(S)-4,5-二氨基-5-氧代-戊酸甲酯 | 70830-50-1

• 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
• 中文名称: (S)-4,5-二氨基-5-氧代-戊酸甲酯
• 英文名称: methyl (4S)-4,5-diamino-5-oxopentanoate hydrochloride
• 英文别名: (S)-methyl 4,5-diamino-5-oxopentanoate hydrochloride；methyl (4S)-4,5-diamino-5-oxopentanoate;hydrochloride
• CAS: 70830-50-1
• 化学式: C₆H₁₂N₂O₃*ClH
• 分子量: 196.634
• InChiKey: CFJYPWQHBLMCCU-WCCKRBBISA-N

物化性质

• 沸点：
  341.3±37.0 °C(Predicted)
• 密度：
  1.178±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.83
• 重原子数：
  12
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  95.4
• 氢给体数：
  3
• 氢受体数：
  4

安全信息

• 储存条件：
  存储条件：2-8°C，避光。

反应信息

• 作为反应物：
  描述：

  (S)-4,5-二氨基-5-氧代-戊酸甲酯 在 potassium tert-butylate 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 14.5h， 生成 (S)-3-(4-((4-(吗啉基甲基)苄基)氧基)-1-氧代异吲哚啉-2-基)哌啶-2,6-二酮
  参考文献：
  名称：

  A Cereblon Modulator (CC-220) with Improved Degradation of Ikaros and Aiolos

  摘要：

  The drugs lenalidomide and pomalidomide bind to the protein cereblon, directing the CRL4-CRBN E3 ligase toward the transcription factors Ikaros and Aiolos to cause their ubiquitination and degradation. Here we describe CC-220 (compound 6), a cereblon modulator in clinical development for systemic lupus erythematosis and relapsed/refractory multiple myeloma. Compound 6 binds cereblon with a higher affinity than lenalidomide or pomalidomide. Consistent with this, the cellular degradation of Ikaros and Aiolos is more potent and the extent of substrate depletion is greater. The crystal structure of cereblon in complex with DDB1 and compound 6 reveals that the increase in potency correlates with increased contacts between compound 6 and cereblon away from the modeled binding site for Ikaros/Aiolos. These results describe a new cereblon modulator which achieves greater substrate degradation via tighter binding to the cereblon E3 ligase and provides an example of the effect of E3 ligase binding affinity with relevance to other drug discovery efforts in targeted protein degradation.

  DOI：

  10.1021/acs.jmedchem.6b01921

文献信息

• [EN] COMPOUNDS FOR THE MODULATION OF RIP2 KINASE ACTIVITY<br/>[FR] COMPOSÉS POUR LA MODULATION DE L'ACTIVITÉ DE LA KINASE RIP2
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2017046036A1

  公开（公告）日：2017-03-23

  The present invention relates to compounds, compositions, combinations and medicaments containing said compounds and processes for their preparation. The invention also relates to the use of said compounds, combinations, compositions and medicaments, for example as inhibitors of the activity of RIP2 kinase, including degrading RIP2 kinase, the treatment of diseases and conditions mediated by the RIP2 kinase, in particular for the treatment of inflammatory diseases or conditions.

  本发明涉及含有所述化合物的化合物、组合物、组合物和药物以及其制备方法。该发明还涉及所述化合物、组合物、组合物和药物的用途，例如作为RIP2激酶活性的抑制剂，包括降解RIP2激酶，用于治疗由RIP2激酶介导的疾病和症状，特别是用于治疗炎症性疾病或症状。
• Arylmethoxy Isoindoline Derivatives and Compositions Comprising and Methods of Using the Same
  申请人：Man Hon-Wah

  公开号：US20110196150A1

  公开（公告）日：2011-08-11

  Provided are 4′-arylmethoxy isoindoline compounds, and pharmaceutically acceptable salts, solvates, clathrates, stereoisomers, and prodrugs thereof. Methods of use, and pharmaceutical compositions of these compounds are disclosed.

  提供了4'-芳基甲氧基异吲哚啉化合物，以及其药用盐、溶剂合物、包合物、立体异构体和前药。公开了这些化合物的使用方法和药物组合物。
• ARYLMETHOXY ISOINDOLINE DERIVATIVES AND COMPOSITIONS COMPRISING AND METHODS OF USING THE SAME
  申请人：Celgene Corporation

  公开号：US20180037567A1

  公开（公告）日：2018-02-08

  Provided are 4′-arylmethoxy isoindoline compounds, and pharmaceutically acceptable salts, solvates, clathrates, stereoisomers, and prodrugs thereof. Methods of use, and pharmaceutical compositions of these compounds are disclosed.

  提供了4'-芳基甲氧基异吲哚啉化合物及其药学上可接受的盐、溶剂合物、笼合物、立体异构体和前药。公开了这些化合物的使用方法和药物组合物。
• ISOINDOLINE COMPOUND, AND PREPARATION METHOD, PHARMACEUTICAL COMPOSITION, AND APPLICATION OF ISOINDOLINE COMPOUND
  申请人：Shanghai Institute of Materia Medica, Chinese Academy of Sciences

  公开号：EP3896062A1

  公开（公告）日：2021-10-20

  The present invention relates to an isoindoline compound as represented by general formula (I) and used as a CRBN regulator, and a preparation method, a pharmaceutical composition, and an application of the isoindoline compound. Specifically, a class of polysubstituted isoindoline compound provided in the present invention, as a class of CRL4CRBN E3 ubiquitin ligase regulator having a novel structure, has good anti-tumor activity and immunoregulatory activity, and can be used for preparing drugs for treating diseases associated with a CRL4CRBN E3 ubiquitin ligase.

  本发明涉及一种由通式(I)表示并用作CRBN调节剂的异吲哚啉化合物，以及该异吲哚啉化合物的制备方法、药物组合物和应用。具体而言，本发明提供的一类多取代异吲哚啉化合物，作为一类结构新颖的CRL4CRBN E3泛素连接酶调节剂，具有良好的抗肿瘤活性和免疫调节活性，可用于制备治疗与CRL4CRBN E3泛素连接酶相关疾病的药物。
• Arylmethoxy isoindoline derivatives and compositions comprising and methods of using the same
  申请人：Celgene Corporation

  公开号：US10189814B2

  公开（公告）日：2019-01-29

  Provided are 4′-arylmethoxy isoindoline compounds, and pharmaceutically acceptable salts, solvates, clathrates, stereoisomers, and prodrugs thereof. Methods of use, and pharmaceutical compositions of these compounds are disclosed.

  本发明提供了 4′-芳基甲氧基异吲哚啉化合物及其药学上可接受的盐、溶液剂、凝胶体、立体异构体和原药。还公开了这些化合物的使用方法和药物组合物。