(R)-tert-butyl (1-(5-aminoisoindolin-2-yl)-3-(2,4-dichlorophenyl)-1-oxopropan-2-yl)carbamate | 932720-97-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R)-tert-butyl (1-(5-aminoisoindolin-2-yl)-3-(2,4-dichlorophenyl)-1-oxopropan-2-yl)carbamate
• 英文别名: (R)-tert-butyl 1-(5-aminoisoindolin-2-yl)-3-(2,4-dichlorophenyl)-1-oxopropan-2-ylcarbamate；tert-butyl N-[(2R)-1-(5-amino-1,3-dihydroisoindol-2-yl)-3-(2,4-dichlorophenyl)-1-oxopropan-2-yl]carbamate
• CAS: 932720-97-3
• 化学式: C₂₂H₂₅Cl₂N₃O₃
• 分子量: 450.365
• InChiKey: ZUULFEONPFACTP-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  84.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-tert-butyl (1-(5-aminoisoindolin-2-yl)-3-(2,4-dichlorophenyl)-1-oxopropan-2-yl)carbamate 在 盐酸 作用下， 以 乙醚 为溶剂， 反应 0.5h， 以22%的产率得到(R)-2-amino-1-(5-aminoisoindolin-2-yl)-3-(2,4-dichlorophenyl)propan-1-one dihydrochloride
  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-苄基-5-硝基异吲哚啉 在 palladium 10% on activated carbon 、 palladium on activated charcoal 、 10 wt% Pd(OH)2 on carbon 、 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 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 (R)-tert-butyl (1-(5-aminoisoindolin-2-yl)-3-(2,4-dichlorophenyl)-1-oxopropan-2-yl)carbamate
  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
• 作为试剂：
  描述：

  (R)-tert-butyl 3-(2,4-dichlorophenyl)-1-(5-nitroisoindolin-2-yl)-1-oxopropan-2yl-carbamate 、 氢气 在 钯 sodium hydroxide 、 乙酸乙酯 、 Brine 、 Sodium sulfate-III 、 crude compound 、 (R)-tert-butyl (1-(5-aminoisoindolin-2-yl)-3-(2,4-dichlorophenyl)-1-oxopropan-2-yl)carbamate 作用下， 以 溶剂黄146 为溶剂， 反应 2.0h， 以resulting in (R)-tert-butyl 1-(5-aminoisoindolin-2-yl)-3-(2,4-dichlorophenyl)-1-oxopropan-2-ylcarbamate (92%)的产率得到(R)-tert-butyl (1-(5-aminoisoindolin-2-yl)-3-(2,4-dichlorophenyl)-1-oxopropan-2-yl)carbamate
  参考文献：
  名称：

  Carboxyamine Compounds and Methods of Use Thereof

  摘要：

  本发明涉及使用羧酰胺化合物及其盐来治疗依赖HDAC的疾病，并用于制造治疗该类疾病的药物制剂。

  公开号：

  US20080255149A1

文献信息

• WO2007/38459
  申请人：——

  公开号：——

  公开（公告）日：——
• CARBOXYAMINE COMPOUNDS AND THEIR USE IN THE TREATMENT OF HDAC DEPENDENT DISEASES
  申请人：NOVARTIS AG

  公开号：EP1996550A2

  公开（公告）日：2008-12-03
• [EN] CARBOXYAMINE COMPOUNDS AND METHODS OF USE THEREOF<br/>[FR] COMPOSES DE CARBOXYAMINE ET LEURS METHODES D'UTILISATION
  申请人：NOVARTIS AG

  公开号：WO2007038459A2

  公开（公告）日：2007-04-05

  [EN] The invention relates to the use of carboxyamine compounds and salts thereof in the treatment of HDAC dependent diseases and for the manufacture of pharmaceutical preparations for the treatment of said diseases.
  [FR] L'invention porte sur des composés de carboxyamine et leurs sels s'utilisant pour le traitement de maladies dépendant du HDAC, et pour la fabrication de préparations pharmaceutiques utilisées pour traiter lesdites maladies.