2-(2,6-二氧代哌啶烯-3-基)-苄甲内酰胺 | 26581-81-7

• 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
• 中文名称: 2-(2,6-二氧代哌啶烯-3-基)-苄甲内酰胺
• 英文名称: 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione
• 英文别名: EM-12；3-(1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione；3-(1,3-Dihydro-1-oxo-2h-isoindol-2-yl)-2,6-piperidinedione；3-(3-oxo-1H-isoindol-2-yl)piperidine-2,6-dione
• CAS: 26581-81-7
• 化学式: C₁₃H₁₂N₂O₃
• 分子量: 244.25
• InChiKey: WENKGSGGXGQHSH-UHFFFAOYSA-N

物化性质

• 沸点：
  383.99°C (rough estimate)
• 密度：
  1.2650 (rough estimate)
• 溶解度：
  DMF：5 mg/mL，DMF:PBS (pH 7.2) (1:4)：0.2 mg/mL，DMSO：1 mg/mL
• 物理描述：
  Em-12 is a white crystalline powder. (NTP, 1992)
• 熔点：
  460 to 464 °F (NTP, 1992)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  66.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(2,6-二氧代哌啶烯-3-基)-苄甲内酰胺 在 硫酸 、 硝酸 作用下， 生成 3-(6-nitro-1-oxoisoindolin-2-yl)piperidine-2,6-dione
  参考文献：
  名称：

  [EN] THALIDOMIDE ANALOGS AND METHODS OF USE
  [FR] ANALOGUES DE LA THALIDOMIDE ET LEURS PROCÉDÉS D'UTILISATION

  摘要：

  揭示了沙利度胺类似物及其使用方法。所述化合物的某些实施例具有抗血管生成和/或抗炎活性。所述化合物的某些实施例是非致畸的。

  公开号：

  WO2017059062A1
• 作为产物：
  描述：

  1-benzyloxy-3-(1-oxo-1,3-dihydroisoindol-2-yl)piperidine-2,6-dione 在 palladium on activated charcoal 4-二甲氨基吡啶 、 氢气 、 三乙胺 、 2-溴苯乙酮 作用下， 以 甲醇 、 乙腈 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 28.0h， 生成 2-(2,6-二氧代哌啶烯-3-基)-苄甲内酰胺
  参考文献：
  名称：

  Thalidomide Metabolites and Analogues. 3. Synthesis and Antiangiogenic Activity of the Teratogenic and TNFα-Modulatory Thalidomide Analogue 2-(2,6-Dioxopiperidine-3-yl)phthalimidine

  摘要：

  Versatile synthesis of the teratogenic, TNFalpha-modulatory, and antiangiogenic thalidomide analogue 2-(2,6-dioxopiperidine-3-yl)phthalimidine (1) and its direct antiangiogenic properties are described. With thalidomide or thalidomide derivatives as precursors, the synthesis involved either carbonyl reduction/thiation-desulfurization or carbonyl reduction/acyliminium ion reduction protocols. Compared to earlier studies with thalidomide, which was only active with microsomal treatment, I exhibited marginal inhibitory activity in the rat aortic ring assay, thereby demonstrating the requirement for metabolic activation.

  DOI：

  10.1021/jm020079d
• 作为试剂：
  描述：

  11H-苯并[C]咔唑 、 2,3,5,6-tetrafluoro-4-(4'-cyanophenyl)benzonitrile 、 sodium;hydride 、 Dichloromethane brine 在 Sodium sulfate-III 、 methanol-dichloromethane 、 2-(2,6-二氧代哌啶烯-3-基)-苄甲内酰胺 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 生成 7H-苯并[c]咔唑
  参考文献：
  名称：

  EMISSIVE COMPOUNDS FOR LIGHT EMITTING DEVICES

  摘要：

  本文揭示了由式（1）表示的化合物，其中R2是氰基、芳基和/或杂芳基，可以来自于可选取代的苯基、可选取代的吡啶基和可选取代的嘧啶基；而且，R3是杂芳基，可以来自于可选取代的咔唑基、可选取代的苯并咔唑基、可选取代的苯并噁唑基、可选取代的苯并噻唑基和可选取代的苯并吩嗪基。其他实施例提供了一种由式（1）的化合物构成的有机发光二极管器件。

  公开号：

  US20160126478A1

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。
• COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASE 4 POLYPEPTIDES
  申请人：Arvinas, Inc.

  公开号：US20190151295A1

  公开（公告）日：2019-05-23

  The present disclosure relates to bifunctional compounds, which find utility as modulators of Interleukin-1 Receptor-Associated Kinase 4 (IRAK-4); the target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hppel-Lindau, cereblon, ligand which binds to the 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 present disclosure exhibits 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.

  本公开涉及双功能化合物，其作为白细胞介素-1受体相关激酶4（IRAK-4；目标蛋白）的调节剂具有实用性。具体而言，本公开涉及包含一端结合E3泛素连接酶的Von Hppel-Lindau、cereblon配体的双功能化合物，另一端结合目标蛋白的部分，使得目标蛋白靠近泛素连接酶以实现目标蛋白的降解（和抑制）。本公开展示了与目标蛋白的降解/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目标蛋白聚集或积累导致的疾病或紊乱。
• [EN] COMPOUNDS MODULATING PROTEIN RECRUITMENT AND/OR DEGRADATION<br/>[FR] COMPOSÉS MODULANT LE RECRUTEMENT ET/OU LA DÉGRADATION DE PROTÉINES
  申请人：ORIONIS BIOSCIENCES INC

  公开号：WO2021126973A1

  公开（公告）日：2021-06-24

  The invention provides cereblon binders for the degradation of proteins by the ubiquitin proteasome pathway for therapeutic applications.

  这项发明提供了用于通过泛素蛋白酶体途径降解蛋白质的 cereblon 结合物，用于治疗应用。
• COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF ANDROGEN RECEPTOR
  申请人：Arvinas, Inc.

  公开号：US20180099940A1

  公开（公告）日：2018-04-12

  The present disclosure relates to bifunctional compounds, which find utility to degrade and (inhibit) Androgen Receptor. In particular, the present disclosure is directed to compounds, which contain on one end a cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds Androgen Receptor, such that Androgen Receptor is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of Androgen Receptor. The present disclosure exhibits a broad range of pharmacological activities associated with compounds according to the present disclosure, consistent with the degradation/inhibition of Androgen Receptor.

  本公开涉及双功能化合物，其用于降解和（抑制）雄激素受体。具体而言，本公开涉及包含一端结合到E3泛素连接酶的谷氨酰腺苷环配体，另一端结合到雄激素受体的部分的化合物，使得雄激素受体与泛素连接酶靠近，以实现雄激素受体的降解（和抑制）。本公开展示了与根据本公开涉及的化合物相关的广泛的药理活性范围，与雄激素受体的降解/抑制一致。
• Processes for the preparation of 4-amino-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione compounds
  申请人：Ge Chuanshen

  公开号：US20070004920A1

  公开（公告）日：2007-01-04

  The present invention provides new processes for the preparation of unsubstituted and substituted 4-amino-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione compounds which are usefuil, for example, for preventing or treating diseases or conditions related to an abnormally high level or activity of TNF-α. The invention can provide improved and/or efficient processes for the commercial production of unsubstituted and substituted 4-amino-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione compounds, including, but not limited to, unsubstituted 4-amino-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione.

  本发明提供了新的制备未取代和取代的4-氨基-2-(2,6-二氧杂哌啶-3-基)异吲哚啉-1,3-二酮化合物的方法，这些化合物例如可用于预防或治疗与TNF-α水平或活性异常升高相关的疾病或状况。本发明能够提供改进和/或有效的商业生产未取代和取代的4-氨基-2-(2,6-二氧杂哌啶-3-基)异吲哚啉-1,3-二酮化合物的方法，包括但不限于未取代的4-氨基-2-(2,6-二氧杂哌啶-3-基)异吲哚啉-1,3-二酮。