，一些5-取代的20,30-二脱氧尿苷衍生物表现出更具选择性的抗HIV活性。在我们看来，向FLT引入取代基降低了N（3）-H的解离的pKa值，并增强了嘧啶部分的疏水性，可能会影响其抑制性能，并提高选择性。
• Synthesis, Biological Properties and Anti-HIV-1 Activity of New Pyrimidine P₁,P₂-Dinucleotides
  作者：A. Miazga、P. Ziemkowski、M. A. Siwecka、A. Lipniacki、A. Piasek、T. Kulikowski

  DOI：10.1080/15257771003738642

  日期：2010.6.10

  New homo- and hetero-P1,P2-dinucleotides were prepared with the use of multistep procedures starting from the monophosphates of 3'-fluoro-2-thiothymidine, 3'-fluoro-4-thiothymidine, AZT and 1-[(2-hydroxyethoxy)-methyl-5-propyl-6-phenylselenenyl]uracil. Anti-HIV properties of the synthesized P1,P2-dinucleotides were evaluated against laboratory syncytia inducing strain HIV-1 in CEM-T4 cells. Anti-HIV activities were in the range of 5-45 nM, and therapeutic indexes were higher than 4666-14000. Interactions of the above mentioned compounds with recombinant HIV-1 reverse transcriptase were also investigated. The obtained results point to reverse transcriptase inhibition, with somewhat lower inhibitory activity than that of their parental nucleoside-5'-triphosphates. Compound 6 may be regarded as a potent anti-HIV/AIDS drug.