1-(4-Hydroxy-3-methoxy-5-nitro-phenyl)-3-phenyl-propan-1-one | 400871-00-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 1-(4-Hydroxy-3-methoxy-5-nitro-phenyl)-3-phenyl-propan-1-one
• 英文别名: 1-(4-Hydroxy-3-methoxy-5-nitrophenyl)-3-phenylpropan-1-one
• CAS: 400871-00-3
• 化学式: C₁₆H₁₅NO₅
• 分子量: 301.299
• InChiKey: KTSLOQBIIBFFEZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  92.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(4-Hydroxy-3-methoxy-5-nitro-phenyl)-3-phenyl-propan-1-one 在 吡啶 、 三氯化铝 作用下， 以 乙酸乙酯 为溶剂， 反应 2.0h， 生成 1-(3,4-Dihydroxy-5-nitro-phenyl)-3-phenyl-propan-1-one
  参考文献：
  名称：

  Synthesis of 1-(3,4-Dihydroxy-5-nitrophenyl)-2-phenyl-ethanone and Derivatives as Potent and Long-Acting Peripheral Inhibitors of Catechol-O-methyltransferase

  摘要：

  A homologous series of novel nitro-catechol structures (7a-7e) were synthesized and tested as inhibitors of the enzyme catechol-O-methyltransferase (COMT). Increasing chain length was found to have significant impact on both brain penetration and duration of COMT inhibition in the rat. Of this series, compound 7b (1-(3,4-dihydroxy-5-nitrophenyl)-2-phenyl-ethanone) was found to exhibit the most potent and selective inhibition of peripheral COMT, with an inhibition profile more similar to entacapone 2 than tolcapone 1 (an equipotent peripheral and central inhibitor) but with much improved duration of action (7b, 70% inhibition and 2, 25% inhibition at 9 h after administration). The effects of structural modifications to 7b on COMT inhibitory profile were investigated, and it is concluded that the carbonyl group and preferably unsubstituted aromatic ring are essential features to maintain prolonged peripheral COMT inhibition. The introduction of the alpha-methylene group, the major structural difference between 7b and 1, would appear responsible for the observed enhancement in selectivity of peripheral COMT inhibition of 7b, which has more limited access to the brain than 1.

  DOI：

  10.1021/jm0109964
• 作为产物：
  描述：

  1-(4-hydroxy-3-methoxyphenyl)-3-phenylpropan-1-one 在 溶剂黄146 作用下， 反应 0.5h， 以71%的产率得到1-(4-Hydroxy-3-methoxy-5-nitro-phenyl)-3-phenyl-propan-1-one
  参考文献：
  名称：

  Synthesis of 1-(3,4-Dihydroxy-5-nitrophenyl)-2-phenyl-ethanone and Derivatives as Potent and Long-Acting Peripheral Inhibitors of Catechol-O-methyltransferase

  摘要：

  A homologous series of novel nitro-catechol structures (7a-7e) were synthesized and tested as inhibitors of the enzyme catechol-O-methyltransferase (COMT). Increasing chain length was found to have significant impact on both brain penetration and duration of COMT inhibition in the rat. Of this series, compound 7b (1-(3,4-dihydroxy-5-nitrophenyl)-2-phenyl-ethanone) was found to exhibit the most potent and selective inhibition of peripheral COMT, with an inhibition profile more similar to entacapone 2 than tolcapone 1 (an equipotent peripheral and central inhibitor) but with much improved duration of action (7b, 70% inhibition and 2, 25% inhibition at 9 h after administration). The effects of structural modifications to 7b on COMT inhibitory profile were investigated, and it is concluded that the carbonyl group and preferably unsubstituted aromatic ring are essential features to maintain prolonged peripheral COMT inhibition. The introduction of the alpha-methylene group, the major structural difference between 7b and 1, would appear responsible for the observed enhancement in selectivity of peripheral COMT inhibition of 7b, which has more limited access to the brain than 1.

  DOI：

  10.1021/jm0109964