4-amino-1-((2R,3S,4S,5R)-5-azido-4-fluoro-3-hydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-1H-pyrimidin-2-one

• 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: 4-amino-1-((2R,3S,4S,5R)-5-azido-4-fluoro-3-hydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-1H-pyrimidin-2-one
• 英文别名: 1-(4'-azido-3'-deoxy-3'-fluoro-β-D-ribofuranosyl)cytosine；3'-deoxy-3'-alpha-fluoro-4'-azidocytidine；4'-C-azido-3'-deoxy-3'-fluorocytidine；4-amino-1-[(2R,3S,4S,5R)-5-azido-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-one；4-amino-1-[(2R,3S,4S,5R)-5-azido-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one
• 化学式: C₉H₁₁FN₆O₄
• 分子量: 286.223
• InChiKey: PCPGVUKMIADCCP-JVZYCSMKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  123
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-amino-1-((2R,3S,4S,5R)-5-azido-4-fluoro-3-hydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-1H-pyrimidin-2-one 在 吡啶 、 叔丁基氯化镁 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 7.5h， 生成 (S)-2-[[(2R,3S,4S,5R)-5-(4-amino-2-oxo-2H-pyrimidin-1-yl)-2-azido-3-fluoro-4-hydroxy-tetrahydro-furan-2-ylmethoxy]-(naphthalen-1-yloxy)-phosphorylamino]-propionic acid isopropyl ester
  参考文献：
  名称：

  [EN] 4'-AZIDO, 3'-FLUORO SUBSTITUTED NUCLEOSIDE DERIVATIVES AS INHIBITORS OF HCV RNA REPLICATION
  [FR] DÉRIVÉS NUCLÉOSIDIQUES 4'-AZIDO, 3'-FLUORO SUBSTITUÉS EN TANT QU'INHIBITEURS DE LA RÉPLICATION DE L'ARN DU VHC

  摘要：

  本发明涉及使用式(I)的核苷衍生物，其中符号如规范所述，以及其药学上可接受的盐，以及含有这种化合物的药物组合物。

  公开号：

  WO2013092447A1
• 作为产物：
  描述：

  在 ammonium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 以50 mg的产率得到4-amino-1-((2R,3S,4S,5R)-5-azido-4-fluoro-3-hydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-1H-pyrimidin-2-one
  参考文献：
  名称：

  [EN] 4'-AZIDO, 3'-FLUORO SUBSTITUTED NUCLEOSIDE DERIVATIVES AS INHIBITORS OF HCV RNA REPLICATION
  [FR] DÉRIVÉS NUCLÉOSIDIQUES 4'-AZIDO, 3'-FLUORO SUBSTITUÉS EN TANT QU'INHIBITEURS DE LA RÉPLICATION DE L'ARN DU VHC

  摘要：

  本发明涉及使用式(I)的核苷衍生物，其中符号如规范所述，以及其药学上可接受的盐，以及含有这种化合物的药物组合物。

  公开号：

  WO2013092447A1

文献信息

• AZIDO NUCLEOSIDES AND NUCLEOTIDE ANALOGS
  申请人：Beigelman Leonid

  公开号：US20120070415A1

  公开（公告）日：2012-03-22

  Disclosed herein are nucleosides, nucleotides and analogs thereof, pharmaceutical compositions that include one or more of nucleosides, nucleotides and analogs thereof, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an infection from a paramyxovirus and/or an orthomyxovirus, with a nucleoside, a nucleotide and an analog thereof. Examples of viral infections include a respiratory syncytial viral (RSV) and influenza infection.

  本文披露了核苷、核苷酸及其类似物，包括一个或多个核苷、核苷酸及其类似物的药物组合物，以及合成它们的方法。本文还披露了利用核苷、核苷酸和其类似物来改善和/或治疗疾病和/或状况的方法，包括来自副黏病毒和/或正黏病毒的感染。病毒感染的例子包括呼吸道合胞病毒（RSV）和流感感染。
• 4'-AZIDO, 3'-FLUORO SUBSTITUTED NUCLEOSIDE DERIVATIVES AS INHIBITORS OF HCV RNA REPLICATION
  申请人：Hoffmann-La Roche Inc.

  公开号：US20140369959A1

  公开（公告）日：2014-12-18

  The present invention relates to the use of nucleoside derivatives of formula (I) wherein the symbols are as the specification, and of pharmaceutically acceptable salts thereof and to pharmaceutical compositions containing such compounds.

  本发明涉及使用式（I）核苷衍生物及其药学上可接受的盐，以及含有这种化合物的制药组合物。其中符号如规范所述。
• The Design, Synthesis, and Antiviral Activity of Monofluoro and Difluoro Analogues of 4′-Azidocytidine against Hepatitis C Virus Replication: The Discovery of 4′-Azido-2′-deoxy-2′-fluorocytidine and 4′-Azido-2′-dideoxy-2′,2′-difluorocytidine
  作者：David B. Smith、Genadiy Kalayanov、Christian Sund、Anna Winqvist、Tatiana Maltseva、Vincent J.-P. Leveque、Sonal Rajyaguru、Sophie Le Pogam、Isabel Najera、Kurt Benkestock、Xiao-Xiong Zhou、Ann C. Kaiser、Hans Maag、Nick Cammack、Joseph A. Martin、Steven Swallow、Nils Gunnar Johansson、Klaus Klumpp、Mark Smith

  DOI：10.1021/jm801595c

  日期：2009.5.14

  The discovery of 4'-azidocytidine (3) (R1479) (J. Biol. Chem. 2006, 281, 3793; Bioorg. Med. Chem. Lett. 2007, 17, 2570) as a potent inhibitor of RNA synthesis by NS5B (EC50 = 1.28 mu M), the RNA polymerase encoded by hepatitis C virus (HCV), has led to the synthesis and biological evaluation of several monofluoro and difluoro derivatives of 4'-azidocytidine. The most potent compounds in this series were 4'-azido-2'-deoxy-2',2'-difluorocytidine and 4'-azido-2'-deoxy-2'-fluoroarabinocytidine with antiviral EC50 of 66 nM and 24 nM in the HCV replicon system, respectively. The structure-activity relationships within this series were discussed. which led to the discovery of these novel nucleoside analogues with the most potent compound, showing more than a 50-fold increase in antiviral potency as compared to 4'-azidocytidine (3).
• 4'-AZIDO-3'-FLUORO SUBSTITUTED NUCLEOSIDE DERIVATIVES AS INHIBITORS OF HCV RNA REPLICATION
  申请人：Riboscience LLC

  公开号：EP2794628B1

  公开（公告）日：2017-03-29
• 4'-SUBSTITUTED NUCLEOSIDE DERIVATIVES AS INHIBITORS OF HCV RNA REPLICATION
  申请人：Devos Rene Robert

  公开号：US20100003213A1

  公开（公告）日：2010-01-07

  The present invention relates to the use of nucleoside derivatives of formula Ia wherein the symbols are as defined in the specification, and of pharmaceutically acceptable salts thereof and to pharmaceutical compositions containing such compounds.