(2R,3R,4R,5R)-2-(6-amino-2-hydrazinyl-9H-purin-9-yl)-5-(hydroxymethyl)-3-methyltetrahydrofuran-3,4-diol | 1345970-00-4

• 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-(6-amino-2-hydrazinyl-9H-purin-9-yl)-5-(hydroxymethyl)-3-methyltetrahydrofuran-3,4-diol
• 英文别名: (2R,3R,4R,5R)-2-(6-amino-2-hydrazino-purin-9-yl)-5-(hydroxymethyl)-3-methyl-tetrahydrofuran-3,4-diol；(2R,3R,4R,5R)-2-(6-amino-2-hydrazinylpurin-9-yl)-5-(hydroxymethyl)-3-methyloxolane-3,4-diol
• CAS: 1345970-00-4
• 化学式: C₁₁H₁₇N₇O₄
• 分子量: 311.3
• InChiKey: ARNADOVVURXYMJ-GITKWUPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  178
• 氢给体数：
  6
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (2R,3R,4R,5R)-2-(6-amino-2-hydrazinyl-9H-purin-9-yl)-5-(hydroxymethyl)-3-methyltetrahydrofuran-3,4-diol 在 N-甲基咪唑 、 sodium nitrite 作用下， 以 四氢呋喃 、 水 、 溶剂黄146 、 乙腈 为溶剂， 反应 4.0h， 生成 ethyl ((((2R,3R,4R,5R)-5-(6-amino-2-azido-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：

  6-amino-2-chloro-9-(2-C-methyl-β-D-ribofuranosyl)-9H-purine 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 16.0h， 以92%的产率得到(2R,3R,4R,5R)-2-(6-amino-2-hydrazinyl-9H-purin-9-yl)-5-(hydroxymethyl)-3-methyltetrahydrofuran-3,4-diol
  参考文献：
  名称：

  合成嘌呤修饰的 2'-C-甲基核苷作为潜在的抗 HCV 药物

  摘要：

  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。

  DOI：

  10.1016/j.bmcl.2011.09.034

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.