1-(4-{1-[2-({6-[1-(cyclopropylmethyl)-1H-pyrazol-4-yl]-1H-benzimidazol-2-yl}amino)pyridin-4-yl]ethyl}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-{1-[2-({6-[1-(cyclopropylmethyl)-1H-pyrazol-4-yl]-1H-benzimidazol-2-yl}amino)pyridin-4-yl]ethyl}piperazin-1-yl)-3,3,3-trifluoropropan-1-one
• 英文别名: 1-[4-[(1~{R})-1-[2-[[5-[1-(cyclopropylmethyl)pyrazol-4-yl]-1~{H}-benzimidazol-2-yl]amino]pyridin-4-yl]ethyl]piperazin-1-yl]-3,3,3-tris(fluoranyl)propan-1-one；1-[4-[(1R)-1-[2-[[6-[1-(cyclopropylmethyl)pyrazol-4-yl]-1H-benzimidazol-2-yl]amino]pyridin-4-yl]ethyl]piperazin-1-yl]-3,3,3-trifluoropropan-1-one
• 化学式: C₂₈H₃₁F₃N₈O
• 分子量: 552.602
• InChiKey: WEFRCKPVMWDRAK-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  40
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.43
• 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-[(1R)-1-(piperazin-1-yl)ethyl]pyridin-2-yl}-1Hbenzimidazol-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44 %的产率得到1-(4-{1-[2-({6-[1-(cyclopropylmethyl)-1H-pyrazol-4-yl]-1H-benzimidazol-2-yl}amino)pyridin-4-yl]ethyl}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

• 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.