6-N-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-O-[2-(methylamino)-2-oxoethyl]adenosine | 1025783-21-4

• 物质功能分类: 医药中间体 - 原料药中间体
• 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
• 英文别名: N-(9-((2R,3R,4R,5R)-5-((Bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-4-hydroxy-3-(2-(methylamino)-2-oxoethoxy)tetrahydrofuran-2-yl)-9H-purin-6-yl)benzamide；N-[9-[(2R,3R,4R,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-hydroxy-3-[2-(methylamino)-2-oxoethoxy]oxolan-2-yl]purin-6-yl]benzamide
• CAS: 1025783-21-4
• 化学式: C₄₁H₄₀N₆O₈
• 分子量: 744.804
• InChiKey: UAAMRXVSAVCRLX-CKODAUBMSA-N

物化性质

• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.49
• 重原子数：
  55.0
• 可旋转键数：
  14.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  168.18
• 氢给体数：
  3.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  丁二酸酐 、 6-N-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-O-[2-(methylamino)-2-oxoethyl]adenosine 在 4-二甲氨基吡啶 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以98%的产率得到6-N-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-O-[2-(methylamino)-2-oxoethyl]adenosine 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：

  6-N-benzoyl-2'-O-[2-(methylamino)-2-oxoethyl]adenosine 、 4,4'-双甲氧基三苯甲基氯 在 吡啶 作用下， 反应 10.0h， 以65%的产率得到6-N-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-O-[2-(methylamino)-2-oxoethyl]adenosine
  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