1-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-2-thiothymine | 169203-45-6

• 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-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-2-thiothymine
• 英文别名: 2',3'-dideoxy-3'-fluoro-2-thiothymidine；3'-deoxy-3'-fluoro-2-thiothymidine；S2FLT；1-(2',3'-dideoxy-3'-fluoro-β-D-ribofuranosyl)-2-thiothymine；1-(2,3-dideoxy-3-fluoro-β-D-ribofuranosyl)-2-thiothymine；1-[(2R,4S,5R)-4-fluoro-5-(hydroxymethyl)tetrahydrofuran-2-yl]-5-methyl-2-thioxo-pyrimidin-4-one；1-[(2R,4S,5R)-4-fluoro-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-2-sulfanylidenepyrimidin-4-one
• CAS: 169203-45-6
• 化学式: C₁₀H₁₃FN₂O₃S
• 分子量: 260.289
• InChiKey: FTAGYCOPYIJZGF-XLPZGREQSA-N

物化性质

• 密度：
  1.47±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  93.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-2-thiothymine 在 乙酸酐 作用下， 以 吡啶 、 氯仿 为溶剂， 生成 1-(5-O-acetyl-2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-2-thiothymine
  参考文献：
  名称：

  2',3'-dideoxynucleoside pyrimidine compounds and carbocyclic analogs

  摘要：

  本发明揭示了具有抗病毒活性的2'，3'-二去氧核苷嘧啶化合物和2-硫代胸腺嘧啶环烷衍生物。这些化合物预计会表现出与2'，3'-二去氧核苷化合物及其类似物所认可的抗病毒活性相同的效果。

  公开号：

  US05496935A1
• 作为产物：
  描述：

  1-(2,5-dideoxy-5-O-tosyl-β-D-threo-pentofuranosyl)thymine 在 4-二甲氨基吡啶 、 二乙胺基三氟化硫 、 硫化氢 、 氨 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 四甲基胍 作用下， 以 吡啶 、 甲醇 、 二氯甲烷 为溶剂， 反应 21.0h， 生成 1-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-2-thiothymine
  参考文献：
  名称：

  Thiated derivatives of 2′,3′-dideoxy-3′-fluorothymidine: Synthesis, in vitro anti-HIV-1 activity and interaction with recombinant drug resistant HIV-1 reverse transcriptase forms

  摘要：

  Various thiated analogues of thymine 2',3'-dideoxy-3'-fluoronucleoside (FLT) and their 5'-monophosphates and 5'-triphosphates were prepared with the use of modified multistep procedures. The thiated analogues of FLT and FLTMP were evaluated against the wild type and drug- and multidrug-resistant strains of HIV-1, using the replicative phenotyping format of the deCIPhR assay, and showed potent inhibition of drug-resistant HIV-1 strains at low cytotoxicity. Additionally, inhibition of recombinant drug resistant forms of reverse transcriptase from single and multiple HIV-1 mutants by the synthesized 5'-triphosphates was investigated. The strongest inhibition was observed for K103N and Delta 67 mutants and the most potent anti-HIV-1 activity against drug resistant strains and the lowest cytotoxicity was exerted by S(4)FLTMP and FLTMP which may be regarded as potential anti-HIV/AIDS agents. (C) 2011 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.antiviral.2011.05.012

文献信息

• 5′-O-Ester Prodrugs of Potent and Selective Anti-HIV Agent—2′,3′-Dideoxy-3′-fluoro-2-thiothymidine (S²FLT): Synthesis and Anti-HIV Activity
  作者：A. Miazga、N. E. Poopeiko#、A. Piasek、M. A. Siweckar、T. Kulikowski

  DOI：10.1081/ncn-120022639

  日期：2003.10

  Abstract Novel synthesis of 2′,3′-dideoxy-3′-fluoro-2-thiothymidine (SFLT) based on transformation of appropriately protected 1-β-D-threo-ribofuranosylthymine is presented. The synthesis and evaluation of SFLT 5′-O-ester prodrugs enzymatic hydrolysis, as well as their anti-HIV activity, is also described.

  摘要提出了基于适当保护的1-β-D-苏-核呋喃呋喃基胸腺嘧啶的转化，合成2'，3'-二脱氧-3'-氟-2-硫代胸腺嘧啶（SFLT）的新方法。还描述了SFLT 5'-O-酯前药酶促水解的合成和评估，以及它们的抗HIV活性。
• 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.
• Synthesis, Solution Conformation and Biological properties of 2',3'-Dideoxy-3'-fluoro-D-erythro-pentofuranosides of 2-Thiouracil and 2-Thiothymine
  作者：N. E. Poopeiko、J. Poznanski、A. Drabikowska、J. Balzarini、E. De Clercq、I. A. Mikhailopulo、D. Shugar、T. Kulikowski

  DOI：10.1080/15257779508012402

  日期：1995.5.1

  The synthesis of the alpha- and beta-anomers of 2',3'-dideoxy-3'-fluoro-2-thiouridine and 2',3'-dideoxy-3'-fluoro-2-thiothymidine via Lewis acid catalysed nucleoside condensation is described. High resolution H-1 NMR data, solution conformations and biological properties are also presented.
• Analogs of 2',3'-dideoxy-3'-fluorothymidine 5'-monophosphate (FLTMP) for use in the treatment of infections caused by human HIV-1 strains
  申请人：Instytut Biochemii i Biofizyki PAN

  公开号：EP2402357B1

  公开（公告）日：2015-10-14