3-(5-methoxy-1-oxo-2,3-dihydro-1H-isoindol-2-yl)piperidine-2,6-dione | 1416990-14-1

• 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: 3-(5-methoxy-1-oxo-2,3-dihydro-1H-isoindol-2-yl)piperidine-2,6-dione
• 英文别名: 3-(6-methoxy-3-oxo-1H-isoindol-2-yl)piperidine-2,6-dione
• CAS: 1416990-14-1
• 化学式: C₁₄H₁₄N₂O₄
• 分子量: 274.276
• InChiKey: UCRSTLCVZRQISL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  75.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-甲氧基-2-甲基苯甲酸 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 碳酸氢钠 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 3-(5-methoxy-1-oxo-2,3-dihydro-1H-isoindol-2-yl)piperidine-2,6-dione
  参考文献：
  名称：

  来那度胺和泊马利度胺的等规类似物：合成与生物活性

  摘要：

  制备了一系列免疫调节药物来那度胺（1）和pomalidomide（2）的类似物，其中的氨基被各种等排物取代，并测定了其免疫调节活性和针对癌细胞系的活性。4-甲基和4-氯类似物4和15分别在LPS刺激的hPBMC中显示出对肿瘤坏死因子-α（TNF-α）的有效抑制作用，在人T细胞共刺激测定中对IL-2的有效刺激作用，以及对Namalwa淋巴瘤细胞系的抗增殖活性。这两种类似物在大鼠中均显示出口服生物利用度。

  DOI：

  10.1016/j.bmcl.2012.10.071

文献信息

• TAU-PROTEIN TARGETING PROTACS AND ASSOCIATED METHODS OF USE
  申请人：Arvinas, Inc.

  公开号：US20180125821A1

  公开（公告）日：2018-05-10

  The present disclosure relates to bifunctional compounds, which find utility as modulators of tau protein. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a VHL or cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds tau protein, such that tau protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of tau. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of tau protein. Diseases or disorders that result from aggregation or accumulation of tau protein are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，其作为tau蛋白的调节剂具有实用性。具体而言，本公开涉及含有一端结合到E3泛素连接酶的VHL或cereblon配体，另一端结合到tau蛋白的双功能化合物，使得tau蛋白与泛素连接酶靠近，以实现tau蛋白的降解（和抑制）。本公开展示了与tau蛋白降解/抑制相关的广泛药理活性。本公开的化合物和组合物用于治疗或预防由tau蛋白聚集或积累导致的疾病或紊乱。
• [EN] COMPOUNDS AND METHODS OF TREATING CANCERS<br/>[FR] COMPOSÉS ET MÉTHODES DE TRAITEMENT DE CANCERS
  申请人：CULLGEN SHANGHAI INC

  公开号：WO2020200291A1

  公开（公告）日：2020-10-08

  This disclosure relates to heterobifunctional compounds (e.g., bi-functional small molecule compounds), compositions comprising one or more of the heterobifunctional compounds, and to methods of use the heterobifunctional compounds for the treatment of certain disease in a subject in need thereof. The disclosure also relates to methods for identifying such heterobifunctional compounds.

  这份披露涉及异双功能化合物（例如，双功能小分子化合物），包括一种或多种异双功能化合物的组合物，以及使用这些异双功能化合物治疗患有特定疾病的需要该类治疗的受试者的方法。该披露还涉及识别此类异双功能化合物的方法。
• [EN] BIFUNCTIONAL MOLECULES CONTAINING AN E3 UBIQUITINE LIGASE BINDING MOIETY LINKED TO A BCL6 TARGETING MOIETY<br/>[FR] MOLÉCULES BIFONCTIONNELLES CONTENANT UNE FRACTION DE LIAISON À L'UBIQUITINE LIGASE E3 LIÉE À UNE FRACTION CIBLANT BCL6
  申请人：ARVINAS OPERATIONS INC

  公开号：WO2021077010A1

  公开（公告）日：2021-04-22

  Bifunctional compounds, which find utility as modulators of B-cell lymphoma 6 protein (BCL6; target protein), are described herein. In particular, the bifunctional compounds of the present disclosure contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand that binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

  本发明描述了双功能化合物，其作为B细胞淋巴瘤6蛋白（BCL6；靶蛋白）的调节剂。特别是，本发明中的双功能化合物一端含有与相应的E3泛素连接酶结合的Von Hippel-Lindau、cereblon、凋亡蛋白抑制剂或小鼠双分钟同源蛋白2的配体，另一端含有与靶蛋白结合的部分，使得靶蛋白被置于泛素连接酶附近，以促进靶蛋白的降解（和抑制）。本发明中的双功能化合物展示了与靶蛋白降解/抑制相关的广泛药理活性。可以通过本发明中的化合物和组合物治疗或预防由靶蛋白聚集或积累引起的疾病或失调。
• CEREBLON LIGANDS AND BIFUNCTIONAL COMPOUNDS COMPRISING THE SAME
  申请人：Arvinas, Inc.

  公开号：US20180215731A1

  公开（公告）日：2018-08-02

  The description relates to cereblon E3 ligase binding compounds, including bifunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present disclosure. In particular, the description provides compounds, which contain on one end a ligand which binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.

  该描述涉及cereblon E3连接酶结合化合物，包括包含相同成分的双功能化合物，这些化合物作为靶向泛素化的调节剂具有实用价值，尤其是抑制剂，可降解和/或以其他方式抑制根据本公开的双功能化合物。特别是，该描述提供了化合物，其一端含有与cereblon E3泛素连接酶结合的配体，另一端含有与目标蛋白结合的部分，使目标蛋白位于泛素连接酶附近以降解（和抑制）该蛋白。可以合成表现出广泛药理活性的化合物，与几乎所有类型的靶向多肽的降解/抑制一致。
• [EN] COMPOUNDS THAT INDUCE DEGRADATION OF ANTI-APOPTOTIC BCL-2 FAMILY PROTEINS AND THE USES THEREOF<br/>[FR] COMPOSÉS INDUISANT LA DÉGRADATION DE PROTÉINES ANTI-APOPTOTIQUES DE LA FAMILLE BCL-2 ET UTILISATION DE CES DERNIERS
  申请人：BIOVENTURES LLC

  公开号：WO2017184995A1

  公开（公告）日：2017-10-26

  The present disclosure provides compositions and methods for selectively killing senescent cells, wherein the composition comprises a compound of Formula (I) or a compound of Formula (II). The selective killing of senescent cells may delay aging and/or treat age-related disorders.

  本公开提供了一种用于选择性杀灭衰老细胞的组合物和方法，其中该组合物包括式(I)的化合物或式(II)的化合物。对衰老细胞的选择性杀灭可能延缓衰老和/或治疗与年龄相关的疾病。