3'-Deoxy-2-O-ethyl-3'-fluorothymidine

• 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: 3'-Deoxy-2-O-ethyl-3'-fluorothymidine
• 英文别名: 1-(2,3-dideoxy-3-fluoro-beta-erythro-pentofuranosyl)-2-ethoxy-5-methylpyrimidin-4(1H)-one；2-ethoxy-1-[(2R,4S,5R)-4-fluoro-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidin-4-one
• 化学式: C₁₂H₁₇FN₂O₄
• 分子量: 272.276
• InChiKey: YWOQIQOWXKBCSL-IVZWLZJFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  71.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3'-Deoxy-2-O-ethyl-3'-fluorothymidine 在 4-二甲氨基吡啶 、 硫化氢 、 氨 、 四甲基胍 作用下， 以 吡啶 、 甲醇 为溶剂， 反应 17.0h， 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
• 作为产物：
  描述：

  1-(2,5-dideoxy-5-O-tosyl-β-D-threo-pentofuranosyl)thymine 在 二乙胺基三氟化硫 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 3'-Deoxy-2-O-ethyl-3'-fluorothymidine
  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

• Synthesis of 2-O-ethyl analogues of 3?-azido- and 3?-fluoro-2?,3?-dideoxyuridines and evaluation of their biological activity against HIV
  作者：H. M. Abdel-Bary、A. A-H Abdel-Rahman、E. B. Pedersen、C. Nielsen

  DOI：10.1007/bf00807175

  日期：——

  2-O-Ethyluracil and 2-O-ethylthymine were silylated with 1,1,1,3,3,3-hexamethyldisilazane and condensed in the presence of TMS triflate with 2,3-dideoxy-3-fluoro-D-erythro-pentofuranoside, 3-azido-2,3-dideoxy-D-erythro-pentofuranoside and 2,3-dideoxy-3-phthalimido-beta-D-erythro-pentofuranose furanose derivatives to give the corresponding 2-O-ethyl nucleosides. Deprotection with saturated methanolic ammonia afforded the 2',3'-dideoxy-3'-fluoro-2-O-ethyluridines whereas 3'-azido-2',3'-dideoxy-3-O-ethyluridine was obtained by deprotection with tetrabutylammonium fluoride in tetrahydrofuran. 3'-Amino-2',3'-dideoxy-3-O-ethyluridine could be obtained only by treatment of the corresponding 3'-azido nucleoside with triphenylphosphine in pyridine. 3'-Deoxy-2-O-ethyl-3'-fluorothymidine (6b) showed moderate activity against HIV-1.
• 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
  作者：Agnieszka Miazga、François Hamy、Séverine Louvel、Thomas Klimkait、Zofia Pietrusiewicz、Anna Kurzyńska-Kokorniak、Marek Figlerowicz、Patrycja Wińska、Tadeusz Kulikowski

  DOI：10.1016/j.antiviral.2011.05.012

  日期：2011.10

  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.

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