4-(3-{[tert-butyl(dimethyl)silyl]oxy}propoxy)-2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole | 1246548-03-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 4-(3-{[tert-butyl(dimethyl)silyl]oxy}propoxy)-2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole
• 英文别名: Tert-butyl-[3-[2-(difluoromethyl)-1-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)benzimidazol-4-yl]oxypropoxy]-dimethylsilane；tert-butyl-[3-[2-(difluoromethyl)-1-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)benzimidazol-4-yl]oxypropoxy]-dimethylsilane
• CAS: 1246548-03-7
• 化学式: C₂₈H₄₁F₂N₇O₄Si
• 分子量: 605.76
• InChiKey: RECWKNBPWQVNPI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.61
• 重原子数：
  42
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  99.9
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  4-(3-{[tert-butyl(dimethyl)silyl]oxy}propoxy)-2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以81%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-propanol
  参考文献：
  名称：

  [EN] PYRIMIDINYL AND 1,3,5 TRIAZINYL BENZIMIDAZOLES AND THEIR USE IN CANCER THERAPY
  [FR] PYRIMIDINYL ET 1,3,5-TRIAZINYL BENZIMIDAZOLES ET LEUR UTILISATION EN THÉRAPIE ANTICANCÉREUSE

  摘要：

  本文提供了嘧啶基和1,3,5-三嗪基苯并唑类化合物，以及它们的药物组合、制备方法，以及作为抗癌治疗药物或药剂的用途，可以单独使用，也可以与放疗和/或其他抗癌药物联合使用。

  公开号：

  WO2010110686A1
• 作为产物：
  描述：

  2-氨基-3-硝基苯酚 在 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 作用下， 以 吡啶 、 甲醇 、 二甲基亚砜 、 丙酮 为溶剂， 反应 32.0h， 生成 4-(3-{[tert-butyl(dimethyl)silyl]oxy}propoxy)-2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole
  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

文献信息

• [EN] PYRIMIDINYL AND 1,3,5 TRIAZINYL BENZIMIDAZOLES AND THEIR USE IN CANCER THERAPY<br/>[FR] PYRIMIDINYL ET 1,3,5-TRIAZINYL BENZIMIDAZOLES ET LEUR UTILISATION EN THÉRAPIE ANTICANCÉREUSE
  申请人：PATHWAY THERAPEUTICS LTD

  公开号：WO2010110686A1

  公开（公告）日：2010-09-30

  Provided herein are pyrimidinyl and 1,3,5-triazinyl benzimidazoles, and their pharmaceutical compositions, preparation, and use as agents or drugs for cancer therapy, either alone or in combination with radiation and/or other anticancer drugs.

  本文提供了嘧啶基和1,3,5-三嗪基苯并唑类化合物，以及它们的药物组合、制备方法，以及作为抗癌治疗药物或药剂的用途，可以单独使用，也可以与放疗和/或其他抗癌药物联合使用。
• 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)
  作者：Gordon W. Rewcastle、Swarna A. Gamage、Jack U. Flanagan、Jackie D. Kendall、William A. Denny、Bruce C. Baguley、Christina M. Buchanan、Mindy Chao、Philip Kestell、Sharada Kolekar、Woo-Jeong Lee、Claire L. Lill、Alisha Malik、Ripudaman Singh、Stephen M.F. Jamieson、Peter R. Shepherd

  DOI：10.1016/j.ejmech.2013.03.038

  日期：2013.6

  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.