2-[3-({2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazol-4-yl}oxy)propyl]-1H-isoindole-1,3(2H)-dione | 1246548-05-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-[3-({2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazol-4-yl}oxy)propyl]-1H-isoindole-1,3(2H)-dione
• 英文别名: 2-[3-[2-(Difluoromethyl)-1-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)benzimidazol-4-yl]oxypropyl]isoindole-1,3-dione；2-[3-[2-(difluoromethyl)-1-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)benzimidazol-4-yl]oxypropyl]isoindole-1,3-dione
• CAS: 1246548-05-9
• 化学式: C₃₀H₃₀F₂N₈O₅
• 分子量: 620.616
• InChiKey: MJUIRQJCVZBSEM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  45
• 可旋转键数：
  9
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  128
• 氢给体数：
  0
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  2-[3-({2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazol-4-yl}oxy)propyl]-1H-isoindole-1,3(2H)-dione 在 一水合肼 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 24.0h， 以28%的产率得到3-({2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazol-4-yl}oxy)-1-propanamine
  参考文献：
  名称：

  Synthesis and biological evaluation of novel phosphatidylinositol 3-kinase inhibitors: Solubilized 4-substituted benzimidazole analogs of 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474)

  摘要：

  A range of 4-substituted derivatives of the pan class I PI 3-kinase inhibitor 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474) were prepared in a search for more soluble analogs. 4-Aminoalkoxy substituents provided the most potent derivatives, with the 4-O(CH2)(3)NMe2 analog (compound 14) being identified as displaying the best overall activity in combination with good aqueous solubility (25 mg/mL for the hydrochloride salt). This compound was tested in a U87MG xenograft model, but displayed less potency than ZSTK474 as a result of an unfavorable pharmacokinetic profile. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.03.038
• 作为产物：
  描述：

  2-(difluoromethyl)-4-hydroxy-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole 、 N-(3-溴丙基)苯二胺 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.5h， 以96%的产率得到2-[3-({2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazol-4-yl}oxy)propyl]-1H-isoindole-1,3(2H)-dione
  参考文献：
  名称：

  Synthesis and biological evaluation of novel phosphatidylinositol 3-kinase inhibitors: Solubilized 4-substituted benzimidazole analogs of 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474)

  摘要：

  A range of 4-substituted derivatives of the pan class I PI 3-kinase inhibitor 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474) were prepared in a search for more soluble analogs. 4-Aminoalkoxy substituents provided the most potent derivatives, with the 4-O(CH2)(3)NMe2 analog (compound 14) being identified as displaying the best overall activity in combination with good aqueous solubility (25 mg/mL for the hydrochloride salt). This compound was tested in a U87MG xenograft model, but displayed less potency than ZSTK474 as a result of an unfavorable pharmacokinetic profile. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.03.038