ADD 219048 | 119689-60-0

• 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: ADD 219048
• 英文别名: 2-Methyl-3-phthalimidoanilin；N-(3-amino-2-methylphenyl)phthalimide；2-(3-amino-2-methylphenyl)isoindole-1,3-dione
• CAS: 119689-60-0
• 化学式: C₁₅H₁₂N₂O₂
• 分子量: 252.272
• InChiKey: JXDZXJZJLWROPY-UHFFFAOYSA-N

物化性质

• 熔点：
  230-232 °C(Solv: ethanol (64-17-5))
• 沸点：
  479.2±55.0 °C(Predicted)
• 密度：
  1.361±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  63.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ADD 219048 在 potassium carbonate 作用下， 以 various solvent(s) 为溶剂， 反应 3.67h， 生成 1-Ethyl-1,4-dihydro-8-methyl-7-phthalimido-4-oxo-chinolin-3-carbonsaeureethylester
  参考文献：
  名称：

  Synthesen neuer Chinolon-Chemotherapeutika, 1. Mitt.: Pyridochinoline und Pyridophenanthroline als ?lin-benzo-Nalidixins�ure?-Derivate

  摘要：

  DOI：

  10.1007/bf00809690
• 作为产物：
  描述：

  2-甲基-3-硝基苯胺 在 10percent Pd/C 溶剂黄146 、 环己烯 作用下， 以 异丙醇 为溶剂， 反应 5.0h， 生成 ADD 219048
  参考文献：
  名称：

  Synthesis and Anticonvulsant and Neurotoxic Properties of Substituted N-Phenyl Derivatives of the Phthalimide Pharmacophore

  摘要：

  A series of compounds including 4-amino (1), 3-amino (2), 4-nitro (3), 2-methyl-3-amino (4), 2-methyl-3-nitro (5), 2-methyl-4-amino (6), 2-methyl-4-nitro (7), 2-methyl-5-amino (8), 2-methyl-5-nitro (9), 2-methyl-6-amino (10), 2-methyl-6-nitro (11), 2,6-dimethyl (12), 2-methyl-3-carboxy (13), 2-methoxycarbonyl (14), 2-methyl-4-methoxy (15), 2,4-dimethoxy (16), 2-chloro-4-amino (17), and 2-chloro-4-nitro (18) N-phenyl substituents of phthalimide were evaluated along with N-[3-methyl-(2-pyridinyl)]phthalimide (19), N-(3-amino-2-methylphenyl)succinimide (20), and phenytoin for anticonvulsant and neurotoxic properties. Initial screening in the intraperitoneal tip) maximal electroshock-induced seizure (MES) test and the subcutaneous pentylenetetrazol-induced seizure (scPtz) test in mice led to the selection of 1, 2, 4, 10, 12, 17, and 19 for oral MES evaluation in rats. The resultant ED(50) values for 4, 10, 17, and phenytoin were 8.0, 28.3, 5.7 and 29.8 mg/kg, respectively. In the batrachotoxin affinity assay, IC(50) values for 17 and phenytoin were 0.15 and 0.93 mu M, respectively, and in the recently validated magnesium deficiency-dependent audiogenic seizure test, ED(50) values of 5.2 and 23 mg/kg were obtained for 17 and phenytoin, respectively. Electrophysiology studies on compound 17 point out its ability to (i) potentiate GABA-evoked current responses with a failure to directly activate the GABAA receptor and (ii) to affect, at 100 mu M excitatory non NMDA, but not NMDA, receptors with a 25% block of kainate-evoked response. Electrophysiology measurements on voltage-gated sodium channels in N1E-115 neuroblastoma cells confirm voltage-dependent block of these channels by compound 17. In view of its interaction with multiple ion channels, one would predict that compound 17 might be active in a wide range of seizure models.

  DOI：

  10.1021/jm990068t

文献信息

• Bourhim, Mustapha; Poupaert, Jacques H.; Stables, James P., Arzneimittel-Forschung/Drug Research, 1999, vol. 49, # 2, p. 81 - 87
  作者：Bourhim, Mustapha、Poupaert, Jacques H.、Stables, James P.、Vallee, Louis、Vamecq, Joseph

  DOI：——

  日期：——
• Anticonvulsant Activity of Some <i>N</i>-Phenylphthalimide Derivatives in Rats and Mice
  作者：Jacques H Poupaert、Gaëtane Hamoir、Philippe Barbeaux、Didier Lambert、Jean-Pierre Hénichart

  DOI：10.1111/j.2042-7158.1995.tb05741.x

  日期：2011.4.12
• JORDIS, U.;SAUTER, F.;RUDOLF, M.;CAI, GAN, MONATSH. CHEM., 119,(1988) N 6-7, 761-780
  作者：JORDIS, U.、SAUTER, F.、RUDOLF, M.、CAI, GAN

  DOI：——

  日期：——
• Synthesis and Anticonvulsant and Neurotoxic Properties of Substituted <i>N</i>-Phenyl Derivatives of the Phthalimide Pharmacophore
  作者：Joseph Vamecq、Pierre Bac、Christine Herrenknecht、Pierre Maurois、Philippe Delcourt、James P. Stables

  DOI：10.1021/jm990068t

  日期：2000.4.6

  A series of compounds including 4-amino (1), 3-amino (2), 4-nitro (3), 2-methyl-3-amino (4), 2-methyl-3-nitro (5), 2-methyl-4-amino (6), 2-methyl-4-nitro (7), 2-methyl-5-amino (8), 2-methyl-5-nitro (9), 2-methyl-6-amino (10), 2-methyl-6-nitro (11), 2,6-dimethyl (12), 2-methyl-3-carboxy (13), 2-methoxycarbonyl (14), 2-methyl-4-methoxy (15), 2,4-dimethoxy (16), 2-chloro-4-amino (17), and 2-chloro-4-nitro (18) N-phenyl substituents of phthalimide were evaluated along with N-[3-methyl-(2-pyridinyl)]phthalimide (19), N-(3-amino-2-methylphenyl)succinimide (20), and phenytoin for anticonvulsant and neurotoxic properties. Initial screening in the intraperitoneal tip) maximal electroshock-induced seizure (MES) test and the subcutaneous pentylenetetrazol-induced seizure (scPtz) test in mice led to the selection of 1, 2, 4, 10, 12, 17, and 19 for oral MES evaluation in rats. The resultant ED(50) values for 4, 10, 17, and phenytoin were 8.0, 28.3, 5.7 and 29.8 mg/kg, respectively. In the batrachotoxin affinity assay, IC(50) values for 17 and phenytoin were 0.15 and 0.93 mu M, respectively, and in the recently validated magnesium deficiency-dependent audiogenic seizure test, ED(50) values of 5.2 and 23 mg/kg were obtained for 17 and phenytoin, respectively. Electrophysiology studies on compound 17 point out its ability to (i) potentiate GABA-evoked current responses with a failure to directly activate the GABAA receptor and (ii) to affect, at 100 mu M excitatory non NMDA, but not NMDA, receptors with a 25% block of kainate-evoked response. Electrophysiology measurements on voltage-gated sodium channels in N1E-115 neuroblastoma cells confirm voltage-dependent block of these channels by compound 17. In view of its interaction with multiple ion channels, one would predict that compound 17 might be active in a wide range of seizure models.
• Synthesen neuer Chinolon-Chemotherapeutika, 1. Mitt.: Pyridochinoline und Pyridophenanthroline als ?lin-benzo-Nalidixins�ure?-Derivate
  作者：U. Jordis、F. Sauter、M. Rudolf、Gan Cai

  DOI：10.1007/bf00809690

  日期：——