1-(5-fluoro-2-hydroxybenzyl)-3-(3-t-butyl-1-p-tolyl-1H-pyrazol-5-yl)urea | 940875-04-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(5-fluoro-2-hydroxybenzyl)-3-(3-t-butyl-1-p-tolyl-1H-pyrazol-5-yl)urea
• 英文别名: 1-(5-fluoro2-hydroxybenzyl)-3-(3-t-butyl-1-p-tolyl-1H-pyrazol-5-yl)urea；1-[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]-3-[(5-fluoro-2-hydroxyphenyl)methyl]urea
• CAS: 940875-04-7
• 化学式: C₂₂H₂₅FN₄O₂
• 分子量: 396.465
• InChiKey: AVYJNINNOYUMBS-UHFFFAOYSA-N

物化性质

• 沸点：
  544.4±50.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  79.2
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(5-fluoro-2-hydroxybenzyl)-3-(3-t-butyl-1-p-tolyl-1H-pyrazol-5-yl)urea 在 sodium carbonate 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 丙酮 为溶剂， 生成 1-(2-(2-morpholinopyrimidin-4-yloxy)-5-fluorobenzyl)-3-(3-t-butyl-1-p-tolyl-1H-pyrazol-5-yl)urea
  参考文献：
  名称：

  Design and synthesis of novel p38α MAP kinase inhibitors: Discovery of pyrazole-benzyl ureas bearing 2-molpholinopyrimidine moiety

  摘要：

  The discovery that pyrazole-benzyl urea derivatives bearing a 2-molpholinopyrimidine moiety are novel p38 alpha inhibitors is described. A comparative view of the binding modes of SB-203580 and BIRB-796 by structural alignment of two X-ray co-crystal structures was utilized to identify this novel series. Modification of the benzyl group led to compound 2b, a highly potent p38 alpha inhibitor. In in vivo studies, 2b inhibited the production of tumor necrosis factor-alpha in lipopolysaccharide-treated mouse in a dose-dependent manner. Furthermore, the results of a 5-day repeated oral dose toxicity study suggest that 2b has low hepatotoxicity. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.095
• 作为产物：
  描述：

  2,2,2-三氯乙基 3-叔丁基-1-(4-甲基苯基)-1H-吡唑-5-基氨基甲酸酯 、 2-(aminomethyl)-4-fluorophenol 在 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 生成 1-(5-fluoro-2-hydroxybenzyl)-3-(3-t-butyl-1-p-tolyl-1H-pyrazol-5-yl)urea
  参考文献：
  名称：

  Design and synthesis of novel p38α MAP kinase inhibitors: Discovery of pyrazole-benzyl ureas bearing 2-molpholinopyrimidine moiety

  摘要：

  The discovery that pyrazole-benzyl urea derivatives bearing a 2-molpholinopyrimidine moiety are novel p38 alpha inhibitors is described. A comparative view of the binding modes of SB-203580 and BIRB-796 by structural alignment of two X-ray co-crystal structures was utilized to identify this novel series. Modification of the benzyl group led to compound 2b, a highly potent p38 alpha inhibitor. In in vivo studies, 2b inhibited the production of tumor necrosis factor-alpha in lipopolysaccharide-treated mouse in a dose-dependent manner. Furthermore, the results of a 5-day repeated oral dose toxicity study suggest that 2b has low hepatotoxicity. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.095

文献信息

• ARYLMETHYLENE UREA DERIVATIVE AND USE THEREOF
  申请人：Ohno Michihiro

  公开号：US20100016319A1

  公开（公告）日：2010-01-21

  This invention relates to a pharmaceutical comprising as an effective ingredient an arylmethylene urea exemplified by the following formula: or a pharmaceutically acceptable salt thereof. The arylmethylene urea and the pharmaceutically acceptable salts thereof are useful for therapy or prophylaxis of inflammatory bowel disease and overactive bladder.

  本发明涉及一种药物，其有效成分为以下式子所示的芳基亚甲基脲或其药学上可接受的盐： 该芳基亚甲基脲及其药学上可接受的盐可用于治疗或预防炎症性肠病和过度活跃的膀胱。
• EP1970375
  申请人：——

  公开号：——

  公开（公告）日：——