2-(5-difluoromethoxy-6-fluoro-naphthalen-2-yl)-4,4,5,5-tetramethyl-[1,3,2]-dioxa borolane | 1426082-87-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-(5-difluoromethoxy-6-fluoro-naphthalen-2-yl)-4,4,5,5-tetramethyl-[1,3,2]-dioxa borolane
• CAS: 1426082-87-2
• 化学式: C₁₇H₁₈BF₃O₃
• 分子量: 338.134
• InChiKey: DOOBGMIDVDDESR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.88
• 重原子数：
  24.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  27.69
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  2-(5-difluoromethoxy-6-fluoro-naphthalen-2-yl)-4,4,5,5-tetramethyl-[1,3,2]-dioxa borolane 在 氢溴酸 、 palladium diacetate 、 potassium carbonate 、 溶剂黄146 、 三苯基膦 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 2.0h， 生成 6-{2-[4-(2-dimethylamino-ethoxy)-phenyl]-5-pyridin-4-yl-3H-imidazol-4-yl}-2-fluoro-naphthalen-1-ol trifluoroacetate
  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：

  5-溴茚酮 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 、 sodium fluoride 作用下， 以 邻二甲苯 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.33h， 生成 2-(5-difluoromethoxy-6-fluoro-naphthalen-2-yl)-4,4,5,5-tetramethyl-[1,3,2]-dioxa borolane
  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