(2S)-tetrahydro-2H-pyran-4-yl 2-(chloro(naphthalene-1-yloxy)phosphorylamino)propanoate | 1234491-76-9

• 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: (2S)-tetrahydro-2H-pyran-4-yl 2-(chloro(naphthalene-1-yloxy)phosphorylamino)propanoate
• 英文别名: 1-naphthyl(tetrahydropyroxy-L-alaninyl)phosphorochloridate；(2S)-tetrahydro-2H-pyran-4-yl 2-(chloro(naphthalen-1-yloxy)phosphorylamino)propanoate；naphthalen-1-yl (tetrahydropyroxy-L-alaninyl)phosphorochloridate；oxan-4-yl (2S)-2-[[chloro(naphthalen-1-yloxy)phosphoryl]amino]propanoate
• CAS: 1234491-76-9
• 化学式: C₁₈H₂₁ClNO₅P
• 分子量: 397.795
• InChiKey: IJIMZXIAJFXSMG-ABGKOZRJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  73.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S)-tetrahydro-2H-pyran-4-yl 2-(chloro(naphthalene-1-yloxy)phosphorylamino)propanoate 、 5-氟-2'-脱氧脲核苷 在 叔丁基氯化镁 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以1.6%的产率得到5-fluoro-2'-deoxyuridine-5'-O-[1-naphthyl(tetrahydropyroxy-L-alaninyl)]phosphate
  参考文献：
  名称：

  Phosphoramidate ProTides of the Anticancer Agent FUDR Successfully Deliver the Preformed Bioactive Monophosphate in Cells and Confer Advantage over the Parent Nucleoside

  摘要：

  The fluorinated pyrimidine family of nucleosides continues to represent major current chemotherapeutic agents for treating solid tumors. We herein report their phosphate prodrugs, ProTides, as promising new derivatives, which partially bypass the dependence of the current drugs on active transport and nucleoside kinase-mediated activation. They are also resistant to metabolic deactivation by phosphorolytic enzymes. We report 39 ProTides of the fluorinated pyrimidine FUDR with variation in the aryl, ester, and amino acid. regions. Notably, only certain ProTide motifs are successful in delivering the nucleoside monophosphate into intact cells. We also find that the ProTides retain activity in mycoplasma infected cells, unlike FUDR. Data suggest these compounds to be worthy of further progression.

  DOI：

  10.1021/jm200815w

文献信息

• [EN] SUBSTITUTED PURINE NUCLEOSIDES, PHOSPHORAMIDATE AND PHOSPHORDIAMIDATE DERIVATIVES FOR TREATMENT OF VIRAL INFECTIONS<br/>[FR] NUCLÉOSIDES DE PURINE SUBSTITUÉS, DÉRIVÉS PHOSPHORAMIDATE ET PHOSPHORDIAMIDATE DESTINÉS À TRAITER DES INFECTIONS VIRALES
  申请人：INHIBITEX INC

  公开号：WO2013070887A1

  公开（公告）日：2013-05-16

  This invention is directed to compounds of Formula (I) having the structure that are useful in the treatment of viral infections in mammals, particularly in humans, mediated, at least in part, by a virus in the Flaviviridae family of viruses.

  这项发明涉及具有结构的化合物（I）的公式，这些化合物在哺乳动物，特别是人类中，用于治疗由黄病毒科病毒介导的病毒感染。
• Phosphoramidate Derivatives of Guanosine Nucleoside Compunds for Treatment of Viral Infections
  申请人：Chamberlain Stanley

  公开号：US20120052046A1

  公开（公告）日：2012-03-01

  Phosphoramidate compounds derived from guanine bases having enhanced therapeutic potency are provided, and these compounds in particular have enhanced potency with respect to treatment of viral infections, such as hepatitis C virus. Pharmaceutical compositions, methods of preparing the compounds, and methods of using the compounds and compositions to treat viral infections are also provided.

  本发明提供了从鸟嘌呤碱基衍生的磷酰胺化合物，具有增强的治疗效力，特别是对于治疗病毒感染，如丙型肝炎病毒，具有增强的效力。本发明还提供了制备该化合物的制药组合物、制备该化合物的方法以及使用该化合物和组合物治疗病毒感染的方法。
• Substituted Purine Nucleosides, Phosphoramidate and Phosphordiamidate Derivatives for Treatment if Viral Infections
  申请人：INHIBITEX, INC.

  公开号：US20140286903A1

  公开（公告）日：2014-09-25

  This invention is directed to compounds of Formula (I) having the structure that are useful in the treatment of viral infections in mammals, particularly in humans, mediated, at least in part, by a virus in the Flaviviridae family of viruses.

  本发明涉及具有结构的I式化合物，其在哺乳动物，特别是人类中，对通过Flaviviridae病毒家族中的病毒介导的病毒感染的治疗中是有用的。
• PHOSPHORAMIDATE DERIVATIVES OF GUANOSINE NUCLEOSIDE COMPOUNDS FOR TREATMENT OF VIRAL INFECTIONS
  申请人：University College Cardiff Consultants, Ltd.

  公开号：EP2385951A2

  公开（公告）日：2011-11-16
• US8759318B2
  申请人：——

  公开号：US8759318B2

  公开（公告）日：2014-06-24