1-(4-amino-6-methyl-1,3,5-triazin-2-yl)-N-(1-(difluoromethyl)-1H-pyrazol-3-yl)-1H-benzo[d]imidazol-2-amine | 1289169-48-7

• 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: 1-(4-amino-6-methyl-1,3,5-triazin-2-yl)-N-(1-(difluoromethyl)-1H-pyrazol-3-yl)-1H-benzo[d]imidazol-2-amine
• 英文别名: 1-(4-amino-6-methyl-1,3,5-triazin-2-yl)-N-[1-(difluoromethyl)pyrazol-3-yl]benzimidazol-2-amine
• CAS: 1289169-48-7
• 化学式: C₁₅H₁₃F₂N₉
• 分子量: 357.325
• InChiKey: BWVQDRRLGFHKGN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-chloro-1-(4-chloro-6-methyl-1,3,5-triazin-2-yl)-1H-benzo[d]imidazole 在 氨 作用下， 以 甲醇 、 仲丁醇 为溶剂， 生成 1-(4-amino-6-methyl-1,3,5-triazin-2-yl)-N-(1-(difluoromethyl)-1H-pyrazol-3-yl)-1H-benzo[d]imidazol-2-amine
  参考文献：
  名称：

  Discovery of triazine-benzimidazoles as selective inhibitors of mTOR

  摘要：

  mTOR is part of the PI3K/AKT pathway and is a central regulator of cell growth and survival. Since many cancers display mutations linked to the mTOR signaling pathway, mTOR has emerged as an important target for oncology therapy. Herein, we report the discovery of triazine benzimidazole inhibitors that inhibit mTOR kinase activity with up to 200-fold selectivity over the structurally homologous kinase PI3K alpha. When tested in a panel of cancer cell lines displaying various mutations, a selective inhibitor from this series inhibited cellular proliferation with a mean IC50 of 0.41 mu M. Lead compound 42 demonstrated up to 83% inhibition of mTOR substrate phosphorylation in a murine pharmacodynamic model. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.02.007

文献信息

• Discovery of triazine-benzimidazoles as selective inhibitors of mTOR
  作者：Emily A. Peterson、Paul S. Andrews、Xuhai Be、Alessandro A. Boezio、Tammy L. Bush、Alan C. Cheng、James R. Coats、Adria E. Colletti、Katrina W. Copeland、Michelle DuPont、Russell Graceffa、Barbara Grubinska、Jean-Christophe Harmange、Joseph L. Kim、Erin L. Mullady、Philip Olivieri、Laurie B. Schenkel、Mary K. Stanton、Yohannes Teffera、Douglas A. Whittington、Ti Cai、Daniel S. La

  DOI：10.1016/j.bmcl.2011.02.007

  日期：2011.4

  mTOR is part of the PI3K/AKT pathway and is a central regulator of cell growth and survival. Since many cancers display mutations linked to the mTOR signaling pathway, mTOR has emerged as an important target for oncology therapy. Herein, we report the discovery of triazine benzimidazole inhibitors that inhibit mTOR kinase activity with up to 200-fold selectivity over the structurally homologous kinase PI3K alpha. When tested in a panel of cancer cell lines displaying various mutations, a selective inhibitor from this series inhibited cellular proliferation with a mean IC50 of 0.41 mu M. Lead compound 42 demonstrated up to 83% inhibition of mTOR substrate phosphorylation in a murine pharmacodynamic model. (C) 2011 Elsevier Ltd. All rights reserved.