N-methylisoindoline-5-carboxamide | 137453-27-1

• 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: N-methylisoindoline-5-carboxamide
• 英文别名: N-methyl-2,3-dihydro-1H-isoindole-5-carboxamide
• CAS: 137453-27-1
• 化学式: C₁₀H₁₂N₂O
• 分子量: 176.218
• InChiKey: KQXJFSLXGQBRFO-UHFFFAOYSA-N

物化性质

• 沸点：
  316.6±42.0 °C(Predicted)
• 密度：
  1.137±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  41.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  BOC-D-2,4-二氯苯丙氨酸 、 N-methylisoindoline-5-carboxamide 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以36%的产率得到
  参考文献：
  名称：

  Potent non-hydroxamate inhibitors of histone deacetylase-8: Role and scope of an isoindolin-2-yl linker with an α-amino amide as the zinc-binding unit

  摘要：

  A series of potent inhibitors of histone deacetylase-8 (HDAC8) is described that contains an a-amino amide zincbinding unit and a substituted isoindolinyl capping group. The presence of a 2,4-dichlorophenyl unit located in the acetate-release cavity was shown to confer a gain of approx. 4.3 kJ mol(-1) in binding energy compared to a phenyl group, and the isoindoline linker has approx. 5.8 kJ mol(-1) greater binding energy than the corresponding tetrahydroisoquinoline ring system. In a series of 5-substituted isoindolin-2-yl inhibitors, a 5-acetylamino derivative was found to be more potent than the 5-unsubstituted lead HDAC8 inhibitor (increase in binding energy of 2.0 kJ mol(-1), ascribed to additional binding interactions within the N-epsilon-acetyl-L-lysine binding tunnel in HDAC8, including hydrogen bonding to Asp101. Tolerance of a 5-substituent (capping group) on the isoindoline ring has been demonstrated, and which in some cases confers improved enzyme inhibition, the HDAC8 substrate-binding region providing a platform for additional interactions.

  DOI：

  10.1016/j.bmcl.2019.126926
• 作为产物：
  描述：

  2-benzylisoindoline-5-carboxylic acid 在 palladium on activated charcoal 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0~30.0 ℃ 、101.33 kPa 条件下， 反应 88.5h， 生成 N-methylisoindoline-5-carboxamide
  参考文献：
  名称：

  Potent non-hydroxamate inhibitors of histone deacetylase-8: Role and scope of an isoindolin-2-yl linker with an α-amino amide as the zinc-binding unit

  摘要：

  A series of potent inhibitors of histone deacetylase-8 (HDAC8) is described that contains an a-amino amide zincbinding unit and a substituted isoindolinyl capping group. The presence of a 2,4-dichlorophenyl unit located in the acetate-release cavity was shown to confer a gain of approx. 4.3 kJ mol(-1) in binding energy compared to a phenyl group, and the isoindoline linker has approx. 5.8 kJ mol(-1) greater binding energy than the corresponding tetrahydroisoquinoline ring system. In a series of 5-substituted isoindolin-2-yl inhibitors, a 5-acetylamino derivative was found to be more potent than the 5-unsubstituted lead HDAC8 inhibitor (increase in binding energy of 2.0 kJ mol(-1), ascribed to additional binding interactions within the N-epsilon-acetyl-L-lysine binding tunnel in HDAC8, including hydrogen bonding to Asp101. Tolerance of a 5-substituent (capping group) on the isoindoline ring has been demonstrated, and which in some cases confers improved enzyme inhibition, the HDAC8 substrate-binding region providing a platform for additional interactions.

  DOI：

  10.1016/j.bmcl.2019.126926

文献信息

• Potent non-hydroxamate inhibitors of histone deacetylase-8: Role and scope of an isoindolin-2-yl linker with an α-amino amide as the zinc-binding unit
  作者：Simon O.R. Greenwood、A.W. Edith Chan、D. Flemming Hansen、Charles M. Marson

  DOI：10.1016/j.bmcl.2019.126926

  日期：2020.3

  A series of potent inhibitors of histone deacetylase-8 (HDAC8) is described that contains an a-amino amide zincbinding unit and a substituted isoindolinyl capping group. The presence of a 2,4-dichlorophenyl unit located in the acetate-release cavity was shown to confer a gain of approx. 4.3 kJ mol(-1) in binding energy compared to a phenyl group, and the isoindoline linker has approx. 5.8 kJ mol(-1) greater binding energy than the corresponding tetrahydroisoquinoline ring system. In a series of 5-substituted isoindolin-2-yl inhibitors, a 5-acetylamino derivative was found to be more potent than the 5-unsubstituted lead HDAC8 inhibitor (increase in binding energy of 2.0 kJ mol(-1), ascribed to additional binding interactions within the N-epsilon-acetyl-L-lysine binding tunnel in HDAC8, including hydrogen bonding to Asp101. Tolerance of a 5-substituent (capping group) on the isoindoline ring has been demonstrated, and which in some cases confers improved enzyme inhibition, the HDAC8 substrate-binding region providing a platform for additional interactions.