2’-deoxy-2’,2’-difluoro-1’-[(2-amino-imidazo-[4’,5’:4,5]-thieno-[3,2-d]pyrimidin-3-yl-7-one)]-β-D-ribofuranose

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: 2’-deoxy-2’,2’-difluoro-1’-[(2-amino-imidazo-[4’,5’:4,5]-thieno-[3,2-d]pyrimidin-3-yl-7-one)]-β-D-ribofuranose
• 英文别名: 11-amino-3-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-thia-3,5,10,12-tetrazatricyclo[6.4.0.02,6]dodeca-1(8),2(6),4,11-tetraen-9-one
• 化学式: C₁₂H₁₁F₂N₅O₄S
• 分子量: 359.313
• InChiKey: HHZDMVISZFWVBQ-FJRWEMQYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  163
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  索非布韦中间体 、 2’-deoxy-2’,2’-difluoro-1’-[(2-amino-imidazo-[4’,5’:4,5]-thieno-[3,2-d]pyrimidin-3-yl-7-one)]-β-D-ribofuranose 在 叔丁基氯化镁 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 propan-2-yl (2S)-2-[[[(2R,3R,5R)-5-(11-amino-9-oxo-7-thia-3,5,10,12-tetrazatricyclo[6.4.0.02,6]dodeca-1(8),2(6),4,11-tetraen-3-yl)-4,4-difluoro-3-hydroxyoxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate 、 propan-2-yl (2S)-2-[[[(2R,3R,5R)-5-(11-amino-9-oxo-7-thia-3,5,10,12-tetrazatricyclo[6.4.0.02,6]dodeca-1(8),2(6),4,11-tetraen-3-yl)-4,4-difluoro-3-[[[(2S)-1-oxo-1-propan-2-yloxypropan-2-yl]amino]-phenoxyphosphoryl]oxyoxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate
  参考文献：
  名称：

  Thiophene-expanded guanosine analogues of Gemcitabine

  摘要：

  The chemotherapeutic drug Gemcitabine, 2',2'-difluoro-2'-deoxycytidine, has long been the standard of care for a number of cancers. Gemcitabine's chemotherapeutic properties stem from its 2',2'-difluoro-2'- deoxyribose sugar, which mimics the natural nucleoside, but also disrupts nucleic acid synthesis, leading to cell death. As a result, numerous analogues have been prepared to further explore the biological implications for this structural modification. In that regard, a thieno-expanded guanosine analogue was of interest due to biological activity previously observed for the tricyclic heterobase scaffold. Several analogues were prepared, including the McGuigan ProTide, however the parent nucleoside exhibited the best chemotherapeutic activity, specifically against breast cancer cell lines (89.53% growth inhibition). (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.07.086
• 作为产物：
  描述：

  2-deoxy-2,2-difluoro-1-oxoribose 在 吡啶 、 偶氮二甲酸二异丙酯 、 三氟化硼乙醚 、 乙基溴化镁 、 盐酸羟胺 、 sodium methylate 、 sodium ethanolate 、 C₁₃H₂₈AlLiO₃ 、 sodium hydride 、 碳酸氢钠 、 potassium carbonate 、 三苯基膦 、 N,N'-羰基二咪唑 、 乙硫醇 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 179.17h， 生成 2’-deoxy-2’,2’-difluoro-1’-[(2-amino-imidazo-[4’,5’:4,5]-thieno-[3,2-d]pyrimidin-3-yl-7-one)]-β-D-ribofuranose
  参考文献：
  名称：

  Thiophene-expanded guanosine analogues of Gemcitabine

  摘要：

  The chemotherapeutic drug Gemcitabine, 2',2'-difluoro-2'-deoxycytidine, has long been the standard of care for a number of cancers. Gemcitabine's chemotherapeutic properties stem from its 2',2'-difluoro-2'- deoxyribose sugar, which mimics the natural nucleoside, but also disrupts nucleic acid synthesis, leading to cell death. As a result, numerous analogues have been prepared to further explore the biological implications for this structural modification. In that regard, a thieno-expanded guanosine analogue was of interest due to biological activity previously observed for the tricyclic heterobase scaffold. Several analogues were prepared, including the McGuigan ProTide, however the parent nucleoside exhibited the best chemotherapeutic activity, specifically against breast cancer cell lines (89.53% growth inhibition). (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.07.086