(R)-methyl 2-([2,2'-bipyridine]-6-carboxamido)-3-((naphthalen-2-ylmethyl)thio)propanoate | 1361296-51-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R)-methyl 2-([2,2'-bipyridine]-6-carboxamido)-3-((naphthalen-2-ylmethyl)thio)propanoate
• CAS: 1361296-51-6
• 化学式: C₂₆H₂₃N₃O₃S
• 分子量: 457.553
• InChiKey: VNJVXVLGQOQVFS-DEOSSOPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  33.0
• 可旋转键数：
  8.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  81.18
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (R)-methyl 2-([2,2'-bipyridine]-6-carboxamido)-3-((naphthalen-2-ylmethyl)thio)propanoate 在 lithium hydroxide 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 24.0h， 以65%的产率得到(R)-2-([2,2'-bipyridine]-6-carboxamido)-3-((naphthalen-2-ylmethyl)thio)propanoic acid
  参考文献：
  名称：

  Dynamic Combinatorial Mass Spectrometry Leads to Inhibitors of a 2-Oxoglutarate-Dependent Nucleic Acid Demethylase

  摘要：

  2-Oxoglutarate-dependent nucleic acid demethylases are of biological interest because of their roles in nucleic acid repair and modification. Although some of these enzymes are linked to physiology, their regulatory roles are unclear. Hence, there is a desire to develop selective inhibitors for them; we report studies on AlkB, which reveal it as being amenable to selective inhibition by small molecules. Dynamic combinatorial chemistry linked to mass spectrometric analyses (DCMS) led to the identification of lead compounds, one of which was analyzed by crystallography. Subsequent structure-guided studies led to the identification of inhibitors of improved potency, some of which were shown to be selective over two other 2OG oxygenases. The work further validates the use of the DCMS method and will help to enable the development of inhibitors of nucleic acid modifying 2OG oxygenases both for use as functional probes and, in the longer term, for potential therapeutic use.

  DOI：

  10.1021/jm201417e
• 作为产物：
  描述：

  2-溴甲基萘 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 120.0h， 生成 (R)-methyl 2-([2,2'-bipyridine]-6-carboxamido)-3-((naphthalen-2-ylmethyl)thio)propanoate
  参考文献：
  名称：

  Dynamic Combinatorial Mass Spectrometry Leads to Inhibitors of a 2-Oxoglutarate-Dependent Nucleic Acid Demethylase

  摘要：

  2-Oxoglutarate-dependent nucleic acid demethylases are of biological interest because of their roles in nucleic acid repair and modification. Although some of these enzymes are linked to physiology, their regulatory roles are unclear. Hence, there is a desire to develop selective inhibitors for them; we report studies on AlkB, which reveal it as being amenable to selective inhibition by small molecules. Dynamic combinatorial chemistry linked to mass spectrometric analyses (DCMS) led to the identification of lead compounds, one of which was analyzed by crystallography. Subsequent structure-guided studies led to the identification of inhibitors of improved potency, some of which were shown to be selective over two other 2OG oxygenases. The work further validates the use of the DCMS method and will help to enable the development of inhibitors of nucleic acid modifying 2OG oxygenases both for use as functional probes and, in the longer term, for potential therapeutic use.

  DOI：

  10.1021/jm201417e