(2R,3R,4R,5R)-2-(2-amino-6-(benzylamino)-9H-purin-9-yl)-5-(hydroxymethyl)-3-methyltetrahydrofuran-3,4-diol | 1234491-47-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: (2R,3R,4R,5R)-2-(2-amino-6-(benzylamino)-9H-purin-9-yl)-5-(hydroxymethyl)-3-methyltetrahydrofuran-3,4-diol
• 英文别名: (2R,3R,4R,5R)-2-[2-Amino-6-(benzylamino)purin-9-yl]-5-(hydroxymethyl)-3-methyl-tetrahydrofuran-3,4-diol；(2R,3R,4R,5R)-2-[2-amino-6-(benzylamino)purin-9-yl]-5-(hydroxymethyl)-3-methyloxolane-3,4-diol
• CAS: 1234491-47-4
• 化学式: C₁₈H₂₂N₆O₄
• 分子量: 386.41
• InChiKey: HNSFIZVWOFBYAH-MAAOGQSESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  152
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (2S)-neopentyl 2-(chloro(naphthalen-1-yloxy)phosphorylamino)propanoate 、 (2R,3R,4R,5R)-2-(2-amino-6-(benzylamino)-9H-purin-9-yl)-5-(hydroxymethyl)-3-methyltetrahydrofuran-3,4-diol 以 四氢呋喃 为溶剂， 生成 2,2-dimethylpropyl (2S)-2-((((2R,3R,4R,5R)-5-(2-amino-6-benzylamino-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(naphthalen-1-yloxy)phosphorylamino)propionate
  参考文献：
  名称：

  Dual pro-drugs of 2′-C-methyl guanosine monophosphate as potent and selective inhibitors of hepatitis C virus

  摘要：

  We have previously reported the power of combining a 5'-phosphoramidate ProTide, phosphate prodrug, motif with a 6-methoxy purine pro-drug entity to generate highly potent anti-HCV agents, leading to agents in clinical trial. We herein extend this work with the disclosure that a variety of alternative 6-substituents are tolerated. Several compounds exceed the potency of the prior 6-methoxy leads, and in almost every case the ProTide is several orders of magnitude more potent than the parent nucleoside. We also demonstrate that these agents act as pro-drugs of 2'-C-methyl guanosine monophosphate. We have also reported the novel use of hepatocyte cell lysate as an ex vivo model for ProTide metabolism. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.013
• 作为产物：
  描述：

  1,2,3,5-四苯甲酰氧基-2-C-甲基-beta-D-呋喃核糖 在 甲醇 、 三氟甲磺酸三甲基硅酯 、 氨 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 16.0h， 生成 (2R,3R,4R,5R)-2-(2-amino-6-(benzylamino)-9H-purin-9-yl)-5-(hydroxymethyl)-3-methyltetrahydrofuran-3,4-diol
  参考文献：
  名称：

  Dual pro-drugs of 2′-C-methyl guanosine monophosphate as potent and selective inhibitors of hepatitis C virus

  摘要：

  We have previously reported the power of combining a 5'-phosphoramidate ProTide, phosphate prodrug, motif with a 6-methoxy purine pro-drug entity to generate highly potent anti-HCV agents, leading to agents in clinical trial. We herein extend this work with the disclosure that a variety of alternative 6-substituents are tolerated. Several compounds exceed the potency of the prior 6-methoxy leads, and in almost every case the ProTide is several orders of magnitude more potent than the parent nucleoside. We also demonstrate that these agents act as pro-drugs of 2'-C-methyl guanosine monophosphate. We have also reported the novel use of hepatocyte cell lysate as an ex vivo model for ProTide metabolism. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.013

文献信息

• 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。
• [EN] PHOSPHORAMIDATE DERIVATIVES OF GUANOSINE NUCLEOSIDE COMPOUNDS FOR TREATMENT OF VIRAL INFECTIONS<br/>[FR] DÉRIVÉS DE PHOSPHORAMIDATE DE COMPOSÉS GUANOSINE NUCLÉOSIDE POUR LE TRAITEMENT D'INFECTIONS VIRALES
  申请人：UNIV CARDIFF

  公开号：WO2010081082A3

  公开（公告）日：2010-11-25
• US8759318B2
  申请人：——

  公开号：US8759318B2

  公开（公告）日：2014-06-24
• Dual pro-drugs of 2′-C-methyl guanosine monophosphate as potent and selective inhibitors of hepatitis C virus
  作者：Christopher McGuigan、Karolina Madela、Mohamed Aljarah、Arnaud Gilles、Srinivas K. Battina、Changalvala V.S. Ramamurty、C. Srinivas Rao、John Vernachio、Jeff Hutchins、Andrea Hall、Alexander Kolykhalov、Geoffrey Henson、Stanley Chamberlain

  DOI：10.1016/j.bmcl.2011.06.013

  日期：2011.10

  We have previously reported the power of combining a 5'-phosphoramidate ProTide, phosphate prodrug, motif with a 6-methoxy purine pro-drug entity to generate highly potent anti-HCV agents, leading to agents in clinical trial. We herein extend this work with the disclosure that a variety of alternative 6-substituents are tolerated. Several compounds exceed the potency of the prior 6-methoxy leads, and in almost every case the ProTide is several orders of magnitude more potent than the parent nucleoside. We also demonstrate that these agents act as pro-drugs of 2'-C-methyl guanosine monophosphate. We have also reported the novel use of hepatocyte cell lysate as an ex vivo model for ProTide metabolism. (C) 2011 Elsevier Ltd. All rights reserved.