2'-O-[2-(methylamino)-2-oxoethyl]-5-methyluridine | 815632-50-9

• 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 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 2'-O-[2-(methylamino)-2-oxoethyl]-5-methyluridine
• 英文别名: 2-[(2R,3R,4R,5R)-4-hydroxy-5-(hydroxymethyl)-2-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-N-methylacetamide
• CAS: 815632-50-9
• 化学式: C₁₃H₁₉N₃O₇
• 分子量: 329.31
• InChiKey: BGBZCAIQTSRSHI-UGKPPGOTSA-N

物化性质

• 熔点：
  193-194 °C(Solv: methanol (67-56-1))
• 密度：
  1.48±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  137
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2'-O-[2-(methylamino)-2-oxoethyl]-5-methyluridine 、 4,4'-双甲氧基三苯甲基氯 在 吡啶 作用下， 生成 5'-O-(4,4'-dimethoxytrityl)-2'-O-[2-(methylamino)-2-oxoethyl]-5-methyluridine
  参考文献：
  名称：

  Compounds and oligomeric compounds comprising novel nucleobases

  摘要：

  本发明涉及包含新型核碱基的核苷酸组合物以及包含至少一种此类核苷酸的寡聚合物化合物。这些寡聚合物化合物通常具有比没有这种修饰的寡聚合物化合物更强的结合亲和性能。这些寡聚合物化合物可用于调查和治疗等用途。

  公开号：

  US20040033973A1
• 作为产物：
  描述：

  2,2'-O-脱水-5-甲基尿嘧啶核苷 、 2-羟基-N-甲基乙酰胺 在 硼烷四氢呋喃络合物 、 碳酸氢钠 作用下， 150.0 ℃ 、758.44 kPa 条件下， 反应 48.08h， 以32%的产率得到2'-O-[2-(methylamino)-2-oxoethyl]-5-methyluridine
  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