4-氨基-1-(2-脱氧-2-氟-beta-D-阿拉伯呋喃基)-2(1H)-嘧啶酮 | 56632-83-8

• 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: 4-氨基-1-(2-脱氧-2-氟-beta-D-阿拉伯呋喃基)-2(1H)-嘧啶酮
• 英文名称: 1-(2-fluoro-2-deoxy-β-D-arabinofuranosyl)cytosine
• 英文别名: 2’-deoxy-2’-fluoro-arabinocytidine；2'-deoxy-2'-fluoroarabinocytidine；2'-deoxy-2'-fluoroarabinocytosine；FAC；4-amino-1-(2-fluoro-β-D-2-deoxy-arabinofuranosyl)-1H-pyrimidin-2-one；1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)cytosine；2'-Fluoro-2'-deoxy-arabinofuranosyl-cytidine；4-amino-1-[(2R,3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one
• CAS: 56632-83-8
• 化学式: C₉H₁₂FN₃O₄
• 分子量: 245.21
• InChiKey: NVZFZMCNALTPBY-PXBUCIJWSA-N

物化性质

• 熔点：
  136-138 °C
• 沸点：
  500.1±60.0 °C(Predicted)
• 密度：
  1.82±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  5

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  应存放在室温、避光且充满惰性气体的环境中。

制备方法与用途

4-氨基-1-(2-脱氧-2-氟-β-D-阿拉伯呋喃基)-2(1H)-嘧啶酮用作研究用途的化合物。

反应信息

• 作为反应物：
  描述：

  4-氨基-1-(2-脱氧-2-氟-beta-D-阿拉伯呋喃基)-2(1H)-嘧啶酮 在 吡啶 、 偶氮二异丁腈 、 三正丁基氢锡 、 sodium methylate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 4.5h， 生成 1-(2,3-二脱氧-2-氟呋喃戊糖基)胞嘧啶
  参考文献：
  名称：

  Synthesis and anti-HIV-1 activity of 2'-"up"-fluoro analogs of active anti-AIDS nucleosides 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxycytidine (DDC)

  摘要：

  1-(3-Azido-2,3-dideoxy-2-fluoro-beta-D-arabinofuranosyl)thymine (6, F-AZT) and 1-(2,3-dideoxy-2-fluoro-beta-D-threopentofuranosyl)cytosine (12, F-DDC) were synthesized from the potent antiherpes virus nucleosides 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)thymine (1, FMAU) and 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine (FIAC) in the hope that introduction of a 2-"up"-fluoro substituent might potentiate the anti-HIV activity of AZT and DDC. FMAU (1) was converted in three steps into 2,3'-anhydro-1-(2-fluoro-2-deoxy-5-O-trityl-beta-D-lyxofuranosyl)thymine (4), which when treated with NaN3 followed by detritylation afforded 6. F-DDC was prepared by two methods. Tritylation of FIAC followed by treatment of the product with thiocarbonyldimidazole afforded the 5'-O-trityl-3'-O-(imidazolyl)thiocarbonyl nucleoside 9. Upon radical reduction of 9 with Bu3SnH and AIBN, 5'-O-trityl-DDC 10 was obtained. Compound 10 was detritylated to give 12, which (when obtained by this procedure) resisted crystallization, but the diacetate 12' was obtained in crystalline form. Alternatively, FAC (14) was converted into N4,O5'-dibenzoyl derivative 15, which was treated with thiocarbonyldiimidazole. Reduction of 16 with Bu3SnH/AIBN followed by debenzoylation afforded 12, which was obtained in crystalline form. F-AZT did not exhibit any significant activity against the human immunodeficiency virus (HIV) in vitro. F-DDC, however, showed activity against HIV-1, but the therapeutic index is much inferior to that of AZT.

  DOI：

  10.1021/jm00170a016
• 作为产物：
  描述：

  2-脱氧-2-氟-1,3,5-三苯甲酰基-alpha-D-阿拉伯呋喃糖 在 氨 、 氢溴酸 、 溶剂黄146 作用下， 以 甲醇 、 四氯化碳 为溶剂， 生成 4-氨基-1-(2-脱氧-2-氟-beta-D-阿拉伯呋喃基)-2(1H)-嘧啶酮
  参考文献：
  名称：

  一些 2'-FLUORO-2'-DEOXY-3'-C-ETHYNYL 和 3'-C-VINYL-β-D-LYXOFURANOSYL 核苷的合成

  摘要：

  1-(2-Fluoro-2-deoxy-β-D-arabinofuranosyl) 尿嘧啶 (5) 和 1-(2-fluoro-2-deoxy-β-D-arabinofuranosyl) 胞嘧啶 (6) 的合成如前所述。这两种化合物都通过多步序列转化为 2'-氟-2'-脱氧-3'-C-乙炔基和 3'-C-乙烯基-β-D-lyxofuranosyl 核苷（16-19）。所有这些新的核苷都在体外针对七种人类肿瘤细胞系进行了评估。

  DOI：

  10.1081/ncn-200060300

文献信息

• [EN] COMPOSITIONS AND METHODS FOR DELIVERY OF THERAPEUTIC AGENTS<br/>[FR] COMPOSITIONS ET PROCÉDÉS PERMETTANT D'ADMINISTRER DES AGENTS THÉRAPEUTIQUES
  申请人：MODERNATX INC

  公开号：WO2017099823A1

  公开（公告）日：2017-06-15

  This disclosure provides improved lipid-based compositions, including lipid nanoparticle compositions, and methods of use thereof for delivering agents in vivo including nucleic acids and proteins. These compositions are not subject to accelerated blood clearance and they have an improved toxicity profile in vivo.

  这项披露提供了改进的基于脂质的组合物，包括脂质纳米粒子组合物，以及它们用于体内传递药剂的方法，包括核酸和蛋白质。这些组合物不受加速血清清除的影响，并且它们在体内具有改进的毒性特性。
• [EN] SUBSTITUTED NUCLEOSIDE AND NUCLEOTIDE ANALOGS<br/>[FR] NUCLEOSIDE SUBSTITUE ET ANALOGUES NUCLEOTIDIQUES
  申请人：ALIOS BIOPHARMA INC

  公开号：WO2010108140A1

  公开（公告）日：2010-09-23

  Disclosed herein are nucleotide analogs with protected phosphates, methods of synthesizing nucleotide analogs with protected phosphates and methods of treating diseases and/or conditions such as viral infections, cancer, and/or parasitic diseases with the nucleotide analogs with protected phosphates.

  本文披露了具有保护磷酸酯基团的核苷酸类似物，以及合成具有保护磷酸酯基团的核苷酸类似物的方法，以及利用具有保护磷酸酯基团的核苷酸类似物治疗病毒感染、癌症和/或寄生虫病等疾病和/或症状的方法。
• [EN] MODIFIED NUCLEIC ACID MOLECULES AND USES THEREOF<br/>[FR] MOLÉCULES D'ACIDE NUCLÉIQUE MODIFIÉES ET LEURS UTILISATIONS
  申请人：MODERNA THERAPEUTICS INC

  公开号：WO2014093924A1

  公开（公告）日：2014-06-19

  The present disclosure provides modified nucleosides, nucleotides, and nucleic acids, and methods of using them.

  本公开提供了经修改的核苷、核苷酸和核酸，以及它们的使用方法。
• [EN] TRANSLATIONAL ENHANCERS AND RELATED METHODS<br/>[FR] AMPLIFICATEURS DE TRADUCTION ET PROCÉDÉS ASSOCIÉS
  申请人：EFFECTOR THERAPEUTICS INC

  公开号：WO2021001739A1

  公开（公告）日：2021-01-07

  The present disclosure relates to novel translational enhancers comprising an eukaryotic initiation factor 4E (eIF4E) ligand attached to a dinucleotide. The present disclosure also relates to RNA molecules (e.g., mRNAs) comprising the novel translational enhancers, which imparts properties to the RNA molecules that are advantageous to therapeutic development, methods of using RNA molecules comprising such novel translational enhancers for therapeutic uses, as well as kits containing the translational enhancers.

  本公开涉及包含连接到二核苷酸的真核起始因子4E（eIF4E）配体的新型转译增强剂。本公开还涉及包含这些新型转译增强剂的RNA分子（例如mRNA），这些RNA分子赋予了对治疗开发有利的特性，以及使用包含这些新型转译增强剂的RNA分子进行治疗用途的方法，以及包含转译增强剂的试剂盒。
• [EN] 2 ' -FLU0R0-2 ' -DEOXYTETRAHYDROURIDINES AS CYTIDINE DEAMINASE INHIBITORS<br/>[FR] CERTAINS COMPOSÉS, COMPOSITIONS ET PROCÉDÉS
  申请人：EISAL CORP OF NORTH AMERICA

  公开号：WO2009052287A1

  公开（公告）日：2009-04-23

  The present invention provides certain tetrahydrouridine derivative compounds, pharmaceutical compositions and kits comprising such compounds, and methods of making and using such compounds.

  本发明提供了某些四氢尿嘧啶衍生物化合物、包含这些化合物的药物组合物和试剂盒，以及制备和使用这些化合物的方法。