1-acetyl-4-(4-fluorophenyl)-3-morpholinopyrrole-2-carboxylic acid methyl ester

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 1-acetyl-4-(4-fluorophenyl)-3-morpholinopyrrole-2-carboxylic acid methyl ester
• 英文别名: N-Acetyl-4-(4-fluorophenyl)-3-morpholinopyrrol-2-carboxylic acid, methyl ester；methyl 1-acetyl-4-(4-fluorophenyl)-3-morpholin-4-ylpyrrole-2-carboxylate
• 化学式: C₁₈H₁₉FN₂O₄
• 分子量: 346.358
• InChiKey: MDMPIWRFGDCDSO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  60.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-(4-Fluoro-phenyl)-3-morpholin-4-yl-1H-pyrrole-2-carboxylic acid methyl ester 、 alkaline earth salt of/the/ methylsulfuric acid 在 sodium hydride 作用下， 生成 1-acetyl-4-(4-fluorophenyl)-3-morpholinopyrrole-2-carboxylic acid methyl ester
  参考文献：
  名称：

  Synthesis, Anticonvulsant Activity, and Structure−Activity Relationships of Sodium Channel Blocking 3-Aminopyrroles

  摘要：

  Starting from the corresponding acetophenone and glycine derivatives, a series of new 3-aminopyrroles was synthesized in few steps. Using this procedure with hydrazine and hydroxylamine instead of the glycinates provides access to S-aminopyrazoles and 5-amino-1,2-oxazoles. The various derivatives were tested for anticonvulsant activity in a variety of test models. Several compounds exhibit considerable activity with a remarkable lack of neurotoxicity. 4-(4-Bromophenyl)-3-morpholinopyrrole-2-carboxylic acid methyl ester, 3, proved to be the most active compound. It was protective in the maximal electroshock seizure (MES) test in rats with an oral ED50 of 2.5 mg/kg with no neurotoxicity noted at doses up to 500 mg/kg. Compound 3 blocks sodium channels in a frequency-dependent manner. The essential structural features which could be responsible for an interaction with an active site of the voltage-dependent sodium channel are established within a suggested pharmacophore model.

  DOI：

  10.1021/jm970327j

文献信息

• Synthesis, Anticonvulsant Activity, and Structure−Activity Relationships of Sodium Channel Blocking 3-Aminopyrroles
  作者：Klaus Unverferth、Jürgen Engel、Norbert Höfgen、Angelika Rostock、Ralf Günther、Hans-Joachim Lankau、Manfred Menzer、Andreas Rolfs、Jürgen Liebscher、Birgit Müller、Hans-Jörg Hofmann

  DOI：10.1021/jm970327j

  日期：1998.1.1

  Starting from the corresponding acetophenone and glycine derivatives, a series of new 3-aminopyrroles was synthesized in few steps. Using this procedure with hydrazine and hydroxylamine instead of the glycinates provides access to S-aminopyrazoles and 5-amino-1,2-oxazoles. The various derivatives were tested for anticonvulsant activity in a variety of test models. Several compounds exhibit considerable activity with a remarkable lack of neurotoxicity. 4-(4-Bromophenyl)-3-morpholinopyrrole-2-carboxylic acid methyl ester, 3, proved to be the most active compound. It was protective in the maximal electroshock seizure (MES) test in rats with an oral ED50 of 2.5 mg/kg with no neurotoxicity noted at doses up to 500 mg/kg. Compound 3 blocks sodium channels in a frequency-dependent manner. The essential structural features which could be responsible for an interaction with an active site of the voltage-dependent sodium channel are established within a suggested pharmacophore model.