(2R,3R,4R,5R)-2-[2-amino-6-(3-methoxypropoxy)purin-9-yl]-5-(hydroxymethyl)-3-methyl-tetrahydrofuran-3,4-diol | 1338700-48-3

• 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-(3-methoxypropoxy)purin-9-yl]-5-(hydroxymethyl)-3-methyl-tetrahydrofuran-3,4-diol
• 英文别名: (2R,3R,4R,5R)-2-[2-amino-6-(3-methoxypropoxy)purin-9-yl]-5-(hydroxymethyl)-3-methyloxolane-3,4-diol
• CAS: 1338700-48-3
• 化学式: C₁₅H₂₃N₅O₆
• 分子量: 369.378
• InChiKey: GQRGVXVOJGVBAL-YWGZHDIYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  158
• 氢给体数：
  4
• 氢受体数：
  10

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-(3-methoxypropoxy)purin-9-yl]-5-(hydroxymethyl)-3-methyl-tetrahydrofuran-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-(3-methoxypropoxy)purin-9-yl]-3,4-dihydroxy-4-methyl-tetrahydrofuran-2-yl]methoxy-(1-naphthyloxy)phosphoryl]amino]propanoate
  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：

  3-甲氧基-1-丙醇 、 6-氯-9-(2-C-甲基-beta-D-呋喃核糖基)-9H-嘌呤-2-胺 在 sodium hydride 作用下， 以50%的产率得到(2R,3R,4R,5R)-2-[2-amino-6-(3-methoxypropoxy)purin-9-yl]-5-(hydroxymethyl)-3-methyl-tetrahydrofuran-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

• 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.