1-(2-脱氧-2-氟-beta-D-阿拉伯糖呋喃基)-5-氟-2,4(1H,3H)-嘧啶二酮 | 69123-95-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 中文名称: 1-(2-脱氧-2-氟-beta-D-阿拉伯糖呋喃基)-5-氟-2,4(1H,3H)-嘧啶二酮
• 中文别名: 1-(2-脱氧-2-氟-beta-D-阿拉伯呋喃糖基)-5-氟-2,4(1H,3H)-嘧啶二酮
• 英文名称: 2',5-difluoro-1-arabinosyluracil (FFara-Ura)
• 英文别名: FFARA-URA；5-fluoro-1-(2-fluoro-β-D-2-deoxy-arabinofuranosyl)-1H-pyrimidine-2,4-dione；1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-fluorouracil；5-Fluoro-1-((2R,3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione；5-fluoro-1-[(2R,3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione
• CAS: 69123-95-1
• 化学式: C₉H₁₀F₂N₂O₅
• 分子量: 264.186
• InChiKey: QURNODSOJKSTBM-BYPJNBLXSA-N

物化性质

• 熔点：
  168-170 °C(Solv: chloroform (67-66-3); methanol (67-56-1))
• 密度：
  1.69±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  99.1
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(2-脱氧-2-氟-beta-D-阿拉伯糖呋喃基)-5-氟-2,4(1H,3H)-嘧啶二酮 在 咪唑 、 三苯基膦 、 碘 作用下， 以 四氢呋喃 为溶剂， 以35.31 %的产率得到5-fluoro-1-((2R,3S,4R,5S)-3-fluoro-4-hydroxy-5-(iodomethyl)tetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  [EN] COMPOUNDS AND METHODS FOR TREATING DISEASE
  [FR] COMPOSÉS ET MÉTHODES POUR TRAITER UNE MALADIE

  摘要：

  The invention provides compounds, compositions and methods for treating medical disorders, such as cancer, an autoimmune disorder, and/or a neurological disorder, and inhibiting LINE1 reverse transcriptase and/or HERV-K reverse transcriptase using a compound according to Formula I or a pharmaceutically acceptable salt thereof, or a related compound provided herein.

  公开号：

  WO2023178133A1
• 作为产物：
  描述：

  ((2R,3R,4S,5R)-3-(benzoyloxy)-4-fluoro-5-(5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl benzoate 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 以75.7 %的产率得到1-(2-脱氧-2-氟-beta-D-阿拉伯糖呋喃基)-5-氟-2,4(1H,3H)-嘧啶二酮
  参考文献：
  名称：

  [EN] COMPOUNDS AND METHODS FOR TREATING DISEASE
  [FR] COMPOSÉS ET MÉTHODES POUR TRAITER UNE MALADIE

  摘要：

  The invention provides compounds, compositions and methods for treating medical disorders, such as cancer, an autoimmune disorder, and/or a neurological disorder, and inhibiting LINE1 reverse transcriptase and/or HERV-K reverse transcriptase using a compound according to Formula I or a pharmaceutically acceptable salt thereof, or a related compound provided herein.

  公开号：

  WO2023178133A1

文献信息

• A general synthesis of 2?-deoxy-2?-[18F]fluoro-1-?-D-arabinofuranosyluracil and its 5-substituted nucleosides
  作者：Mian M. Alauddin、Peter S. Conti、John D. Fissekis

  DOI：10.1002/jlcr.637

  日期：2003.3.30

  Several 2′-deoxy-2′-[18F]fluoro-1-β-D-arabinofuranosyluracil derivatives have been synthesized. Coupling of 1-bromo-2-deoxy-2-[18F]fluoro-3,5-di-O-benzoyl-α-D-arabinofuranose 2 with protected uracil derivatives 3a–e followed by hydrolysis and high-performance liquid chromatography purification produced the radiolabeled nucleosides 4a–e in 15–30% yield (d. c.), >99% radiochemical purity and 55.5–103.6 GBq/µmol specific activities. Copyright © 2003 John Wiley & Sons, Ltd.

  我们合成了几种 2′-脱氧-2′-[18F]氟-1-β-D-阿拉伯呋喃糖基尿嘧啶衍生物。将 1-溴-2-脱氧-2-[18F]氟-3,5-二-O-苯甲酰基-α-D-阿拉伯呋喃糖 2 与受保护的尿嘧啶衍生物 3a-e 偶联，然后进行水解和高效液相色谱纯化，得到了放射性标记的核苷 4a-e，收率为 15-30% (d.c.)，放射化学纯度大于 99%，比活度为 55.5-103.6 GBq/µmol。Copyright © 2003 John Wiley & Sons, Ltd. All Rights Reserved.
• Synthesis of 2′-Deoxy-2′-β-fluoro-4′-azido-5-fluorouridine as a Potential Anti-HIV Agent
  作者：Wenquan Yu、Junbiao Chang、Jiao Hou、Jian-Hua Wang

  DOI：10.1055/a-2213-2408

  日期：2024.4

  2′-Deoxy-2′-β-fluoro-4′-azido-5-fluorouridine, a new pyrimidine nucleoside analogue of azvudine (FNC), was designed and synthesized. The synthesis of this nucleoside analogue was achieved by bromination of 1,3,5-O-tribenzoyl-2-deoxy-2-fluoro-d-arabinofuranoside, followed by reaction with silylated 5-fluorouracil and further modifications of the sugar moiety, in a 7.6% overall yield over nine steps

  设计并合成了阿兹夫定（FNC）的新型嘧啶核苷类似物2'-脱氧-2'-β-氟-4'-叠氮基-5-氟尿苷。该核苷类似物的合成是通过 1,3,5- O-三苯甲酰基-2-脱氧-2-氟-d-阿拉伯呋喃糖苷，然后与甲硅烷基化的 5-氟尿嘧啶反应并进一步修饰糖部分，经过九个步骤，总产率为 7.6%。该产品对HEK293T细胞中的HIV-1感染表现出良好的抗病毒活性。
• 5-Substituted 1-(2'-deoxy-2'-substituted-beta-D-arabinofuranosyl) pyrimidine nucleosides and pharmaceutical compositions containing them
  申请人：Sloan-Kettering Institute For Cancer Research

  公开号：EP0010205A1

  公开（公告）日：1980-04-30

  1. Pyrimidine nucleosides exhibiting anti-viral and anti-tumor effects have the formula wherein A is OR', SR', NR3R4 or NHacyl wherein R' and R' are the same or different and are hydrogen, lower alkyl of 1 to 7 carbon atoms, aralkyl, or aryl; NHacyl is alkanoyl or aroyl amide; B is oxygen or sulfur; X is halogen, alkylsulfonyl or arylsulfonyl; Y is halogen, amino, monoalkyl- or monoaralkylamino, dialkylamino, aminomethyl, hydroxymethyl, lower alkyl, aryl, aralkyl, vinyl and substituted vinyl or ethynyl and substituted ethynyl; Z is methyne or nitrogen; R1 and R2 are the same or different and are hydrogen acyl or aroyl.

  1.具有抗病毒和抗肿瘤作用的嘧啶核苷的化学式为 其中 A是OR'、SR'、NR3R4或NHacyl，其中R'和R'相同或不同，并且是氢、1至7个碳原子的低级烷基、芳基或芳基； NHacyl 是烷酰基或芳基酰胺； B 是氧或硫； X 是卤素、烷基磺酰基或芳基磺酰基； Y 是卤素、氨基、单烷基或单芳基氨基、二烷基氨基、氨甲基、羟甲基、低级烷基、芳基、芳烷基、乙烯基和取代乙烯基或乙炔基和取代乙炔基； Z 是甲基或氮； R1 和 R2 相同或不同，并且是氢酰基或芳基。
• Mechanism of action of 2',5-difluoro-1-arabinosyluracil
  作者：Akira Matsuda、Kyoichi A. Watanabe、Jack J. Fox

  DOI：10.1021/jm00362a012

  日期：1983.8

  Results are described which demonstrate that the cytotoxic action of 2',5-difluoro-1-arabinosyluracil (FFara-Ura) involves conversion to the corresponding 5'-phosphate, FFara-UMP, and subsequent inhibition of thymidylate synthetase. The evidence for this is as follows: (a) cells lacking thymidine kinase are 120-fold more resistant to FFara-Ura; (b) FFara-Ura markedly inhibits the incorporation of 2'-deoxyuridine (dUrd) into DNA with little or no effect on 2'-deoxythymidine (dThd) incorporation; (c) FFara-Ura causes changes in deoxynucleoside triphosphate pool sizes, which are characteristic of specific inhibition of dTMP synthetase. Binding and spectroscopic studies demonstrate that FFara-UMP inactivates dTMP synthetase from Lactobacillus casei in a manner analogous to that described for FdUMP. Furthermore, FFara-Ura is not a substrate for the pyrimidine phosphorylases; the significance of this finding with regard to the possible chemotherapeutic utility of FFara-Ura is discussed.
• MEDICAL IMPLANTS AND FIBROSIS-INDUCING AGENTS
  申请人：ANGIOTECH INTERNATIONAL AG

  公开号：EP1691852A2

  公开（公告）日：2006-08-23