(E)-4-oxo-4-[2-[5-(2-phenoxyphenyl)pyridine-2-carbonyl]hydrazinyl]but-2-enoic acid | 1431771-42-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (E)-4-oxo-4-[2-[5-(2-phenoxyphenyl)pyridine-2-carbonyl]hydrazinyl]but-2-enoic acid
• CAS: 1431771-42-4
• 化学式: C₂₂H₁₇N₃O₅
• 分子量: 403.394
• InChiKey: URMGHYFSSJBWJE-OUKQBFOZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  118
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-溴吡啶-2-羧酸甲酯 在 四(三苯基膦)钯 、 lithium hydroxide monohydrate 、 sodium carbonate 、 一水合肼 作用下， 以 四氢呋喃 、 甲醇 、 水 、 乙酸乙酯 为溶剂， 反应 26.0h， 生成 (E)-4-oxo-4-[2-[5-(2-phenoxyphenyl)pyridine-2-carbonyl]hydrazinyl]but-2-enoic acid
  参考文献：
  名称：

  Structural Basis for Inhibition of the Fat Mass and Obesity Associated Protein (FTO)

  摘要：

  The fat mass and obesity associated protein (FTO) is a potential target for anti-obesity medicines. FTO is a 2-oxoglutarate (2OG)-dependent N-methyl nucleic acid demethylase that acts on substrates including 3-methylthymidine, 3-methyluracil, and 6-methyladenine. To identify FTO inhibitors, we screened a set of 2OG analogues and related compounds using differential scanning fluorometry- and liquid chromatography-based assays. The results revealed sets of both cyclic and acyclic 2OG analogues that are FTO inhibitors. Identified inhibitors include small molecules that have been used in clinical studies for the inhibition of other 2OG oxygenases. Crystallo-graphic analyses reveal inhibition by 2OG cosubstrate or primary substrate competitors as well as compounds that bind across both cosubstrate and primary substrate binding sites. The results will aid the development of more potent and selective FTO inhibitors.

  DOI：

  10.1021/jm400193d

文献信息

• Structural Basis for Inhibition of the Fat Mass and Obesity Associated Protein (FTO)
  作者：WeiShen Aik、Marina Demetriades、Muhammad K. K. Hamdan、Eleanor. A. L. Bagg、Kar Kheng Yeoh、Clarisse Lejeune、Zhihong Zhang、Michael A. McDonough、Christopher J. Schofield

  DOI：10.1021/jm400193d

  日期：2013.5.9

  The fat mass and obesity associated protein (FTO) is a potential target for anti-obesity medicines. FTO is a 2-oxoglutarate (2OG)-dependent N-methyl nucleic acid demethylase that acts on substrates including 3-methylthymidine, 3-methyluracil, and 6-methyladenine. To identify FTO inhibitors, we screened a set of 2OG analogues and related compounds using differential scanning fluorometry- and liquid chromatography-based assays. The results revealed sets of both cyclic and acyclic 2OG analogues that are FTO inhibitors. Identified inhibitors include small molecules that have been used in clinical studies for the inhibition of other 2OG oxygenases. Crystallo-graphic analyses reveal inhibition by 2OG cosubstrate or primary substrate competitors as well as compounds that bind across both cosubstrate and primary substrate binding sites. The results will aid the development of more potent and selective FTO inhibitors.