1-(2-(trifluoromethyl)phenyl)-1H-imidazole-4-carbonitrile

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(2-(trifluoromethyl)phenyl)-1H-imidazole-4-carbonitrile
• 英文别名: 2-(trifluoromethyl)phenyl-1H-imidazole-4-carbonitrile；1-[2-(trifluoromethyl)phenyl]imidazole-4-carbonitrile
• 化学式: C₁₁H₆F₃N₃
• 分子量: 237.184
• InChiKey: APFBHMLJTFDXKT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  41.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(2-(trifluoromethyl)phenyl)-1H-imidazole-4-carbonitrile 在 titanium(IV) isopropylate 作用下， 以 乙醚 、 二氯甲烷 、 甲苯 为溶剂， 反应 13.75h， 生成 (R)-4-((S)-1-fluoroethyl)-3-(2-((1-(1-(2-(trifluoromethyl)phenyl)-1H-imidazol-4-yl)cyclopropyl)amino)pyrimidin-4-yl)oxazolidin-2-one
  参考文献：
  名称：

  Discovery and structure-activity-relationship study of novel imidazole cyclopropyl amine analogues for mutant isocitric dehydrogenase 1 (IDH1) inhibitors

  摘要：

  The discovery and optimization of imidazole cyclopropyl amime analogues as mutant IDH1 inhibitors via structure-based rational design were reported. The optimal compounds demonstrated both potent inhibition in IDH1(R132H) enzymatic activity and 2HG production in IDH1 mutant HT1080 cell line, moderate liver microsome stability and PK properties.

  DOI：

  10.1016/j.bmcl.2018.07.002
• 作为产物：
  描述：

  2-碘三氟甲基苯 、 1H-咪唑-4-甲腈 在 copper(l) iodide 、 (1R,2R)-(-)-N,N'-二甲基-1,2-环己二胺 、 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 1-(2-(trifluoromethyl)phenyl)-1H-imidazole-4-carbonitrile
  参考文献：
  名称：

  Discovery and structure-activity-relationship study of novel imidazole cyclopropyl amine analogues for mutant isocitric dehydrogenase 1 (IDH1) inhibitors

  摘要：

  The discovery and optimization of imidazole cyclopropyl amime analogues as mutant IDH1 inhibitors via structure-based rational design were reported. The optimal compounds demonstrated both potent inhibition in IDH1(R132H) enzymatic activity and 2HG production in IDH1 mutant HT1080 cell line, moderate liver microsome stability and PK properties.

  DOI：

  10.1016/j.bmcl.2018.07.002

文献信息

• LXR and FXR Modulators
  申请人：Boren Brant Clayton

  公开号：US20100069367A1

  公开（公告）日：2010-03-18

  Compounds of the invention are disclosed, such as compounds of formulae LX-LXIV, and pharmaceutically acceptable salts, isomers, or prodrugs thereof, which are useful as modulators of the activity of liver X receptors (LXR) and Farnesoid X receptors (FXR), where R 00 , R 200 , R 400 , R 500 , J 11 , J 21 , G 1 , G 21 , and Q are defined herein. Pharmaceutical compositions containing the compounds and methods of using the compounds are also disclosed.

  本发明揭示了化合物，例如公式LX-LXIV的化合物，以及其药学上可接受的盐、异构体或前药，这些化合物对于肝X受体（LXR）和法尼索叶酸X受体（FXR）的活性调节有用，其中R00、R200、R400、R500、J11、J21、G1、G21和Q在此处被定义。还揭示了含有这些化合物的药物组合物和使用这些化合物的方法。
• LXR and FXR modulators
  申请人：Exelixis Patent Company LLC

  公开号：US07998995B2

  公开（公告）日：2011-08-16

  Compounds of the invention are disclosed, such as compounds of formulae LX-LXIV, and pharmaceutically acceptable salts, isomers, or prodrugs thereof, which are useful as modulators of the activity of liver X receptors (LXR) and Farnesoid X receptors (FXR), where R00, R200, R400, R500, J11, J21, G1, G21, and Q are defined herein. Pharmaceutical compositions containing the compounds and methods of using the compounds are also disclosed.

  本发明揭示了化合物，例如公式LX-LXIV的化合物，以及其药学上可接受的盐、异构体或前药，它们有用于调节肝X受体（LXR）和法尼索受体（FXR）活性的作用，其中R00、R200、R400、R500、J11、J21、G1、G21和Q在此定义。还揭示了含有这些化合物的制药组合物和使用这些化合物的方法。
• Discovery and structure-activity-relationship study of novel imidazole cyclopropyl amine analogues for mutant isocitric dehydrogenase 1 (IDH1) inhibitors
  作者：Qiangang Zheng、Ziqi Chen、Huixin Wan、Shuai Tang、Yan Ye、Yuan Xu、Lei Jiang、Jian Ding、Meiyu Geng、Min Huang、Ying Huang

  DOI：10.1016/j.bmcl.2018.07.002

  日期：2018.12

  The discovery and optimization of imidazole cyclopropyl amime analogues as mutant IDH1 inhibitors via structure-based rational design were reported. The optimal compounds demonstrated both potent inhibition in IDH1(R132H) enzymatic activity and 2HG production in IDH1 mutant HT1080 cell line, moderate liver microsome stability and PK properties.