[6-N-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-O-[2-(methylamino)-2-oxoethyl]adenosine]-3'-[(2-cyanoethyl)-N,N-diisopropyl]phosphoramidite | 1025783-20-3

• 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: [6-N-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-O-[2-(methylamino)-2-oxoethyl]adenosine]-3'-[(2-cyanoethyl)-N,N-diisopropyl]phosphoramidite
• 英文别名: (2R,3R,4R,5R)-5-(6-Benzamido-9H-purin-9-yl)-2-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-4-(2-(methylamino)-2-oxoethoxy)tetrahydrofuran-3-yl (2-cyanoethyl) diisopropylphosphoramidite；N-[9-[(2R,3R,4R,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-[2-cyanoethoxy-[di(propan-2-yl)amino]phosphanyl]oxy-3-[2-(methylamino)-2-oxoethoxy]oxolan-2-yl]purin-6-yl]benzamide
• CAS: 1025783-20-3
• 化学式: C₅₀H₅₇N₈O₉P
• 分子量: 945.025
• InChiKey: GEYNOJIHDLPUEX-GNUXOQNYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.79
• 重原子数：
  68.0
• 可旋转键数：
  22.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  193.44
• 氢给体数：
  2.0
• 氢受体数：
  15.0

反应信息

• 作为产物：
  描述：

  6-N-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-O-[2-(methylamino)-2-oxoethyl]adenosine 、 双(二异丙基氨基)(2-氰基乙氧基)膦 在 二异丙基铵盐四氮唑 作用下， 以 乙腈 为溶剂， 反应 10.0h， 以70%的产率得到[6-N-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-O-[2-(methylamino)-2-oxoethyl]adenosine]-3'-[(2-cyanoethyl)-N,N-diisopropyl]phosphoramidite
  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