1-(4-{[2-({6-[1-(cyclopropylmethyl)-1H-pyrazol-4-yl]-1H-benzimidazol-2-yl}amino)pyridin-4-yl]methyl}piperazin-1-yl)-3,3,3-trifluoropropan-1-one

• 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-{[2-({6-[1-(cyclopropylmethyl)-1H-pyrazol-4-yl]-1H-benzimidazol-2-yl}amino)pyridin-4-yl]methyl}piperazin-1-yl)-3,3,3-trifluoropropan-1-one
• 英文别名: 1-[4-[[2-[[6-[1-(cyclopropylmethyl)pyrazol-4-yl]-1H-benzimidazol-2-yl]amino]pyridin-4-yl]methyl]piperazin-1-yl]-3,3,3-trifluoropropan-1-one
• 化学式: C₂₇H₂₉F₃N₈O
• 分子量: 538.575
• InChiKey: SSMPZXRXMBEUFU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  39
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  95
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  3,3,3-三氟丙酸 、 6-[1-(cyclopropylmethyl)-1H-pyrazol-4-yl]-N-{4-[(piperazin-1-yl)methyl]pyridin-2-yl}-1H-benzimidazol-2-amine hydrochloride 在 碳酸氢钠 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以56 %的产率得到1-(4-{[2-({6-[1-(cyclopropylmethyl)-1H-pyrazol-4-yl]-1H-benzimidazol-2-yl}amino)pyridin-4-yl]methyl}piperazin-1-yl)-3,3,3-trifluoropropan-1-one
  参考文献：
  名称：

  Discovery of BAY-985, a Highly Selective TBK1/IKKε Inhibitor

  摘要：

  The serine/threonine kinase TBK1 (TANK-binding kinase 1) and its homologue IKK epsilon are noncanonical members of the inhibitor of the nuclear factor kappa B (I kappa B) kinase family. These kinases play important roles in multiple cellular pathways and, in particular, in inflammation. Herein, we describe our investigations on a family of benzimidazoles and the identification of the potent and highly selective TBK1/IKK epsilon inhibitor BAY-985. BAY-985 inhibits the cellular phosphorylation of interferon regulatory factor 3 and displays antiproliferative efficacy in the melanoma cell line SK-MEL-2 but showed only weak antitumor activity in the SK-MEL-2 human melanoma xenograft model.

  DOI：

  10.1021/acs.jmedchem.9b01460

文献信息

• [EN] HETEROARYLBENZIMIDAZOLE COMPOUNDS<br/>[FR] COMPOSÉS HÉTÉROARYLBENZIMIDAZOLE
  申请人：BAYER PHARMA AG

  公开号：WO2017102091A1

  公开（公告）日：2017-06-22

  The present invention covers heteroarylbenzimidazole compounds of general formula (I) in which R1, R2, R3, R4 and R5 are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of hyperproliferative and/or inflammatory disorders, as a sole agent or in combination with other active ingredients.

  本发明涵盖了一般式（I）中的杂环芳基苯并咪唑化合物，其中R1、R2、R3、R4和R5如本文所定义，制备所述化合物的方法，用于制备所述化合物的有用中间体化合物，包括所述化合物的药物组合物和组合物，以及利用所述化合物制造用于治疗或预防疾病的药物组合物，特别是治疗或预防过度增殖和/或炎症性疾病的药物组合物，作为唯一活性成分或与其他活性成分组合使用。
• Heteroarylbenzimidazole compounds
  申请人：BAYER PHARMA AKTIENGESELLSCHAFT

  公开号：US10894784B2

  公开（公告）日：2021-01-19

  The present invention covers heteroarylbenzimidazole compounds of general formula (I) in which R1, R2, R3, R4 and R5 are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of hyperproliferative and/or inflammatory disorders, as a sole agent or in combination with other active ingredients.

  本发明涉及通式（I）的杂芳基苯并咪唑化合物（其中 R1、R2、R3、R4 和 R5 如本文所定义）、制备所述化合物的方法、用于制备所述化合物的中间体化合物、包含所述化合物的药物组合物和组合物，以及使用所述化合物制造药物组合物，用于治疗或预防疾病，特别是过度增殖性疾病和/或炎症性疾病，作为单独制剂或与其他活性成分组合使用。
• HETEROARYLBENZIMIDAZOLE COMPOUNDS
  申请人：Bayer Pharma Aktiengesellschaft

  公开号：EP3390387A1

  公开（公告）日：2018-10-24
• Discovery of BAY-985, a Highly Selective TBK1/IKKε Inhibitor
  作者：Julien Lefranc、Volker Klaus Schulze、Roman Christian Hillig、Hans Briem、Florian Prinz、Anne Mengel、Tobias Heinrich、Jozsef Balint、Srinivasan Rengachari、Horst Irlbacher、Detlef Stöckigt、Ulf Bömer、Benjamin Bader、Stefan Nikolaus Gradl、Carl Friedrich Nising、Franz von Nussbaum、Dominik Mumberg、Daniel Panne、Antje Margret Wengner

  DOI：10.1021/acs.jmedchem.9b01460

  日期：2020.1.23

  The serine/threonine kinase TBK1 (TANK-binding kinase 1) and its homologue IKK epsilon are noncanonical members of the inhibitor of the nuclear factor kappa B (I kappa B) kinase family. These kinases play important roles in multiple cellular pathways and, in particular, in inflammation. Herein, we describe our investigations on a family of benzimidazoles and the identification of the potent and highly selective TBK1/IKK epsilon inhibitor BAY-985. BAY-985 inhibits the cellular phosphorylation of interferon regulatory factor 3 and displays antiproliferative efficacy in the melanoma cell line SK-MEL-2 but showed only weak antitumor activity in the SK-MEL-2 human melanoma xenograft model.