2-amino-N6-methyl-N6-methylsulfonamido-9-(2'β-methyl-β-D-ribofuranosyl)adenine | 914912-04-2

• 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: 2-amino-N6-methyl-N6-methylsulfonamido-9-(2'β-methyl-β-D-ribofuranosyl)adenine
• 英文别名: 2-amino-6-(1-methyl-2-methylsulfonylhydrazino)-9-(2'-methyl-β-D-ribofuranosyl)purine；N'-[2-amino-9-[(2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]purin-6-yl]-N'-methylmethanesulfonohydrazide
• CAS: 914912-04-2
• 化学式: C₁₃H₂₁N₇O₆S
• 分子量: 403.419
• InChiKey: YQEKFWLTECKRNP-VHQAPHLWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  197
• 氢给体数：
  5
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  2-amino-N6-methyl-N6-methylsulfonamido-9-(2'β-methyl-β-D-ribofuranosyl)adenine 在 phosphorus pentoxide 、 三氯氧磷 、 氢氧化钾 作用下， 以 磷酸三甲酯 、 水 、 乙腈 为溶剂， 反应 6.42h， 生成 N'-(2-amino-9-((4aR,6R,7R,7aR)-2,7-dihydroxy-7-methyl-2-oxidotetrahydro-4H-furo[3,2-d][1,3,2]dioxaphosphinin-6-yl)-9H-purin-6-yl)-N'-methylmethanesulfonohydrazide
  参考文献：
  名称：

  WO2007/27248

  摘要：

  公开号：
• 作为产物：
  描述：

  2-amino-6-(1-methylhydrazino)-9-(2',3',5'-tri-O-benzoyl-2'-methyl-β-D-ribofuranosyl)purine 在 TEA 、 氨 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 26.0h， 生成 2-amino-N6-methyl-N6-methylsulfonamido-9-(2'β-methyl-β-D-ribofuranosyl)adenine
  参考文献：
  名称：

  6-Hydrazinopurine 2′-methyl ribonucleosides and their 5′-monophosphate prodrugs as potent hepatitis C virus inhibitors

  摘要：

  A series of 6-hydrazinopurine 2 '-methyl ribonucleosides was synthesized and tested for its inhibitory activity against the hepatitis C virus (HCV). The lack of antiviral activity of these nucleosides was associated with a poor affinity for adenosine kinase, which prompted us to synthesize several of their 5 '-monophosphate prodrugs. Some of these prodrugs exhibited more than 1000-fold improvement in anti-HCV activity when compared to their parent nucleosides (EC50 of 24 mu M vs 92 mu M for the parent). (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.02.029

文献信息

• WO2007/27248
  申请人：——

  公开号：——

  公开（公告）日：——
• WO2006/121820
  申请人：——

  公开号：——

  公开（公告）日：——
• WO2006/122207
  申请人：——

  公开号：——

  公开（公告）日：——
• 6-Hydrazinopurine 2′-methyl ribonucleosides and their 5′-monophosphate prodrugs as potent hepatitis C virus inhibitors
  作者：Esmir Gunic、Suetying Chow、Frank Rong、Kanda Ramasamy、Anneke Raney、David Yunzhi Li、Jingfan Huang、Robert K. Hamatake、Zhi Hong、Jean-Luc Girardet

  DOI：10.1016/j.bmcl.2007.02.029

  日期：2007.5

  A series of 6-hydrazinopurine 2 '-methyl ribonucleosides was synthesized and tested for its inhibitory activity against the hepatitis C virus (HCV). The lack of antiviral activity of these nucleosides was associated with a poor affinity for adenosine kinase, which prompted us to synthesize several of their 5 '-monophosphate prodrugs. Some of these prodrugs exhibited more than 1000-fold improvement in anti-HCV activity when compared to their parent nucleosides (EC50 of 24 mu M vs 92 mu M for the parent). (C) 2007 Elsevier Ltd. All rights reserved.
• Cyclic monophosphate prodrugs of base-modified 2′-C-methyl ribonucleosides as potent inhibitors of hepatitis C virus RNA replication
  作者：Esmir Gunic、Jean-Luc Girardet、Kanda Ramasamy、Vesna Stoisavljevic-Petkov、Suetying Chow、Li-Tain Yeh、Robert K. Hamatake、Anneke Raney、Zhi Hong

  DOI：10.1016/j.bmcl.2007.02.030

  日期：2007.5

  A new series of heterobase-modified 2 '-C-methyl ribonucleosides was synthesized and tested as inhibitors of hepatitis C virus (HCV) RNA replication. The nucleosides showed a weak inhibitory activity in a HCV replicon system (EC50 = 92 mu M) and did not exhibit any cytotoxicity (CC50 > 300 mu M). Cyclic monophosphate (cMP) prodrugs of the same nucleosides were synthesized and also tested in the HCV replicon system. Prodrugs exhibited strong potency (EC50 = 0-008)mu M) without significant cytotoxicity (CC50 > 50 mu M). (C) 2007 Elsevier Ltd. All rights reserved.