(4S)-2'-deoxy-2',2'-difluoro-3,4,5,6-tetrahydrouridine | 1141397-81-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (4S)-2'-deoxy-2',2'-difluoro-3,4,5,6-tetrahydrouridine
• 英文别名: (4S)-1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one
• CAS: 1141397-81-0
• 化学式: C₉H₁₄F₂N₂O₅
• 分子量: 268.217
• InChiKey: VUDZSIYXZUYWSC-XZBKPIIZSA-N

物化性质

• 熔点：
  59-62 °C
• 沸点：
  597.7±50.0 °C(Predicted)
• 密度：
  1?+-.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：
  0.89
• 拓扑面积：
  102
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2'-Deoxy-2',2'-difluoro-5,6-dihydrouridine 在 甲醇 、 sodium tetrahydroborate 、 cerium(III) chloride heptahydrate 作用下， 以 二氯甲烷 为溶剂， 生成 西达尿苷 、 (4S)-2'-deoxy-2',2'-difluoro-3,4,5,6-tetrahydrouridine
  参考文献：
  名称：

  [EN] AN IMPROVED PROCESS FOR THE PREPARATION OF (4R)-1-[(2R,4R,5R)-3,3-DIFLUORO-4-HYDROXY-5-(HYDROXYMETHYL) OXOLAN-2-YL]-4-HYDROXY-1,3-DIAZINAN-2ONE AND ITS INTERMEDIATE COMPOUNDS
  [FR] PROCÉDÉ AMÉLIORÉ DE PRÉPARATION DE (4R)-1-[(2R,4R,5R)-3,3-DIFLUORO-4-HYDROXY-5-(HYDROXYMÉTHYL)OXOLAN-2-YL]-4-HYDROXY-1,3-DIAZINAN-2-ONE ET DE SES COMPOSÉS INTERMÉDIAIRES

  摘要：

  The present invention relates to an improved process for the preparation of (4R)-1-[(2R, 4R, 5R)-3,3-difluoro-4-hydroxy-5- (hydroxymethyl) oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one compound of formula-1 and its intermediate compounds. [Formula should be inserted here]. The present invention also relates to the process for the purification of (4R)-1-[(2R, 4R, 5R)-3,3-difluoro-4-hydroxy-5- (hydroxymethyl) oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one compound of formula-1 to get pure compound of formula-1.

  公开号：

  WO2022254457A1

文献信息

• Design, Synthesis, and Pharmacological Evaluation of Fluorinated Tetrahydrouridine Derivatives as Inhibitors of Cytidine Deaminase
  作者：Dana Ferraris、Bridget Duvall、Greg Delahanty、Bipin Mistry、Jesse Alt、Camilo Rojas、Christopher Rowbottom、Kristen Sanders、Edgar Schuck、Kuan-Chun Huang、Sanjeev Redkar、Barbara B. Slusher、Takashi Tsukamoto

  DOI：10.1021/jm401856k

  日期：2014.3.27

  Several 2′-fluorinated tetrahydrouridine derivatives were synthesized as inhibitors of cytidine deaminase (CDA). (4R)-2′-Deoxy-2′,2′-difluoro-3,4,5,6-tetrahydrouridine (7a) showed enhanced acid stability over tetrahydrouridine (THU) 5 at its N-glycosyl bond. As a result, compound 7a showed an improved oral pharmacokinetic profile with a higher and more reproducible plasma exposure in rhesus monkeys

  合成了几种2'-氟化的四氢尿苷衍生物作为胞苷脱氨酶（CDA）的抑制剂。（4R）-2′-脱氧-2′，2′-二氟-3,4,5,6-四氢尿苷（7a）在其N-糖基键上显示出比四氢尿苷（THU）5更高的酸稳定性。结果，与5相比，化合物7a在恒河猴中表现出改善的口服药代动力学特征，血浆暴露量更高且可重现。7a与地西他滨（一种CDA底物）的共同给药可提高恒河猴中地西他滨的血浆水平。这些结果表明，化合物7a中可以作为酸稳定的替代5 作为受CDA介导的新陈代谢作用的药物的药物增强剂。
• [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。
• Synthetic route to 2′-deoxy-2′,2′-difluorotetrahydrouridines
  申请人：Otsuka Pharmaceutical Co., Ltd.

  公开号：US11028119B2

  公开（公告）日：2021-06-08

  The present invention relates to methods and intermediates for synthesizing 2′-deoxy-2′,2′-difluorotetrahydrouridine compounds.

  本发明涉及合成 2′-脱氧-2′,2′-二氟四氢尿苷化合物的方法和中间体。
• 2'-FLUORO-2'-DEOXYTETRAHYDROURIDINES AS CYTIDINE DEAMINASE INHIBITORS
  申请人：Eisai Inc.

  公开号：EP2207786B1

  公开（公告）日：2012-03-07
• Certain Compounds, Compositions and Methods
  申请人：Hamilton Gregory S.

  公开号：US20090137521A1

  公开（公告）日：2009-05-28

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