4-bromo-N-(2,6-dioxopiperidin-3-yl)benzamide

• 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: 4-bromo-N-(2,6-dioxopiperidin-3-yl)benzamide
• 化学式: C₁₂H₁₁BrN₂O₃
• mdl: MFCD22748654
• 分子量: 311.135
• InChiKey: LPCQTAJHFUWPDE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  75.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-溴苯甲酸 、 3-氨基-2,6-哌啶二酮盐酸盐 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以85%的产率得到4-bromo-N-(2,6-dioxopiperidin-3-yl)benzamide
  参考文献：
  名称：

  A Cell-Based Target Engagement Assay for the Identification of Cereblon E3 Ubiquitin Ligase Ligands and Their Application in HDAC6 Degraders

  摘要：

  Proteolysis-targeting chimeras (PROTACs) is a paradigm shift for small-molecule drug discovery. However, limited E3 ubiquitin ligase ligands with cellular activity are available. In vitro binding assays involve the expression and purification of a large amount of proteins and they often yield ligands that are inactive in cell-based assays due to poor cell permeability, stability, and other reasons. Herein, we report the development of a practical and efficient cell-based target engagement assay to evaluate the binding affinity of a small library of cereblon ligands to its E3 ligase in cells. Selected cell-permeable E3 ligase ligands derived from this assay are then used to construct HDAC6 degraders with cellular protein degradation activity. Because the assay does not involve any genetic engineering, it is relatively easy to transfer from one cell type to a different one.

  DOI：

  10.1016/j.chembiol.2020.04.008

文献信息

• [EN] AMINE-LINKED C3-GLUTARIMIDE DEGRONIMERS FOR TARGET PROTEIN DEGRADATION<br/>[FR] DÉGRONIMÈRES DE C3-GLUTARIMIDE LIÉS À UNE AMINE POUR LA DÉGRADATION DE PROTÉINES CIBLES
  申请人：C4 THERAPEUTICS INC

  公开号：WO2017197051A1

  公开（公告）日：2017-11-16

  This invention provides amine-linked C3-glutarimide Degronimers and Degrons for therapeutic applications as described further herein, and methods of use and compositions thereof as well as methods for their preparation.

  这项发明提供了胺连接的C3-戊二酰亚胺Degronimers和Degrons，用于治疗应用，如本文进一步描述的，以及它们的使用方法、组合物以及它们的制备方法。
• AMINE-LINKED C3-GLUTARIMIDE DEGRONIMERS FOR TARGET PROTEIN DEGRADATION
  申请人：C4 Therapeutics, Inc.

  公开号：EP3455219A1

  公开（公告）日：2019-03-20
• A Cell-Based Target Engagement Assay for the Identification of Cereblon E3 Ubiquitin Ligase Ligands and Their Application in HDAC6 Degraders
  作者：Ka Yang、Yu Zhao、Xueqing Nie、Hao Wu、Bo Wang、Chelsi M. Almodovar-Rivera、Haibo Xie、Weiping Tang

  DOI：10.1016/j.chembiol.2020.04.008

  日期：2020.7

  Proteolysis-targeting chimeras (PROTACs) is a paradigm shift for small-molecule drug discovery. However, limited E3 ubiquitin ligase ligands with cellular activity are available. In vitro binding assays involve the expression and purification of a large amount of proteins and they often yield ligands that are inactive in cell-based assays due to poor cell permeability, stability, and other reasons. Herein, we report the development of a practical and efficient cell-based target engagement assay to evaluate the binding affinity of a small library of cereblon ligands to its E3 ligase in cells. Selected cell-permeable E3 ligase ligands derived from this assay are then used to construct HDAC6 degraders with cellular protein degradation activity. Because the assay does not involve any genetic engineering, it is relatively easy to transfer from one cell type to a different one.