6-[2-(2,6-difluoro-phenyl)-5-phenyl-1H-imidazol-4-yl]-1-(propane-2-sulfonyl)-1H-benzoimidazol-2-ylamine | 660433-80-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 6-[2-(2,6-difluoro-phenyl)-5-phenyl-1H-imidazol-4-yl]-1-(propane-2-sulfonyl)-1H-benzoimidazol-2-ylamine
• 英文别名: 479754；1-isopropylsulfonyl-2-amino-6-(2-(2,6-difluorophenyl)-5-(phenyl)-imidazol-4-yl)-benzimidazole；6-[2-(2,6-difluorophenyl)-5-phenyl-1H-imidazol-4-yl]-1-propan-2-ylsulfonylbenzimidazol-2-amine
• CAS: 660433-80-7
• 化学式: C₂₅H₂₁F₂N₅O₂S
• 分子量: 493.537
• InChiKey: NQPPPAJKEZYMMP-UHFFFAOYSA-N

物化性质

• 熔点：
  193 °C
• 沸点：
  729.1±70.0 °C(Predicted)
• 密度：
  1.45±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-[2-(2,6-difluoro-phenyl)-5-phenyl-1H-imidazol-4-yl]-1-(propane-2-sulfonyl)-1H-benzoimidazol-2-ylamine 在 亚硝酸特丁酯 、 copper(l) chloride 作用下， 生成 C₂₅H₁₉ClF₂N₄O₂S
  参考文献：
  名称：

  Imidazolyl benzimidazoles and imidazo[4,5-b]pyridines as potent p38α MAP kinase inhibitors with excellent in vivo antiinflammatory properties

  摘要：

  Herein we report investigations into the p38 alpha MAP kinase activity of trisubstituted imidazoles that led to the identification of compounds possessing highly potent in vivo activity. The SAR of a novel series of imidazopyridines is demonstrated as well, resulting in compounds possessing cellular potency and enhanced in vivo activity in the rat collagen-induced arthritis model of chronic inflammation. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.10.106
• 作为产物：
  描述：

  6-(phenylethynyl)-1-(propane-2-sulfonyl)-1H-benzimidazol-2-ylamine 在 potassium permanganate 、 ammonium acetate 、 碳酸氢钠 、 magnesium sulfate 作用下， 以 丙酮 、 正丁醇 为溶剂， 反应 1.0h， 生成 6-[2-(2,6-difluoro-phenyl)-5-phenyl-1H-imidazol-4-yl]-1-(propane-2-sulfonyl)-1H-benzoimidazol-2-ylamine
  参考文献：
  名称：

  具有有效的体内功效的有效和选择性的基于2-氨基苯并咪唑的p38alpha MAP激酶抑制剂的设计。

  摘要：

  我们报告了基于2-氨基苯并咪唑的有效和高度选择性的p38alphainhibitors系列的设计和发现。铅化合物1在ATP竞争性酶结合和巨噬细胞中的TNFα释放抑制方面均具有低纳摩尔活性。与其他p38参考化合物相比，化合物18在大鼠胶原蛋白诱发的关节炎模型中显示出出色的药代动力学特性和口服活性。还介绍了解决CyP3A4责任的SAR策略。

  DOI：

  10.1021/jm048978k

文献信息

• [EN] BENZIMIDAZOLES AND BENZOTHIAZOLES AS INHIBITORS OF MAP KINASE<br/>[FR] BENZIMIDAZOLES ET BENZOTHIAZOLES UTILISES COMME INHIBITEURS DE LA MAP KINASE
  申请人：LILLY CO ELI

  公开号：WO2004014900A1

  公开（公告）日：2004-02-19

  The present invention provides kinase inhibitors of Formula I: wherein W represents inter alia imidazol, oxazol, pyrazol, thiazol as triazol, which are substituted by phenyl or thienyl. The disclosed compounds inhibit p-38 kinase and are useful in the treatment of metastasis or rheumatoid arthritis.

  本发明提供了一种化合物I的激酶抑制剂：其中W代表咪唑、噁唑、吡唑、噻唑或三唑等，这些化合物被苯基或噻吩基取代。所公开的化合物抑制p-38激酶，在转移或类风湿性关节炎的治疗中很有用。
• Benzimidazoles and benzothiazoles as inhibitors of map kinase
  申请人：Bonjouklian Rosanne

  公开号：US20050272791A1

  公开（公告）日：2005-12-08

  The present invention provides kinase inhibitors of Formula I: wherein W represents inter alia imidazol, oxazol, pyrazol, thiazol as triazol, which are substituted by phenyl or thienyl. The disclosed compounds inhibit p-38 kinase and are useful in the treatment of metastasis or rheumatoid arthritis.

  本发明提供了式I的激酶抑制剂：其中W代表咪唑、噁唑、吡唑、噻唑或三唑等，它们被苯基或噻吩基取代。所披露的化合物抑制p-38激酶，在治疗转移或类风湿性关节炎方面有用。
• Medicament for treatment of liver cancer
  申请人：Zender Lars

  公开号：US10441577B2

  公开（公告）日：2019-10-15

  The invention provides a pharmaceutical composition comprising Sorafenib in combination with an inhibitor of a specific kinase inhibitor as a medicament for the treatment or prevention of liver cancer.

  本发明提供了一种药物组合物，该组合物由索拉非尼与一种特异性激酶抑制剂组合而成，作为治疗或预防肝癌的药物。
• Synthesis of Imidazole Based p38 MAP (Mitogen-Activated Protein) Kinase Inhibitors under Buffered Conditions
  作者：Nicholas A. Magnus、William D. Diseroad、C. Richard Nevill、James P. Wepsiec

  DOI：10.1021/op060042t

  日期：2006.5.1

  This article describes chemistry that was developed to give access to multigram quantities of imidazole 479754 and several related analogues for Eli Lilly's p38 MAPK program targeting therapies to address inflammation. The molecules of interest have an isopropyl sulfonyl group present on the 2-aminobenzimidazole heterocycyle that was found to be labile when heated in polar solvents and/or exposed to high or low pH. Due to this instability issue, the syntheses of the target molecules required optimizing Sonogashira reaction conditions, employing a buffered oxidative method to produce alpha-diones, developing buffered reaction conditions to generate imidazoles, and developing final recrystallization conditions.
• BENZIMIDAZOLES AND BENZOTHIAZOLES AS INHIBITORS OF MAP KINASE
  申请人：ELI LILLY AND COMPANY

  公开号：EP1554272B1

  公开（公告）日：2006-10-25