2-chloro-1-(4-chloro-[1,3,5]triazin-2-yl)-1H-benzimidazole | 333736-81-5

• 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: 2-chloro-1-(4-chloro-[1,3,5]triazin-2-yl)-1H-benzimidazole
• 英文别名: 2-chloro-1-(4-chloro-1,3,5-triazin-2-yl)benzimidazole
• CAS: 333736-81-5
• 化学式: C₁₀H₅Cl₂N₅
• 分子量: 266.089
• InChiKey: YKCLZJLGWVKMLR-UHFFFAOYSA-N

物化性质

• 沸点：
  543.7±33.0 °C(Predicted)
• 密度：
  1.70±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  56.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-chloro-1-(4-chloro-[1,3,5]triazin-2-yl)-1H-benzimidazole 在 氨 作用下， 以 甲醇 为溶剂， 生成
  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
• 作为产物：
  描述：

  2,4-二氯-1,3,5-三嗪 、 2-氯苯并咪唑 在 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 为溶剂， 生成 2-chloro-1-(4-chloro-[1,3,5]triazin-2-yl)-1H-benzimidazole
  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

• Substituted triazinyl amide derivatives and methods of use
  申请人：——

  公开号：US20030087908A1

  公开（公告）日：2003-05-08

  The invention encompasses compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions, uses and methods for prophylaxis and treatment of cancer and angiogenesis-related disease.

  本发明包括化合物、类似物、前药及其药物可接受的盐，药物组合物，以及用于预防与治疗癌症和与血管生成相关疾病的用途和方法。
• EP1385833A1
  申请人：——

  公开号：EP1385833A1

  公开（公告）日：2004-02-04
• US6864255B2
  申请人：——

  公开号：US6864255B2

  公开（公告）日：2005-03-08
• [EN] TRIAZINYL AMIDE DERIVATIVES AS ANGIOGENESIS INHIBITORS<br/>[FR] DERIVES D'AMIDE DE TRIAZINYLE UTILES EN TANT QU'INHIBITEURS DE ANGIOGENESE
  申请人：AMGEN INC

  公开号：WO2002083654A1

  公开（公告）日：2002-10-24

  The invention encompasses compounds of formula (I), analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical composition, uses and methods for prophylaxis and treatment of cancer and angiogenesis-related disease.
• 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.