(R)-2-{[(2R,3S,4R,5R)-5-(4-amino-2-oxo-2H-pyrimidin-1-yl)-2-azido-3,4-dihydroxy-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid benzyl ester

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R)-2-{[(2R,3S,4R,5R)-5-(4-amino-2-oxo-2H-pyrimidin-1-yl)-2-azido-3,4-dihydroxy-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid benzyl ester
• 英文别名: benzyl (2R)-2-[[[(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-2-azido-3,4-dihydroxyoxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate
• 化学式: C₂₅H₂₈N₇O₉P
• 分子量: 601.513
• InChiKey: ZRFDETZQOKPGPY-AFGVBTFXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  42
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  197
• 氢给体数：
  4
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  phenyl (benzyloxy-D-alaninyl)phosphorochloridate 、 盐酸茚罗西生 在 叔丁基氯化镁 作用下， 以 四氢呋喃 为溶剂， 反应 17.0h， 生成 (R)-2-{[(2R,3S,4R,5R)-5-(4-amino-2-oxo-2H-pyrimidin-1-yl)-2-azido-3,4-dihydroxy-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid benzyl ester
  参考文献：
  名称：

  The application of phosphoramidate ProTide technology to the potent anti-HCV compound 4′-azidocytidine (R1479)

  摘要：

  We report the design, synthesis and evaluation of a family of ca 50 phosphoramidate ProTides of the potent anti-HCV compound 4 '-azidocytidine (R1479), with variation on the ester, amino acid and aryl moiety of the ProTide. Sub-mu M inhibitors of HCV emerge. The compounds are all non-cytotoxic in the replicon assay. We herein report detailed SARs for each of the regions of the ProTide. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.05.099

文献信息

• ANTIVIRAL PHOSPHORAMIDATES OF 4'-SUBSTITUTED PRONUCLEOTIDES
  申请人：F.HOFFMANN-LA ROCHE AG

  公开号：EP1928475A2

  公开（公告）日：2008-06-11
• ANTIVIRAL PHOSPHORAMIDATES OF 4'-C-AZIDO-SUBSTITUTED PRONUCLEOTIDES
  申请人：Riboscience LLC

  公开号：EP1928475B1

  公开（公告）日：2018-05-23
• [EN] ANTIVIRAL PHOSPHORAMIDATES<br/>[FR] PHOSPHORAMIDATES ANTIVIRAUX
  申请人：HOFFMANN LA ROCHE

  公开号：WO2007020193A2

  公开（公告）日：2007-02-22

  [EN] The invention provides novel nucleoside compounds of formula I wherein R¹, R^2a, R^2b, R³, R⁴, R⁵, R⁶, R^8a, R⁹ and R¹⁰ are as defined herein which are useful for the treatment of Hepatitis C Virus (HCV) mediated diseases. The invention further provides methods for treatment or prophylaxis of HCV mediated diseases with compounds of formula I and pharmaceutical compositions comprising these compounds. Formula (I)
  [FR] L'invention concerne des nouveaux composés nucléosides de formule (I) dans laquelle R¹, R^2a, R^2b, R³, R⁴, R⁵, R⁶, R^8a, R⁹ et R¹⁰ ont la signification indiquée dans la description, qui sont utilisés pour le traitement de maladies à médiation assurée par le virus de l'hépatite C (VHC). L'invention concerne en outre des méthodes de traitement ou de prophylaxie de maladies à médiation assurée par le VHC à l'aide des composés de formule (I) et des compositions pharmaceutiques comprenant lesdits composés.
• The application of phosphoramidate ProTide technology to the potent anti-HCV compound 4′-azidocytidine (R1479)
  作者：Christopher McGuigan、Mary Rose Kelleher、Plinio Perrone、Sinead Mulready、Giovanna Luoni、Felice Daverio、Sonal Rajyaguru、Sophie Le Pogam、Isabel Najera、Joseph A. Martin、Klaus Klumpp、David B. Smith

  DOI：10.1016/j.bmcl.2009.05.099

  日期：2009.8

  We report the design, synthesis and evaluation of a family of ca 50 phosphoramidate ProTides of the potent anti-HCV compound 4 '-azidocytidine (R1479), with variation on the ester, amino acid and aryl moiety of the ProTide. Sub-mu M inhibitors of HCV emerge. The compounds are all non-cytotoxic in the replicon assay. We herein report detailed SARs for each of the regions of the ProTide. (C) 2009 Elsevier Ltd. All rights reserved.