2-chloro-N-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)acetamide | 1957235-51-6

• 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: 2-chloro-N-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)acetamide
• 英文别名: 2-chloro-N-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]acetamide
• CAS: 1957235-51-6
• 化学式: C₁₅H₁₂ClN₃O₅
• 分子量: 349.73
• InChiKey: OIDIVJNMVBHPAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  113
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 危险类别：
  8
• 危险性防范说明：
  P201,P202,P261,P264,P270,P271,P280,P302+P352,P304+P340,P308+P313,P310,P330,P361,P403+P233,P405,P501
• 危险品运输编号：
  1759
• 危险性描述：
  H302,H314
• 包装等级：
  III

反应信息

• 作为反应物：
  描述：

  2-chloro-N-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)acetamide 、 N-[4-[[4-[1-(3-chloro-5-cyano-4-hydroxyphenyl)-1-methylethyl]phenoxy]methyl]pyrimidin-2-yl]-N-[(4-methoxyphenyl)methyl]methanesulfonamide 在 diisopropyl (E)-azodicarboxylate 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 以55.5 %的产率得到tert-butyl 3-[2-chloro-6-cyano-4-[1-[4-[[2-[(4-methoxyphenyl)methyl-methylsulfonyl-amino]pyrimidin-4-yl]methoxy]phenyl]-1-methylethyl]phenoxy]azetidine-1-carboxylate
  参考文献：
  名称：

  [EN] ANDROGEN RECEPTOR MODULATORS AND METHODS FOR USE AS BIFUNCTIONAL DEGRADERS
  [FR] MODULATEURS DE RÉCEPTEURS DES ANDROGÈNES ET PROCÉDÉS D'UTILISATION EN TANT QU'AGENTS DE DÉGRADATION BIFONCTIONNELS

  摘要：

  The present invention relates to bifunctional chemical protein degraders comprising a ligase modulator/binder and a molecule that binds to a protein target of interest, and methods of treating various diseases and conditions with the degrader compounds, including diseases associated with androgen receptors.

  公开号：

  WO2023056423A1
• 作为产物：
  描述：

  氯乙酰氯 、 525-氨基-2-(26-二氧代哌啶-3-基)异二氢吲哚-13-二酮 以 四氢呋喃 为溶剂， 以93.8 %的产率得到2-chloro-N-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)acetamide
  参考文献：
  名称：

  [EN] ANDROGEN RECEPTOR MODULATORS AND METHODS FOR USE AS BIFUNCTIONAL DEGRADERS
  [FR] MODULATEURS DE RÉCEPTEURS DES ANDROGÈNES ET PROCÉDÉS D'UTILISATION EN TANT QU'AGENTS DE DÉGRADATION BIFONCTIONNELS

  摘要：

  The present invention relates to bifunctional chemical protein degraders comprising a ligase modulator/binder and a molecule that binds to a protein target of interest, and methods of treating various diseases and conditions with the degrader compounds, including diseases associated with androgen receptors.

  公开号：

  WO2023056423A1

文献信息

• [EN] TUNABLE ENDOGENOUS PROTEIN DEGRADATION WITH HETEROBIFUNCTIONAL COMPOUNDS<br/>[FR] DÉGRADATION MODULABLE DE PROTÉINE ENDOGÈNE AVEC DES COMPOSÉS HÉTÉROBIFONCTIONNELS
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2018148443A1

  公开（公告）日：2018-08-16

  The present invention provides a means to modulate gene expression in vivo in a manner that avoids problems associated with CRISPR endogenous protein knock-out or knock-in strategies and strategies that provide for correction, or alteration, of single nucleotides. The invention includes inserting into the genome a nucleotide encoding a heterobifunctional compound targeting protein (dTAG) in-frame with the nucleotide sequence of a gene encoding an endogenously expressed protein of interest which, upon expression, produces an endogenous protein-dTAG hybrid protein. This allows for targeted protein degradation of the dTAG and the fused endogenous protein using a heterobifunctional compound.

  本发明提供了一种在体内调节基因表达的方法，避免了与CRISPR内源蛋白敲除或敲入策略以及提供单个核苷酸修正或改变的策略相关的问题。该发明包括将编码靶向蛋白（dTAG）的异双功能化合物的核苷酸插入基因组中，与编码感兴趣的内源表达蛋白的基因的核苷酸序列同框，表达后产生内源蛋白-dTAG杂交蛋白。这允许使用异双功能化合物对dTAG和融合的内源蛋白进行靶向蛋白降解。
• Methods to induce targeted protein degradation through bifunctional molecules
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：US10125114B2

  公开（公告）日：2018-11-13

  The present application provides bifunctional compounds which act as protein degradation inducing moieties. The present application also relates to methods for the targeted degradation of endogenous proteins through the use of the bifunctional compounds that link a cereblon-binding moiety to a ligand that is capable of binding to the targeted protein which can be utilized in the treatment of proliferative disorders. The present application also provides methods for making compounds of the application and intermediates thereof.

  本申请提供了作为蛋白质降解诱导分子的双功能化合物。本申请还涉及通过使用双官能化合物靶向降解内源性蛋白质的方法，该双官能化合物将脑龙结合分子与能够与靶向蛋白质结合的配体连接起来，可用于治疗增殖性疾病。本申请还提供了制造本申请化合物及其中间体的方法。
• Targeted protein degradation to attenuate adoptive T-cell therapy associated adverse inflammatory responses
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：US11046954B2

  公开（公告）日：2021-06-29

  This invention is in the area of compositions and methods for regulating chimeric antigen receptor immune effector cell, for example T-cell (CAR-T), therapy to modulate associated adverse inflammatory responses, for example, cytokine release syndrome and tumor lysis syndrome, using targeted protein degradation.

  本发明属于利用靶向蛋白降解调节嵌合抗原受体免疫效应细胞（例如 T 细胞（CAR-T））疗法以调节相关不良炎症反应（例如细胞因子释放综合征和肿瘤溶解综合征）的组合物和方法领域。
• Regulating chimeric antigen receptors
  申请人：DANA-FARBER CANCER INSTITUTE, INC.

  公开号：US11311609B2

  公开（公告）日：2022-04-26

  This invention is in the area of compositions and methods for regulating chimeric antigen receptor immune effector cell, for example T-cell (CAR-T), therapy to modulate associated adverse inflammatory responses, for example, cytokine release syndrome and tumor lysis syndrome, using targeted protein degradation.

  本发明属于利用靶向蛋白降解调节嵌合抗原受体免疫效应细胞（例如 T 细胞（CAR-T））疗法以调节相关不良炎症反应（例如细胞因子释放综合征和肿瘤溶解综合征）的组合物和方法领域。
• TARGETED PROTEIN DEGRADATION TO ATTENUATE ADOPTIVE T-CELL THERAPY ASSOCIATED ADVERSE INFLAMMATORY RESPONSES
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：EP3331905A1

  公开（公告）日：2018-06-13