5'-O-Acetyl-3'-desoxy-3'-fluor-thymidin | 51247-07-5

• 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: 5'-O-Acetyl-3'-desoxy-3'-fluor-thymidin
• 英文别名: 5'-O-acetyl-3'-deoxy-3'-fluorothymidine；3'-Fluoro-3'-deoxythymidine acetate；5'-O-acetyl-FLT；O^5'-acetyl-3'-fluoro-3'-deoxy-thymidine；1-(5-O-acetyl-3-fluoro-2,3-dideoxy-β-D-erythro-pentofuranosyl)thymine；Thymidine, 3'-deoxy-3'-fluoro-, 5'-acetate；[(2R,3S,5R)-3-fluoro-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl acetate
• CAS: 51247-07-5
• 化学式: C₁₂H₁₅FN₂O₅
• 分子量: 286.26
• InChiKey: YHHMPZAORRCRSI-IVZWLZJFSA-N

物化性质

• 熔点：
  144-146 °C
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  84.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5'-O-Acetyl-3'-desoxy-3'-fluor-thymidin 在 sodium methylate 作用下， 以 甲醇 为溶剂， 以85%的产率得到3’-脱氧-3-氟胸苷
  参考文献：
  名称：

  An efficient synthesis of 3′-fluoro-3′-deoxythymidene (FLT)

  摘要：

  A synthetic route which permits the regioselective introduction of fluoride into an FLT precursor under mild conditions and the subsequent conversion of that intermediate into FLT is reported.

  DOI：

  10.1016/s0040-4039(00)60841-9
• 作为产物：
  描述：

  5-甲磺化-2,3`-脱水胸苷 在 aluminum(III) fluoride 、 氢氟酸 、 potassium acetate 作用下， 以 1,4-二氧六环 为溶剂， 反应 7.5h， 生成 5'-O-Acetyl-3'-desoxy-3'-fluor-thymidin
  参考文献：
  名称：

  潜在的抗HIV-1核苷的氟化糖类似物。

  摘要：

  为了获得具有优于AZT，FLT或D4T的治疗指数的药物，合成了抗HIV-1核苷的几种类似物。这些包括2'，3'-dideoxy-2'，3'-difluoro-5-methyluridine（13），其阿拉伯糖类似物19，arab-5--5-甲基胞嘧啶类似物21、3'-脱氧2'，3'-二氢-2'-氟胸苷（25），3'-叠氮基2'，3'-二脱氧基2'-氟-5-甲基尿苷（29），2'-叠氮基3'-氟-2'，3'-双脱氧-5-甲基尿苷（31）和2'3'-二脱氧-2'-氟-5-甲基尿苷（37）。对这些新核苷在体外针对HIV和猫TLV的活性进行了筛选。没有一种化合物显示出明显的活性。有趣的是，活性抗HIV核苷的糖部分有这么小的修饰（即

  DOI：

  10.1021/jm00109a017

文献信息

• The Potential of Aspirin in Prodrug Synthesis: A New Potential Delivery System of AZT and FLT
  作者：Magdy A. Zahran、Lajos Kovács、Ibrahim El Sakka、Erik B. Pedersen、Claus Nielsen

  DOI：10.1002/ardp.19963290809

  日期：——

  Aspirin (O‐acetylsalicylic acid) has been used to synthesize prodrugs of 3′‐azido‐3′‐deoxythymidine (AZT) and 3′‐deoxy‐3′‐fluorothymidine (FLT). The mixed anhydride between aspirin and trifluoroacetic acid was synthesized and reacted with AZT and FLT to give the blocked nucleosides attached through the 5′‐O position to the 2‐position of 2‐methyl‐4H‐1,3‐benzodioxin‐4‐one. The prodrugs showed the same

  阿司匹林（O-乙酰水杨酸）已被用于合成3'-叠氮基-3'-脱氧胸苷（AZT）和3'-脱氧-3'-氟胸苷（FLT）的前药。阿司匹林和三氟乙酸的混合酸酐合成并与AZT和FLT反应得到通过5′-O位连接到2-甲基-4H-1,3-苯并二恶英-4-位的封闭核苷. 前药在 MT-4 细胞中显示出与原始药物相同的抗 HIV-1 活性。用于抗 HIV 研究的合成前药在生长培养基中水解，导致形成 5-O 乙酰化药物，随后将其水解为原始药物。
• Fluorinated nucleosides and process for treating retrovirus infections
  申请人：——

  公开号：US05153180A1

  公开（公告）日：1992-10-06

  A process for treating AIDS, which comprises administering to a patient in need therefor a pharmaceutical composition comprising a therapeutically effective amount of a compound having the formula ##STR1## wherein: R.sub.1 is an adenine, cytosine, guanine, thymidine, uracil, 5-substituted uracil, 5-substituted cytosine derivative, 2-fluoroadenine, 2.6-diaminopurine, 2-aminopurine, 6-thioguanine, or 7-deazaadenine group; R.sub.2 is H, or a OH group; R.sub.3 is a OH, O-acyl, O-palmitoyl group or phosphates (as free acid, or its alkali, ammonium or alkyl ammonium salts), or any other precursor group for the hydroxyl group; or a physiologically acceptable salt thereof. Furthermore, the present invention comprises the new compounds: 2',3'-dideoxy-3'-fluoro-2-fluoroadenosine, 2',3'-dideoxy-3'-fluoro-6-thioguanosine, 2',3'-dideoxy-3'-fluoro-2,6-diaminopurineriboside, 2',3'-dideoxy-3'-fluoro-2-aminopurineriboside, 2',3'-dideoxy-3'-fluoro-5-aminomethyluridine, 2',3'-dideoxy-3'-fluoro-5-azidomethyluridine, and 2',3'-dideoxy-3'-fluoro-5-hydroxymethyluridine.

  一种治疗艾滋病的方法，包括向需要该方法的患者给予含有以下化合物的药物组合物：##STR1## 其中：R.sub.1是腺嘌呤、胞嘧啶、鸟嘌呤、胸腺嘧啶、尿嘧啶、5-取代尿嘧啶、5-取代胞嘧啶衍生物、2-氟腺嘌呤、2,6-二氨基嘌呤、2-氨基嘌呤、6-硫代鸟嘌呤或7-去氮腺嘌呤基团；R.sub.2是氢或OH基团；R.sub.3是OH、O-酰基、O-棕榈酰基或磷酸盐（作为游离酸或其碱金属、铵或烷基铵盐）或羟基基团的任何其他前体基团；或其生理上可接受的盐。此外，本发明还包括以下新化合物：2'，3'-二脱氧-3'-氟-2-氟腺苷、2'，3'-二脱氧-3'-氟-6-硫代鸟苷、2'，3'-二脱氧-3'-氟-2,6-二氨基嘌呤核苷、2'，3'-二脱氧-3'-氟-2-氨基嘌呤核苷、2'，3'-二脱氧-3'-氟-5-氨甲基尿苷、2'，3'-二脱氧-3'-氟-5-叠氮甲基尿苷和2'，3'-二脱氧-3'-氟-5-羟甲基尿苷。
• Preparation of 3'-substituted-2',3'-dideoxynucleosides and
  申请人：Emory University

  公开号：US05432273A1

  公开（公告）日：1995-07-11

  A process for the preparation of 3'-substituted-2',3'-dideoxynucleosides is provided that utilizes inexpensive, non-carbohydrate, acyclic, achiral starting materials and that proceeds with high enantiomeric and stereochemical control. The method can be used to prepare the pharmaceutically important compounds 3'-azido-3'-deoxythymidine, 3'-azido-2',3'-dideoxyuridine, 3'-fluoro-3'-deoxythymidine, and 3'-fluoro-3'-deoxyuridine.

  提供一种制备3'-取代-2'，3'-二脱氧核苷的方法，该方法利用廉价、非碳水化合物、无手性起始物质，并具有高对映体和立体化学控制。该方法可用于制备具有药用价值的化合物3'-偶氮基-3'-脱氧胸腺嘧啶、3'-偶氮基-2'，3'-二脱氧尿嘧啶、3'-氟-3'-脱氧胸腺嘧啶和3'-氟-3'-脱氧尿嘧啶。
• 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.
• Hydrofluorination of anhydrothymidine via soluble aluminum derivatives
  作者：Kenneth Green、David M. Blum

  DOI：10.1016/s0040-4039(00)71244-5

  日期：1991.5

  A new method to stereospecifically hydrofluorinate anhydrothymidine has been discovered which allows the product to be obtained in higher yields than the current literature method.