1-(4-amino-6-methyl-1,3,5-triazin-2-yl)-N-1H-indol-6-yl-1H-benzimidazol-2-amine | 1239978-79-0

• 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-1H-indol-6-yl-1H-benzimidazol-2-amine
• 英文别名: 1-(4-amino-6-methyl-1,3,5-triazin-2-yl)-N-(1H-indol-6-yl)-1H-benzo[d]imidazol-2-amine；1-(4-amino-6-methyl-1,3,5-triazin-2-yl)-N-(1H-indol-6-yl)benzimidazol-2-amine
• CAS: 1239978-79-0
• 化学式: C₁₉H₁₆N₈
• 分子量: 356.39
• InChiKey: BFUAMEMDRSZWDZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  110
• 氢给体数：
  3
• 氢受体数：
  6

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-1H-indol-6-yl-1H-benzimidazol-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

• [EN] INDOLE/BENZIMIDAZOLE COMPOUNDS AS mTOR KINASE INHIBITORS<br/>[FR] COMPOSÉS D'INDOLE OU BENZIMIDAZOLE CONVENANT COMME INHIBITEURS DE LA KINASE MTOR
  申请人：AMGEN INC

  公开号：WO2010096314A1

  公开（公告）日：2010-08-26

  The present invention provides compounds that are kinase inhibitors, specifically PIK kinase inhibitors, more specifically, mTOR inhibitors and are therefore useful for the treatment of diseases treatable by inhibition of kinases, specifically PIK kinase inhibitors, more specifically, mTOR such as cancer. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

  本发明提供了一种激酶抑制剂化合物，具体来说是PIK激酶抑制剂，更具体地说是mTOR抑制剂，因此适用于治疗通过抑制激酶治疗的疾病，特别是PIK激酶抑制剂，更具体地说是mTOR抑制剂，例如癌症。还提供了含有这些化合物的药物组合物和制备这些化合物的方法。
• Indole/Benzimidazole Compounds as mTOR Kinase Inhibitors
  申请人：Boezio Alessandro

  公开号：US20120165334A1

  公开（公告）日：2012-06-28

  The present invention provides compounds that are kinase inhibitors, specifically PIK kinase inhibitors, more specifically, mTOR inhibitors and are therefore useful for the treatment of diseases treatable by inhibition of kinases, specifically PIK kinase inhibitors, more specifically, mTOR such as cancer. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

  本发明提供了一种激酶抑制剂，具体地说是PIK激酶抑制剂，更具体地说是mTOR抑制剂，因此适用于治疗通过抑制激酶，特别是PIK激酶抑制剂，更具体地说是mTOR抑制剂可治疗的疾病，例如癌症。还提供了含有这种化合物的药物组合物和制备这种化合物的方法。
• INDOLE/BENZIMIDAZOLE COMPOUNDS AS mTOR KINASE INHIBITORS
  申请人：Amgen, Inc

  公开号：EP2398791A1

  公开（公告）日：2011-12-28
• [EN] COMPOUNDS AND COMPOSITIONS FOR TREATING CONDITIONS ASSOCIATED WITH STING ACTIVITY<br/>[FR] COMPOSÉS ET COMPOSITIONS POUR TRAITER DES ÉTATS PATHOLOGIQUES ASSOCIÉS À UNE ACTIVITÉ DE STING
  申请人：IFM DUE INC

  公开号：WO2022133098A2

  公开（公告）日：2022-06-23

  [EN] This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt, and/or hydrate, and/or cocrystal, and/or drug combination of the compound) that inhibit (e.g., antagonize) Stimulator of Interferon Genes (STING). Said chemical entities are useful, e.g., for treating a condition, disease or disorder in which increased (e.g., excessive) STING activation (e.g., STING signaling) contributes to the pathology and/or symptoms and/or progression of the condition, disease or disorder (e.g., cancer) in a subject (e.g., a human). This disclosure also features compositions containing the same as well as methods of using and making the same.
  [FR] La présente divulgation concerne des entités chimiques (par exemple, un composé ou un sel, et/ou un hydrate, et/ou un co-cristal et/ou une combinaison de médicament du composé pharmaceutiquement acceptables) qui inhibent (par exemple, antagonisent) le stimulateur des gènes de l'interféron (STING). Lesdites entités chimiques sont utiles, par exemple, pour traiter un état pathologique, une maladie ou un trouble dans lequel une activation accrue (par exemple, excessive) de STING (par exemple, une signalisation de STING) contribue à la pathologie et/ou aux symptômes et/ou à la progression de l'état pathologique, de la maladie ou du trouble (par exemple, le cancer) chez un sujet (par exemple, un humain). La divulgation concerne également des compositions les contenant, ainsi que des procédés d'utilisation et de fabrication de celles-ci.
• 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.