(2-{4-[4-(6-fluoro-naphthalen-2-yl)-1-methoxymethyl-5-pyridin-4-yl-1H-imidazol-2-yl]-phenoxy}-ethyl)-dimethyl-amine | 1426083-09-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (2-{4-[4-(6-fluoro-naphthalen-2-yl)-1-methoxymethyl-5-pyridin-4-yl-1H-imidazol-2-yl]-phenoxy}-ethyl)-dimethyl-amine
• CAS: 1426083-09-1
• 化学式: C₃₀H₂₉FN₄O₂
• 分子量: 496.584
• InChiKey: ULEPJDTYJBFVJV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.12
• 重原子数：
  37.0
• 可旋转键数：
  9.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  52.41
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (2-{4-[4-(6-fluoro-naphthalen-2-yl)-1-methoxymethyl-5-pyridin-4-yl-1H-imidazol-2-yl]-phenoxy}-ethyl)-dimethyl-amine 在 盐酸 、 水 作用下， 反应 1.0h， 以70%的产率得到(2-{4-[5-(6-fluoro-naphthalen-2-yl)-4-pyridin-4-yl-1H-imidazol-2-yl]-phenoxy}-ethyl)-dimethyl-amine hydrochloride
  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-溴-6-氟萘 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 、 palladium diacetate 、 potassium carbonate 、 三苯基膦 作用下， 以 乙二醇二甲醚 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 (2-{4-[4-(6-fluoro-naphthalen-2-yl)-1-methoxymethyl-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