5-bromo-2-(2-morpholinoethoxy)benzenamine | 946786-56-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-bromo-2-(2-morpholinoethoxy)benzenamine
• 英文别名: 5-bromo-2-(2-morpholinoethoxy)aniline；5-Bromo-2-[2-(4-morpholinyl)ethoxy]aniline；5-bromo-2-(2-morpholin-4-ylethoxy)aniline
• CAS: 946786-56-7
• 化学式: C₁₂H₁₇BrN₂O₂
• mdl: MFCD08687034
• 分子量: 301.183
• InChiKey: MPMUGFHBJYPPAU-UHFFFAOYSA-N

物化性质

• 熔点：
  66-67 °C
• 沸点：
  425.3±45.0 °C(Predicted)
• 密度：
  1.414±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  47.7
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  5-bromo-2-(2-morpholinoethoxy)benzenamine 、 3-苯丙酰氯 以 二氯甲烷 为溶剂， 反应 1.0h， 以68%的产率得到N-[5-bromo-2-(2-morpholinoethoxy)phenyl]-3-phenylpropanamide
  参考文献：
  名称：

  Identification of pharmacophore model, synthesis and biological evaluation of N-phenyl-1-arylamide and N-phenylbenzenesulfonamide derivatives as BACE 1 inhibitors

  摘要：

  The pharmacophore model of arylpiperazine amide derivatives was built using Discovery Studio 2.0 software package and the best pharmacophore model ( Hypo 1) was validated by Enrichment and ROC method ( EF at 2%, 5% and 10% are 30.6, 12.2 and 7.7; AUC of the ROC curve is 0.93). According to the best pharmacophore model, 11 N-phenyl-1-arylamide, N-phenylbenzenesulfonamide derivatives, compounds 26-28, and 33a-g, were designed to be synthesized and their BACE 1 inhibitory activities were determined experimentally. Their theoretical results were in good agreement with the experimental values. Compound 33d, which displayed the highest BACE 1 activity (18.33 +/- 2.80 mu mol/L) among these two series, was chosen to study the protein binding pattern and the result showed that it was in close contact with two essential catalytic aspartates (Asp32 and Asp228) of the BACE 1. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.10.059
• 作为产物：
  描述：

  4-[2-(4-bromo-2-nitrophenoxy)ethyl]morpholine 在 tin(II) chloride dihdyrate 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 生成 5-bromo-2-(2-morpholinoethoxy)benzenamine
  参考文献：
  名称：

  双靶标的1,3-二苯脲衍生物：BACE 1抑制剂和抗阿尔茨海默氏病的金属螯合剂

  摘要：

  通过将BACE 1抑制剂1与金属螯合剂LR-90杂交，设计了双靶标的1,3-二苯脲衍生物。建立了由1,3-二苯脲衍生物组成的数据库，并通过BACE 1抑制剂的药效团模型（Hypo 1）进行了筛选。根据预测结果，选择，合成了11种Fitfit值合适的化合物（6a - d，9a - g），并对其BACE 1抑制活性进行了评估，表明预测结果与实验值非常吻合。此外，合成的化合物还显示出螯合金属离子的能力。最有效的BACE 1抑制剂9f选择（27.85±2.46μmol/ L）进行进一步的受体结合研究，结果表明在9f的脲基团和催化天冬氨酸Asp228之间形成了必不可少的氢键。

  DOI：

  10.1016/j.bmc.2010.06.042

文献信息

• Structure-based de novo design and identification of D816V mutant-selective c-KIT inhibitors
  作者：Hwangseo Park、Soyoung Lee、Suhyun Lee、Sungwoo Hong

  DOI：10.1039/c4ob00053f

  日期：——

  New 7-azaindole-based c-KIT inhibitors with nanomolar inhibitory activity and high selectivity for the gain-of-function D816V mutant were identified through the structure-based de novo design using the scoring function improved by implementing an accurate solvation free energy.

  通过使用改进的精确溶剂自由能的评分函数进行基于结构的全新设计，确定了具有纳摩尔抑制活性和对功能获得性D816V突变体高选择性的新型7-氮杂吲哚基c-KIT抑制剂。

• [EN] HETEROCYCLIC COMPOUNDS USEFUL AS MK2 INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES UTILES COMME INHIBITEURS DE MK2
  申请人：NOVARTIS AG

  公开号：WO2009010488A1

  公开（公告）日：2009-01-22

  The present invention describes tetracyclic compounds of formula (IA) or (IB), wherein the symbols R, X, A, Y, R2, R3 and D are as defined in the specification, their use in the treatment of certain diseases, e.g. depending on MK-2 or TNF activity, and ways of manufacturing them.

  本发明描述了式（IA）或（IB）的四环化合物，其中符号R、X、A、Y、R2、R3和D如规范中所定义，它们在治疗某些疾病中的用途，例如取决于MK-2或TNF活性，并制造它们的方法。
• Development and Biological Evaluation of Potent and Selective c-KIT^D816V Inhibitors
  作者：Soyoung Lee、Hyunseung Lee、Jinhee Kim、Suhyun Lee、Soo Jung Kim、Byong-Seok Choi、Soon-Sun Hong、Sungwoo Hong

  DOI：10.1021/jm500413g

  日期：2014.8.14

  The c-KIT tyrosine kinase has emerged as a potential therapeutic target for an array of diseases. However, there exists a drug resistance that is caused by mutations in c-KIT; therefore, c-KIT remains as a clinical challenge due to limited effective treatment options for therapies. For example, the acquired activating point mutation D816V significantly impairs the efficacy of targeted cancer therapies. Understanding the mechanisms of drug resistance at the molecular level will aid in designing and developing particular inhibitors with the potential to overcome these resistance mutations. We undertake a structure-based de novo design of 7-azaindole as the molecular core using the modified scoring function. This approach led to an identification of new c-KIT inhibitors over 100-fold specific for the D816V mutant relative to the wild-type c-KIT with nanomolar inhibitory activity. More importantly, these compounds potently inhibit clinically relevant D816V mutations of c-KIT in biochemical and cellular studies.
• Identification of pharmacophore model, synthesis and biological evaluation of N-phenyl-1-arylamide and N-phenylbenzenesulfonamide derivatives as BACE 1 inhibitors
  作者：Wenhai Huang、Haiping Yu、Rong Sheng、Jia Li、Yongzhou Hu

  DOI：10.1016/j.bmc.2008.10.059

  日期：2008.12.15

  The pharmacophore model of arylpiperazine amide derivatives was built using Discovery Studio 2.0 software package and the best pharmacophore model ( Hypo 1) was validated by Enrichment and ROC method ( EF at 2%, 5% and 10% are 30.6, 12.2 and 7.7; AUC of the ROC curve is 0.93). According to the best pharmacophore model, 11 N-phenyl-1-arylamide, N-phenylbenzenesulfonamide derivatives, compounds 26-28, and 33a-g, were designed to be synthesized and their BACE 1 inhibitory activities were determined experimentally. Their theoretical results were in good agreement with the experimental values. Compound 33d, which displayed the highest BACE 1 activity (18.33 +/- 2.80 mu mol/L) among these two series, was chosen to study the protein binding pattern and the result showed that it was in close contact with two essential catalytic aspartates (Asp32 and Asp228) of the BACE 1. (C) 2008 Elsevier Ltd. All rights reserved.
• Dual-target-directed 1,3-diphenylurea derivatives: BACE 1 inhibitor and metal chelator against Alzheimer’s disease
  作者：Wenhai Huang、Dan Lv、Haiping Yu、Rong Sheng、Sun Chol Kim、Peng Wu、Kedi Luo、Jia Li、Yongzhou Hu

  DOI：10.1016/j.bmc.2010.06.042

  日期：2010.8

  Dual-target-directed 1,3-diphenylurea derivatives were designed by hybridizing BACE 1 inhibitor 1 with metal chelator LR-90. A database consisted of 1,3-diphenylurea derivatives was built and screened by the pharmacophore model (Hypo 1) of BACE 1 inhibitor. Based on the predicted results, 11 compounds (6a–d, 9a–g) with favorable Fitvalues were selected, synthesized and evaluated for their BACE 1 inhibitory

  通过将BACE 1抑制剂1与金属螯合剂LR-90杂交，设计了双靶标的1,3-二苯脲衍生物。建立了由1,3-二苯脲衍生物组成的数据库，并通过BACE 1抑制剂的药效团模型（Hypo 1）进行了筛选。根据预测结果，选择，合成了11种Fitfit值合适的化合物（6a - d，9a - g），并对其BACE 1抑制活性进行了评估，表明预测结果与实验值非常吻合。此外，合成的化合物还显示出螯合金属离子的能力。最有效的BACE 1抑制剂9f选择（27.85±2.46μmol/ L）进行进一步的受体结合研究，结果表明在9f的脲基团和催化天冬氨酸Asp228之间形成了必不可少的氢键。