{2-[4-(4-bromo-5-pyridin-4-yl-1H-imidazol-2-yl)-phenoxy]-ethyl}-dimethyl-amine | 1251931-23-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: {2-[4-(4-bromo-5-pyridin-4-yl-1H-imidazol-2-yl)-phenoxy]-ethyl}-dimethyl-amine
• 英文别名: 2-[4-(5-bromo-4-pyridin-4-yl-1H-imidazol-2-yl)phenoxy]-N,N-dimethylethanamine
• CAS: 1251931-23-3
• 化学式: C₁₈H₁₉BrN₄O
• 分子量: 387.279
• InChiKey: IWDHVUKMCPFDIG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  54
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  {2-[4-(4-bromo-5-pyridin-4-yl-1H-imidazol-2-yl)-phenoxy]-ethyl}-dimethyl-amine 、 3-氯-4-氟苯硼酸 在 palladium diacetate 、 potassium carbonate 、 三苯基膦 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 2.0h， 以7%的产率得到(2-{4-[5-(3-chloro-4-fluoro-phenyl)-4-pyridin-4-yl-1H-imidazol-2-yl]-phenoxy}-ethyl)-dimethyl-amine
  参考文献：
  名称：

  Potent BRAF kinase inhibitors based on 2,4,5-trisubstituted imidazole with naphthyl and benzothiophene 4-substituents

  摘要：

  The RAS-RAF-MEK-ERK pathway is hyperactivated in 30% of human cancers. BRAF is a serine-threonine kinase, belonging to this pathway that is mutated with high frequency in human melanoma and other cancers thus BRAF is an important therapeutic target in melanoma. We have designed inhibitors of BRAF based on 2,4,5-trisubstituted imidazoles with naphthyl and benzothiophene-4-substituents. Two compounds were discovered to be potent BRAF inhibitors: 1-(6-{2-[4-(2-dimethylamino-ethoxy) phenyl]-5-(pyridin-4-yl)-1H-imidazol-4-yl} benzo[b]thiophen-3-yl)-2,2,2-trifluoroethanol (1i) with BRAF IC50 = 190 nM and with cellular GI(50) = 2100 nM, and 6-{2-[4-(2-dimethylamino-ethoxy)-phenyl]-5-pyridin-4-yl-3H-imidazol-4-yl}-naphthalen-1-ol (1q) with IC50 = 9 nM and GI(50) = 220 nM. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.12.035
• 作为产物：
  描述：

  {2-[4-(4-bromo-1-methoxymethyl-5-pyridin-4-yl-1H-imidazol-2-yl)-phenoxy]-ethyl}-dimethyl-amine 在 盐酸 、 水 作用下， 生成 {2-[4-(4-bromo-5-pyridin-4-yl-1H-imidazol-2-yl)-phenoxy]-ethyl}-dimethyl-amine
  参考文献：
  名称：

  Potent BRAF kinase inhibitors based on 2,4,5-trisubstituted imidazole with naphthyl and benzothiophene 4-substituents

  摘要：

  The RAS-RAF-MEK-ERK pathway is hyperactivated in 30% of human cancers. BRAF is a serine-threonine kinase, belonging to this pathway that is mutated with high frequency in human melanoma and other cancers thus BRAF is an important therapeutic target in melanoma. We have designed inhibitors of BRAF based on 2,4,5-trisubstituted imidazoles with naphthyl and benzothiophene-4-substituents. Two compounds were discovered to be potent BRAF inhibitors: 1-(6-{2-[4-(2-dimethylamino-ethoxy) phenyl]-5-(pyridin-4-yl)-1H-imidazol-4-yl} benzo[b]thiophen-3-yl)-2,2,2-trifluoroethanol (1i) with BRAF IC50 = 190 nM and with cellular GI(50) = 2100 nM, and 6-{2-[4-(2-dimethylamino-ethoxy)-phenyl]-5-pyridin-4-yl-3H-imidazol-4-yl}-naphthalen-1-ol (1q) with IC50 = 9 nM and GI(50) = 220 nM. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.12.035

文献信息

• [EN] RAF KINASE INHIBITORS<br/>[FR] INHIBITEURS DE LA KINASE RAF
  申请人：SELEXAGEN THERAPEUTICS INC

  公开号：WO2011085269A1

  公开（公告）日：2011-07-14

  Described herein are compounds, pharmaceutical compositions and methods for the inhibition of RAF kinae mediated signaling. Said compounds, pharmaceutical compositions and methods have utility in the treatment of human disease and disorders.

  本文描述了用于抑制RAF激酶介导信号的化合物、药物组合物和方法。这些化合物、药物组合物和方法在治疗人类疾病和疾病方面具有实用性。
• RAF KINASE INHIBITORS
  申请人：Vernier Jean-Michel

  公开号：US20130040983A1

  公开（公告）日：2013-02-14

  Described herein are compounds, pharmaceutical compositions and methods for the inhibition of RAF kinae mediated signaling. Said compounds, pharmaceutical compositions and methods have utility in the treatment of human disease and disorders.

  本文介绍了一些化合物、药物组合物和方法，用于抑制RAF激酶介导的信号传导。这些化合物、药物组合物和方法在治疗人类疾病和疾病方面具有实用性。