5-bromo-N-(2-methoxyethyl)-2-nitroaniline | 813448-99-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-bromo-N-(2-methoxyethyl)-2-nitroaniline
• CAS: 813448-99-6
• 化学式: C₉H₁₁BrN₂O₃
• 分子量: 275.102
• InChiKey: JJFMQWASZXTBCF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  67.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-bromo-N-(2-methoxyethyl)-2-nitroaniline 在 铁粉 、 sodium hydride 、 氯化铵 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成
  参考文献：
  名称：

  Discovery of a series of dihydroquinoxalin-2(1H)-ones as selective BET inhibitors from a dual PLK1-BRD4 inhibitor

  摘要：

  Recent years have seen much effort to discover new chemotypes of BRD4 inhibitors. Interestingly, some kinase inhibitors have been demonstrated to be potent bromodomain inhibitors, especially the PLK1 inhibitor BI-2536 and the JAK2 inhibitor TG101209, which can bind to BRD4 with IC50 values of 0.025 mu M and 0.13 mu M, respectively. Although the concept of dual inhibition is intriguing, selective BRD4 inhibitors are preferred as they may diminish off-target effects and provide more flexibility in anticancer drug combination therapy. Inspired by BI-2536, we designed and prepared a series of dihydroquinoxalin2(1H)-one derivatives as selective bromodomain inhibitors. We found compound 54 had slightly higher activity than (+)-JQ1 in the fluorescence anisotropy assay and potent antiproliferative cellular activity in the MM.1S cell line. We have successfully solved the cocrystal structure of 52 in complex with BRD4-BD1, providing a solid structural basis for the binding mode of compounds of this series. Compound 54 exhibited high selectivity over most non-BET subfamily members and did not show bioactivity towards the PLK1 kinase at 10 or 1 mu M. From in vivo studies, compound 54 demonstrated a good PK profile, and the results from in vivo pharmacological studies clearly showed the efficacy of 54 in the mouse MM.1S xenograft model. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.05.049
• 作为产物：
  描述：

  2-氟-4-溴硝基苯 、 2-甲氧基乙胺 在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以89%的产率得到5-bromo-N-(2-methoxyethyl)-2-nitroaniline
  参考文献：
  名称：

  [EN] SUBSTITUTED BENZIMIDAZOLES, THEIR PREPARATION AND THEIR USE AS PHARMACEUTICALS
  [FR] BENZIMIDAZOLES SUBSTITUÉS, PRÉPARATION ET UTILISATION DE CEUX-CI EN TANT QU'AGENTS PHARMACEUTIQUES

  摘要：

  本申请涉及到式(I)的取代苯并咪唑化合物，包括它们的组合物以及它们在治疗疾病和病况中的用途，其中需要抑制溴结构域。例如，本申请涉及到取代苯并咪唑化合物及其作为溴结构域抑制剂的用途。本申请还涉及到治疗或预防增生性疾病、自身免疫性疾病、炎症性疾病、皮肤疾病以及新生物，包括肿瘤和/或癌症。

  公开号：

  WO2017024412A1

文献信息

• [EN] IMIDAZOLYL-IMIDAZOLES AS KINASE INHIBITORS<br/>[FR] IMIDAZOLYL-IMIDAZOLES EN TANT QU'INHIBITEURS DE KINASE
  申请人：GLAXO GROUP LTD

  公开号：WO2011123609A1

  公开（公告）日：2011-10-06

  Disclosed are compounds having the formula: wherein R1A, R1B, R2 and R3 are as defined herein, and methods of making and using the same.

  揭示了具有以下公式的化合物：其中R1A、R1B、R2和R3如本文所定义，并且制备和使用这些化合物的方法。
• [EN] 4- (HETEROCYCLYL- FUSED PHENYL)- 3- (PHENYL OR PYRID -2- YL) PYRAZOLES AS INHIBITORS OF THE ALK-5- RECEPTOR<br/>[FR] 4-(HETEROCYCLYLE-PHENYLE FUSIONNE)-3-PHENYLE OU PYRID-2-YLE)PYRAZOLES UTILISES COMME INHIBITEURS DU RECEPTEUR DE ALK-5
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2004111036A1

  公开（公告）日：2004-12-23

  The invention relates to novel pyrazole derivatives which are inhibitors of the transforming growth factor, ('TGF')-β signalling pathway, in particular, the phosphorylation of smad2 or smad3 by the TGF-β type I or activin-like kinase ('ALK')-5 receptor, methods for their preparation and their use in medicine, specifically in the treatment and prevention of a disease state mediated by this pathway.

  这项发明涉及新型吡唑衍生物，它们是转化生长因子（'TGF'）-β信号通路的抑制剂，特别是通过TGF-β类型I或类活化素激酶（'ALK'）-5受体对smad2或smad3的磷酸化的抑制剂，以及它们的制备方法和在医学上的应用，具体用于治疗和预防由该通路介导的疾病状态。
• COMPOUNDS AND THEIR METHODS OF USE
  申请人：Praxis Precision Medicines, Inc.

  公开号：US20210355118A1

  公开（公告）日：2021-11-18

  The present invention is directed to, in part, fused heteroaryl compounds and compositions useful for preventing and/or treating a disease or condition relating to aberrant function of a voltage-gated, sodium ion channel, for example, abnormal late/persistent sodium current. Methods of treating a disease or condition relating to aberrant function of a sodium ion channel including Dravet syndrome or epilepsy are also provided herein.

  本发明部分涉及融合的杂环基化合物和组合物，用于预防和/或治疗与电压门控钠离子通道异常功能相关的疾病或症状，例如异常的晚期/持续性钠电流。本文还提供了治疗与钠离子通道异常功能相关的疾病或症状，包括德雷维特综合征或癫痫的方法。
• Thiazoles inhibitors of the alk-5 receptor
  申请人：Dodic Nerina

  公开号：US20060247233A1

  公开（公告）日：2006-11-02

  The invention relates to novel aminothiazole derivatives which are inhibitors of the transforming growth factor, (“TGF”)-β signaling pathway, in particular, the phosphorylation of smad2 or smad3 by the TGF-β type I or activin-like kinase (“ALK”)-5 receptor, methods for their preparation and their use in medicine, specifically in the treatment and prevention of a disease state mediated by this pathway

  本发明涉及新型氨基噻唑衍生物，其是转化生长因子（“TGF”）-β信号通路的抑制剂，特别是通过TGF-β类型I或类活性素激酶（“ALK”）-5受体的smad2或smad3的磷酸化，其制备方法及其在医学上的用途，特别是在治疗和预防由该通路介导的疾病状态方面的用途。
• IMIDAZOLYL-IMIDAZOLES AS KINASE INHIBITORS
  申请人：Bodmer Vera Q.

  公开号：US20130018039A1

  公开（公告）日：2013-01-17

  Disclosed are compounds having the formula: wherein R 1A , R 1B , R 2 and R 3 are defined herein, and methods of making and using the same.

  本发明涉及具有以下式的化合物：其中R1A，R1B，R2和R3如本文所定义，并且涉及其制备和使用的方法。