4-Hydroxy-N-(2,6-dimethylphenyl)phthalimide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 4-Hydroxy-N-(2,6-dimethylphenyl)phthalimide
• 英文别名: 2-(2,6-dimethylphenyl)-5-hydroxyisoindole-1,3-dione
• 化学式: C₁₆H₁₃NO₃
• 分子量: 267.284
• InChiKey: GPUARNPEQNPVEX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-硝基邻苯二甲酸酐 在 palladium on activated charcoal 硫酸 、 溶剂黄146 、 环己烯 、 sodium nitrite 作用下， 以 异丙醇 为溶剂， 反应 9.5h， 生成 4-Hydroxy-N-(2,6-dimethylphenyl)phthalimide
  参考文献：
  名称：

  Anticonvulsant Activity and Interactions with Neuronal Voltage-Dependent Sodium Channel of Analogues of Ameltolide

  摘要：

  Fifteen compounds related to ameltolide (LY 201116) were studied for (i) anticonvulsant potential in the maximal electroshock-induced seizures (MES) and the subcutaneous pentylenetetrazol (sc Ptz) tests in mice and rats and (ii) interactions with neuronal voltage-dependent sodium channels. Compounds were chosen ranging in anticonvulsant activity in mice from very active to inactive. The active compounds were defined as those protecting 50% of the animals at doses between 10 and 50 mu mol/kg and inactive compounds as those protecting 50% of the animals at doses greater than 1 mmol/kg. The series studied included three N-(2,6-dimethylphenyl)benzamides (compounds 1, 2 (ameltolide), and 3), three N-(2,2,6,6-tetramethyl)piperidinyl-4-benzamides (compounds 4, 5, 6), one phenylthiourea (compound 7), five N-(2,6-dimethylphenyl)phthalimides (compounds 8, 9, 10, 13, and 14), two N-phenylphthalimide derivatives (compounds 11 and 12), and one N-(2,2,6,6-tetramethyl)piperidinyl-4-phtalimide (compound 15). Phenytoin (PHT) was employed as the reference prototype antiepileptic drug. After inital screening in mice, compounds 1, 2, 3, 5, 8, 9, 10, 13, and 14 were selected for further testing in rats. Anticonvulsant ED(50)s (effective doses in at least 50% of animals tested) of compounds in the MES test were determined in rats dosed orally and amounted to 52 (1), 135 (2), 284 (3), 31 (8), 131 (9), 25 (10), 369 (13), 354 (14), and 121 (PHT) mu mol/kg, compound 5 presenting with an ED50 value higher than 650 mu mol/kg. In our hands, the apparent IC(50)s (inhibitory concentrations 50) of compounds toward binding to rat brain synaptosomes of [H-3]batrachotoxinin-A-20 alpha-benzoate were 0.25 (1), 0.97 (2), 0.35 (3), 25.8 (5), 161.3 (8), 183.5 (9), 0.11 (10), 1.86 (13), 47.8 (14), and 0.86 (PHT) mu M. The relationship between the activity in the MES test and the capacity to interact in vitro with neuronal voltage-dependent sodium channels and the fact that the IC50 values obtained in the in vitro test are close to the brain concentrations at which anticonvulsant activities are reported to occur for ameltolide strongly suggest that the anticonvulsant properties of most compounds tested could be a direct result of their interaction with the neuronal voltage-dependent sodium channel.

  DOI：

  10.1021/jm9608772

文献信息

• Inhibitors of NF-κB derived from thalidomide
  作者：Esperanza J. Carcache de-Blanco、Bulbul Pandit、Zhigen Hu、Jiandong Shi、Andrew Lewis、Pui-Kai Li

  DOI：10.1016/j.bmcl.2007.01.088

  日期：2007.11

  A series of compounds originally derived from thalidomide were synthesized and evaluated. The most potent compounds in this series, 5HPP-33 and compound 20, inhibited NF-kappaB activation in HeLa cells. Preliminary study indicated that the mechanism of inhibition of NF-kappaB activation is through inhibition of its translocation from the cytoplasm to the nucleus.
• Anticonvulsant Activity and Interactions with Neuronal Voltage-Dependent Sodium Channel of Analogues of Ameltolide
  作者：Joseph Vamecq、Didier Lambert、Jacques H. Poupaert、Bernard Masereel、James P. Stables

  DOI：10.1021/jm9608772

  日期：1998.8.1

  Fifteen compounds related to ameltolide (LY 201116) were studied for (i) anticonvulsant potential in the maximal electroshock-induced seizures (MES) and the subcutaneous pentylenetetrazol (sc Ptz) tests in mice and rats and (ii) interactions with neuronal voltage-dependent sodium channels. Compounds were chosen ranging in anticonvulsant activity in mice from very active to inactive. The active compounds were defined as those protecting 50% of the animals at doses between 10 and 50 mu mol/kg and inactive compounds as those protecting 50% of the animals at doses greater than 1 mmol/kg. The series studied included three N-(2,6-dimethylphenyl)benzamides (compounds 1, 2 (ameltolide), and 3), three N-(2,2,6,6-tetramethyl)piperidinyl-4-benzamides (compounds 4, 5, 6), one phenylthiourea (compound 7), five N-(2,6-dimethylphenyl)phthalimides (compounds 8, 9, 10, 13, and 14), two N-phenylphthalimide derivatives (compounds 11 and 12), and one N-(2,2,6,6-tetramethyl)piperidinyl-4-phtalimide (compound 15). Phenytoin (PHT) was employed as the reference prototype antiepileptic drug. After inital screening in mice, compounds 1, 2, 3, 5, 8, 9, 10, 13, and 14 were selected for further testing in rats. Anticonvulsant ED(50)s (effective doses in at least 50% of animals tested) of compounds in the MES test were determined in rats dosed orally and amounted to 52 (1), 135 (2), 284 (3), 31 (8), 131 (9), 25 (10), 369 (13), 354 (14), and 121 (PHT) mu mol/kg, compound 5 presenting with an ED50 value higher than 650 mu mol/kg. In our hands, the apparent IC(50)s (inhibitory concentrations 50) of compounds toward binding to rat brain synaptosomes of [H-3]batrachotoxinin-A-20 alpha-benzoate were 0.25 (1), 0.97 (2), 0.35 (3), 25.8 (5), 161.3 (8), 183.5 (9), 0.11 (10), 1.86 (13), 47.8 (14), and 0.86 (PHT) mu M. The relationship between the activity in the MES test and the capacity to interact in vitro with neuronal voltage-dependent sodium channels and the fact that the IC50 values obtained in the in vitro test are close to the brain concentrations at which anticonvulsant activities are reported to occur for ameltolide strongly suggest that the anticonvulsant properties of most compounds tested could be a direct result of their interaction with the neuronal voltage-dependent sodium channel.