Methyl 3-amino-4-cyano-5-(3-methylphenoxy)thiophene-2-carboxylate | 230310-93-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Methyl 3-amino-4-cyano-5-(3-methylphenoxy)thiophene-2-carboxylate
• CAS: 230310-93-7
• 化学式: C₁₄H₁₂N₂O₃S
• 分子量: 288.327
• InChiKey: MFAHLQOCWOHUSB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  114
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Methyl 3-amino-4-cyano-5-(3-methylphenoxy)thiophene-2-carboxylate 在 硫酸 作用下， 生成 Methyl 3-amino-4-carbamoyl-5-(3-methylphenoxy)thiophene-2-carboxylate
  参考文献：
  名称：

  3-Amino-5-phenoxythiophenes:  Syntheses and Structure−Function Studies of a Novel Class of Inhibitors of Cellular l-Triiodothyronine Uptake

  摘要：

  A series of substituted 3-amino-5-phenoxythiophenes was synthesized starting from malodinitrile and carbon disulfide. The resulting dicyanoketenedithiolate reacts via Thorpe-Dieckmann cyclization with halogen methanes bearing electron-withdrawing groups to give thiophene-2-thiolates, which can be transformed into 3-amino-5-(methylsulfonyl)thiophene-4-carbonitriles. Replacement of the methylsulfonyl groups by substituted phenolates provides the substituted 3-amino-5-phenoxythiophenes. Some of the derivatives show a considerable inhibitory potency for the L-T-3 uptake in inhibition studies on human HepG2 hepatoma cells with maximum values of about 60% at a dose of 10(-5) M for the most potent 2-benzoyl derivatives. The structure of the phenoxythiophenes fits well into a general concept derived for other classes of L-T-3 uptake inhibitors, which postulates an angular and perpendicular orientation of the ring systems in these compounds as a prerequisite for an inhibitory potency. Docking studies for the phenoxythiophenes with transthyretin as a receptor model show their preferred attack at the L-T-4/L-T-3 binding channel.

  DOI：

  10.1021/jm980288r
• 作为产物：
  描述：

  3-氨基-4-氰基-5-甲硫基噻吩-2-甲酸甲酯 在 双氧水 、 sodium methylate 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 336.17h， 生成 Methyl 3-amino-4-cyano-5-(3-methylphenoxy)thiophene-2-carboxylate
  参考文献：
  名称：

  3-Amino-5-phenoxythiophenes:  Syntheses and Structure−Function Studies of a Novel Class of Inhibitors of Cellular l-Triiodothyronine Uptake

  摘要：

  A series of substituted 3-amino-5-phenoxythiophenes was synthesized starting from malodinitrile and carbon disulfide. The resulting dicyanoketenedithiolate reacts via Thorpe-Dieckmann cyclization with halogen methanes bearing electron-withdrawing groups to give thiophene-2-thiolates, which can be transformed into 3-amino-5-(methylsulfonyl)thiophene-4-carbonitriles. Replacement of the methylsulfonyl groups by substituted phenolates provides the substituted 3-amino-5-phenoxythiophenes. Some of the derivatives show a considerable inhibitory potency for the L-T-3 uptake in inhibition studies on human HepG2 hepatoma cells with maximum values of about 60% at a dose of 10(-5) M for the most potent 2-benzoyl derivatives. The structure of the phenoxythiophenes fits well into a general concept derived for other classes of L-T-3 uptake inhibitors, which postulates an angular and perpendicular orientation of the ring systems in these compounds as a prerequisite for an inhibitory potency. Docking studies for the phenoxythiophenes with transthyretin as a receptor model show their preferred attack at the L-T-4/L-T-3 binding channel.

  DOI：

  10.1021/jm980288r

文献信息

• 3-Amino-5-phenoxythiophenes:  Syntheses and Structure−Function Studies of a Novel Class of Inhibitors of Cellular <scp>l</scp>-Triiodothyronine Uptake
  作者：Detlef Briel、Dirk Pohlers、Mathias Uhlig、Silke Vieweg、Gerhard H. Scholz、Michael Thormann、Hans-Jörg Hofmann

  DOI：10.1021/jm980288r

  日期：1999.5.1

  A series of substituted 3-amino-5-phenoxythiophenes was synthesized starting from malodinitrile and carbon disulfide. The resulting dicyanoketenedithiolate reacts via Thorpe-Dieckmann cyclization with halogen methanes bearing electron-withdrawing groups to give thiophene-2-thiolates, which can be transformed into 3-amino-5-(methylsulfonyl)thiophene-4-carbonitriles. Replacement of the methylsulfonyl groups by substituted phenolates provides the substituted 3-amino-5-phenoxythiophenes. Some of the derivatives show a considerable inhibitory potency for the L-T-3 uptake in inhibition studies on human HepG2 hepatoma cells with maximum values of about 60% at a dose of 10(-5) M for the most potent 2-benzoyl derivatives. The structure of the phenoxythiophenes fits well into a general concept derived for other classes of L-T-3 uptake inhibitors, which postulates an angular and perpendicular orientation of the ring systems in these compounds as a prerequisite for an inhibitory potency. Docking studies for the phenoxythiophenes with transthyretin as a receptor model show their preferred attack at the L-T-4/L-T-3 binding channel.