[(3R,4S,5S)-2-acetyloxy-5-[(methylideneamino)oxymethyl]-4-(naphthalen-2-ylmethoxy)-5-(naphthalen-2-ylmethoxymethyl)oxolan-3-yl] acetate | 1207867-60-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: [(3R,4S,5S)-2-acetyloxy-5-[(methylideneamino)oxymethyl]-4-(naphthalen-2-ylmethoxy)-5-(naphthalen-2-ylmethoxymethyl)oxolan-3-yl] acetate
• CAS: 1207867-60-4
• 化学式: C₃₃H₃₃NO₈
• 分子量: 571.627
• InChiKey: XNQQJPZJXFGGJP-DYRNCJCTSA-N

物化性质

• 沸点：
  699.9±65.0 °C(predicted)
• 密度：
  1.23±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  42
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  102
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  [(3R,4S,5S)-2-acetyloxy-5-[(methylideneamino)oxymethyl]-4-(naphthalen-2-ylmethoxy)-5-(naphthalen-2-ylmethoxymethyl)oxolan-3-yl] acetate 、 尿嘧啶 在 N,O-双三甲硅基乙酰胺 、 三氟甲磺酸三甲基硅酯 作用下， 以 乙腈 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  Antisense Oligonucleotides Containing Conformationally Constrained 2′,4′-(N-Methoxy)aminomethylene and 2′,4′-Aminooxymethylene and 2′-O,4′-C-Aminomethylene Bridged Nucleoside Analogues Show Improved Potency in Animal Models

  摘要：

  To identify chemistries and strategies to improve the potency of MOE second generation ASOs, we have evaluated gapmer antisense oligonucleotides containing BNAs having N-O bonds. These modifications include N-MeO-amino BNA, N-Me-aminooxy BNA, 2'4'-BNA(NC)[NMe], and 2',4'-BNA(NC) bridged nucleoside analogues. These modifications provided increased thermal stability and improved in vitro activity compared to the corresponding ASO containing the MOE modification. Additionally, ASOs containing N-MeO-amino BNA, N-Me-aminooxy BNA, and 2',4'-BNA(NC)[NMe] modifications showed improved in vivo activity (> 5-fold) compared to MOE ASO. Importantly, toxicity parameters, such as AST, ALT, liver, kidney, and body weights, were found to be normal for N-MeO-amino BNA, N-Me-aminooxy BNA, and 2'4'-BNA(NC)[NMe] ASO treated animals. The data generated in these experiments suggest that N-MeO-amino BNA, N-Me-aminooxy BNA, and 2'4'-BNA(NC)[NMe] are useful modifications for applications in both antisense and other oligonucleotide based drug discovery efforts.

  DOI：

  10.1021/jm9013295
• 作为产物：
  描述：

  N-[[(3aR,5S,6S,6aR)-2,2-dimethyl-6-(naphthalen-2-ylmethoxy)-5-(naphthalen-2-ylmethoxymethyl)-6,6a-dihydro-3aH-furo[2,3-d][1,3]dioxol-5-yl]methoxy]methanimine 、 乙酸酐 在 吡啶 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 75.0h， 以75%的产率得到[(3R,4S,5S)-2-acetyloxy-5-[(methylideneamino)oxymethyl]-4-(naphthalen-2-ylmethoxy)-5-(naphthalen-2-ylmethoxymethyl)oxolan-3-yl] acetate
  参考文献：
  名称：

  Antisense Oligonucleotides Containing Conformationally Constrained 2′,4′-(N-Methoxy)aminomethylene and 2′,4′-Aminooxymethylene and 2′-O,4′-C-Aminomethylene Bridged Nucleoside Analogues Show Improved Potency in Animal Models

  摘要：

  To identify chemistries and strategies to improve the potency of MOE second generation ASOs, we have evaluated gapmer antisense oligonucleotides containing BNAs having N-O bonds. These modifications include N-MeO-amino BNA, N-Me-aminooxy BNA, 2'4'-BNA(NC)[NMe], and 2',4'-BNA(NC) bridged nucleoside analogues. These modifications provided increased thermal stability and improved in vitro activity compared to the corresponding ASO containing the MOE modification. Additionally, ASOs containing N-MeO-amino BNA, N-Me-aminooxy BNA, and 2',4'-BNA(NC)[NMe] modifications showed improved in vivo activity (> 5-fold) compared to MOE ASO. Importantly, toxicity parameters, such as AST, ALT, liver, kidney, and body weights, were found to be normal for N-MeO-amino BNA, N-Me-aminooxy BNA, and 2'4'-BNA(NC)[NMe] ASO treated animals. The data generated in these experiments suggest that N-MeO-amino BNA, N-Me-aminooxy BNA, and 2'4'-BNA(NC)[NMe] are useful modifications for applications in both antisense and other oligonucleotide based drug discovery efforts.

  DOI：

  10.1021/jm9013295