diethyl (2-amino-9-((2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyltetrahydrofuran-2-yl)-9H-purin-6-yl)phosphonate | 1345969-94-9

• 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: diethyl (2-amino-9-((2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyltetrahydrofuran-2-yl)-9H-purin-6-yl)phosphonate
• 英文别名: (2R,3R,4R,5R)-2-(2-amino-6-diethoxyphosphorylpurin-9-yl)-5-(hydroxymethyl)-3-methyloxolane-3,4-diol
• CAS: 1345969-94-9
• 化学式: C₁₅H₂₄N₅O₇P
• 分子量: 417.359
• InChiKey: KHXCCFOXGSVVRJ-YWGZHDIYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  28
• 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：
  175
• 氢给体数：
  4
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  N-(氯苯氧基氧化膦基)-L-丙氨酸异丙酯 、 diethyl (2-amino-9-((2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyltetrahydrofuran-2-yl)-9H-purin-6-yl)phosphonate 在 N-甲基咪唑 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 3.0h， 以77%的产率得到isopropyl ((((2R,3R,4R,5R)-5-(2-amino-6-(diethoxyphosphoryl)-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)-L-alaninate
  参考文献：
  名称：

  Synthesis and Evaluation of 2,6-Modified Purine 2′-C-Methyl Ribonucleosides as Inhibitors of HCV Replication

  摘要：

  A variety of 2,6-modified purine 2'-C-methylribonucleosides and their phosphoramidate prodrugs were synthesized and evaluated for inhibition of HCV RNA replication in Huh-7 cells and for cytotoxicity in various cell lines. Cellular pharmacology and HCV polymerase incorporation studies on the most potent and selective compound are reported.

  DOI：

  10.1021/acsmedchemlett.5b00402
• 作为产物：
  描述：

  2-C-甲基-D-核糖酸-1,4-内酯 在 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 、 lithium tri-t-butoxyaluminum hydride 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 104.0h， 生成 diethyl (2-amino-9-((2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyltetrahydrofuran-2-yl)-9H-purin-6-yl)phosphonate
  参考文献：
  名称：

  Synthesis and Evaluation of 2,6-Modified Purine 2′-C-Methyl Ribonucleosides as Inhibitors of HCV Replication

  摘要：

  A variety of 2,6-modified purine 2'-C-methylribonucleosides and their phosphoramidate prodrugs were synthesized and evaluated for inhibition of HCV RNA replication in Huh-7 cells and for cytotoxicity in various cell lines. Cellular pharmacology and HCV polymerase incorporation studies on the most potent and selective compound are reported.

  DOI：

  10.1021/acsmedchemlett.5b00402

文献信息

• Synthesis of purine modified 2′-C-methyl nucleosides as potential anti-HCV agents
  作者：Hong-wang Zhang、Longhu Zhou、Steven J. Coats、Tamara R. McBrayer、Phillip M. Tharnish、Lavanya Bondada、Mervi Detorio、Sarah A. Amichai、Melissa D. Johns、Tony Whitaker、Raymond F. Schinazi

  DOI：10.1016/j.bmcl.2011.09.034

  日期：2011.11

  Based on the anti-hepatitis C activity of 2′-C-methyl-adenosine and 2′-C-methyl-guanosine, a series of new modified purine 2′-C-methyl nucleosides was prepared as potential anti-hepatitis C virus agents. Herein, we report the synthesis of both 6-modified and 2-modified purine 2′-C-methyl-nucleosides along with their anti-HCV replication activity and cytotoxicity in different cells.

  基于2' - C-甲基-腺苷和2' - C-甲基-鸟苷的抗丙型肝炎活性，制备了一系列新型修饰嘌呤2'- C-甲基核苷作为潜在的抗丙型肝炎病毒药物. 在此，我们报告了 6-修饰和 2-修饰的嘌呤 2' - C-甲基-核苷的合成以及它们在不同细胞中的抗 HCV 复制活性和细胞毒性。
• Synthesis and Evaluation of 2,6-Modified Purine 2′-<i>C</i>-Methyl Ribonucleosides as Inhibitors of HCV Replication
  作者：Longhu Zhou、Hongwang Zhang、Sijia Tao、Maryam Ehteshami、Jong Hyun Cho、Tamara R. McBrayer、Philip Tharnish、Tony Whitaker、Franck Amblard、Steven J. Coats、Raymond F. Schinazi

  DOI：10.1021/acsmedchemlett.5b00402

  日期：2016.1.14

  A variety of 2,6-modified purine 2'-C-methylribonucleosides and their phosphoramidate prodrugs were synthesized and evaluated for inhibition of HCV RNA replication in Huh-7 cells and for cytotoxicity in various cell lines. Cellular pharmacology and HCV polymerase incorporation studies on the most potent and selective compound are reported.