2-(2,2-dimethylpropanoyl)-N-hydroxy-1,2,3,4-tetrahydroisoquinoline-6-carboxamide | 1259296-47-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 2-(2,2-dimethylpropanoyl)-N-hydroxy-1,2,3,4-tetrahydroisoquinoline-6-carboxamide
• 英文别名: 2-(2,2-dimethylpropanoyl)-N-hydroxy-3,4-dihydro-1H-isoquinoline-6-carboxamide
• CAS: 1259296-47-3
• 化学式: C₁₅H₂₀N₂O₃
• 分子量: 276.335
• InChiKey: MDVLHAUUYXEDGR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  69.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  在 盐酸羟胺 、 potassium hydroxide 作用下， 以 甲醇 、 1,2-二氯乙烷 为溶剂， 反应 4.0h， 以8 mg的产率得到2-(2,2-dimethylpropanoyl)-N-hydroxy-1,2,3,4-tetrahydroisoquinoline-6-carboxamide
  参考文献：
  名称：

  Potent Histone Deacetylase Inhibitors Derived from 4-(Aminomethyl)-N-hydroxybenzamide with High Selectivity for the HDAC6 Isoform

  摘要：

  A screen for HDAC6 inhibitors identified acyl derivatives of 4-(aminomethyl)-N-hydroxybenzamide as potent leads with unexpected selectivity over the other subtypes. We designed and synthesized constrained heterocyclic analogues such as tetrahydroisoquinolines that show further enhanced HDAC6 selectivity and inhibitory activity in cellular assays. Selectivity may be attributed to the benzylic spacer more effectively accessing the wider channel of HDAC6 compared to other HDAC subtypes as well as hydrophobic capping groups interacting with the protein surface near the rim of the active site.

  DOI：

  10.1021/jm400385r

文献信息

• SUBSTITUTED HYDROXAMIC ACIDS AND USES THEREOF
  申请人：Millennium Pharmaceuticals, Inc.

  公开号：US20160031820A1

  公开（公告）日：2016-02-04

  This invention provides compounds of formula (I): wherein R 1 , R 2 , G, m, n, p and q have values as described in the specification, useful as inhibitors of HDAC6. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of proliferative, inflammatory, infectious, neurological or cardiovascular diseases or disorders.

  本发明提供了式（I）的化合物：其中R1，R2，G，m，n，p和q的值如说明书所述，可用作HDAC6的抑制剂。本发明还提供了包括该发明化合物的药物组合物以及使用该组合物治疗增生性、炎症性、感染性、神经系统或心血管疾病或障碍的方法。
• Substituted hydroxamic acids and uses thereof
  申请人：Blackburn Christopher

  公开号：US20110039827A1

  公开（公告）日：2011-02-17

  This invention provides compounds of formula (I): wherein R 1 , R 2 , G, m, n, p and q have values as described in the specification, useful as inhibitors of HDAC6. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of proliferative, inflammatory, infectious, neurological or cardiovascular diseases or disorders.

  本发明提供了式(I)的化合物：其中R1、R2、G、m、n、p和q的值如规范中所述，可用作HDAC6抑制剂。本发明还提供了包含本发明化合物的药物组合物以及使用这些组合物治疗增生性、炎症性、感染性、神经系统或心血管疾病或障碍的方法。
• US9096518B2
  申请人：——

  公开号：US9096518B2

  公开（公告）日：2015-08-04
• US9321731B2
  申请人：——

  公开号：US9321731B2

  公开（公告）日：2016-04-26