5-bromo-N-1-isobutylbenzene-1,2-diamine | 939054-44-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 5-bromo-N-1-isobutylbenzene-1,2-diamine
• 英文别名: (2-amino-5-bromophenyl)(2-methylpropyl)amine；1,2-Benzenediamine, 4-bromo-N2-(2-methylpropyl)-；4-bromo-2-N-(2-methylpropyl)benzene-1,2-diamine
• CAS: 939054-44-1
• 化学式: C₁₀H₁₅BrN₂
• 分子量: 243.146
• InChiKey: YLKYKUWMVPWWCJ-UHFFFAOYSA-N

物化性质

• 沸点：
  323.8±32.0 °C(Predicted)
• 密度：
  1.371±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  38
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-bromo-N-1-isobutylbenzene-1,2-diamine 在 sodium hydride 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 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 在 铁粉 、 氯化铵 作用下， 以 乙醇 、 1,2-二氯乙烷 为溶剂， 反应 13.0h， 生成 5-bromo-N-1-isobutylbenzene-1,2-diamine
  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

文献信息

• GLUCOKINASE ACTIVATORS
  申请人：Cao X. Sheldon

  公开号：US20070197532A1

  公开（公告）日：2007-08-23

  Compounds, pharmaceutical compositions, kits and methods are provided for use with glucokinase that comprise a compound selected from the group consisting of: wherein the variables are as defined herein.

  提供了用于与葡萄糖激酶一起使用的化合物、药物组合物、试剂盒和方法，其中包括从以下组中选择的化合物：其中变量如本文所定义。
• [EN] BENZIMIDAZOLE DERIVATIVES AS ANTIVIRAL AGENTS<br/>[FR] DÉRIVÉS DE BENZIMIDAZOLE EN TANT QU'AGENTS ANTIVIRAUX
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2012174312A3

  公开（公告）日：2013-02-28
• Discovery of a series of dihydroquinoxalin-2(1H)-ones as selective BET inhibitors from a dual PLK1-BRD4 inhibitor
  作者：Jianping Hu、Yingqing Wang、Yanlian Li、Lin Xu、Danyan Cao、ShanShan Song、Mohammadali Soleimani Damaneh、Xin Wang、Tao Meng、Yue-Lei Chen、Jingkang Shen、Zehong Miao、Bing Xiong

  DOI：10.1016/j.ejmech.2017.05.049

  日期：2017.9

  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.