4-N-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-O-[2-(methylamino)-2-oxoethyl]-5-methylcytidine | 1025783-19-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 4-N-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-O-[2-(methylamino)-2-oxoethyl]-5-methylcytidine
• CAS: 1025783-19-0
• 化学式: C₄₁H₄₂N₄O₉
• 分子量: 734.806
• InChiKey: YBSRZHFNUAMLRB-ZENBVRMOSA-N

物化性质

• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.22
• 重原子数：
  54.0
• 可旋转键数：
  14.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  159.47
• 氢给体数：
  3.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  丁二酸酐 、 4-N-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-O-[2-(methylamino)-2-oxoethyl]-5-methylcytidine 在 4-二甲氨基吡啶 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以71%的产率得到4-N-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-O-[2-(methylamino)-2-oxoethyl]-5-methylcytidine 3'-O-succinate
  参考文献：
  名称：

  Comparing In Vitro and In Vivo Activity of 2′-O-[2-(Methylamino)-2-oxoethyl]- and 2′-O-Methoxyethyl-Modified Antisense Oligonucleotides

  摘要：

  A number of 2'-O-modified antisense oligonucleotides have been reported for their potential use in oligonucleotide-based therapeutics. To date, most of the in vivo data has been generated for 2'-O-MOE (2'-O-methoxyethyl)- and 2'-O-Me (2'-O-methyl)-modified ASOs (antisense oligonucleotides). We now report the synthesis and biological activity of another 2'-O-modification, namely 2'-O-[2-(methylamino)-2-oxoethyl] (2'-O-NMA). This modification resulted in an increase in the affinity of antisense oligonucleotides to complementary RNA similar to 2'-O-MOE-modified ASOs as compared to first-generation antisense oligodeoxynucleotides. The ASO modified with 2'-O-NMA reduced expression of PTEN mRNA in vitro and in vivo in a dose-dependent manner similar to 2'-O-MOE modified ASO. Importantly, toxicity parameters such as AST, ALT, organ weights, and body weights were found to be normal similar to 2'-O-MOE ASO-treated animal models. The data generated in these experiments suggest that 2'-O-NMA is a useful modification for potential application in both antisense and other oligonucleotide-based drug discovery efforts.

  DOI：

  10.1021/jm701537z
• 作为产物：
  描述：

  5'-O-(4,4'-dimethoxytrityl)-2'-O-[2-(methylamino)-2-oxoethyl]-5-methylcytidine 、 苯甲酸酐 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 以89.4%的产率得到4-N-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-O-[2-(methylamino)-2-oxoethyl]-5-methylcytidine
  参考文献：
  名称：

  Comparing In Vitro and In Vivo Activity of 2′-O-[2-(Methylamino)-2-oxoethyl]- and 2′-O-Methoxyethyl-Modified Antisense Oligonucleotides

  摘要：

  A number of 2'-O-modified antisense oligonucleotides have been reported for their potential use in oligonucleotide-based therapeutics. To date, most of the in vivo data has been generated for 2'-O-MOE (2'-O-methoxyethyl)- and 2'-O-Me (2'-O-methyl)-modified ASOs (antisense oligonucleotides). We now report the synthesis and biological activity of another 2'-O-modification, namely 2'-O-[2-(methylamino)-2-oxoethyl] (2'-O-NMA). This modification resulted in an increase in the affinity of antisense oligonucleotides to complementary RNA similar to 2'-O-MOE-modified ASOs as compared to first-generation antisense oligodeoxynucleotides. The ASO modified with 2'-O-NMA reduced expression of PTEN mRNA in vitro and in vivo in a dose-dependent manner similar to 2'-O-MOE modified ASO. Importantly, toxicity parameters such as AST, ALT, organ weights, and body weights were found to be normal similar to 2'-O-MOE ASO-treated animal models. The data generated in these experiments suggest that 2'-O-NMA is a useful modification for potential application in both antisense and other oligonucleotide-based drug discovery efforts.

  DOI：

  10.1021/jm701537z