N-(3-tert-butyl-1-phenyl-1H-pyrazol-5-yl)-N'-(4-fluorophenyl)urea

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-(3-tert-butyl-1-phenyl-1H-pyrazol-5-yl)-N'-(4-fluorophenyl)urea
• 英文别名: 1-(5-Tert-butyl-2-phenylpyrazol-3-yl)-3-(4-fluorophenyl)urea；1-(5-tert-butyl-2-phenylpyrazol-3-yl)-3-(4-fluorophenyl)urea
• 化学式: C₂₀H₂₁FN₄O
• 分子量: 352.411
• InChiKey: AZHMHNJNZKTQCM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  59
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  异氰酸对氟苯基酯 、 3-叔丁基-1-苯基-1H-吡唑-5-胺 以 二氯甲烷 为溶剂， 反应 0.33h， 以86%的产率得到N-(3-tert-butyl-1-phenyl-1H-pyrazol-5-yl)-N'-(4-fluorophenyl)urea
  参考文献：
  名称：

  Selective targeting of the αC and DFG-out pocket in p38 MAPK

  摘要：

  The p38 MAPK cascade is a key signaling pathway linked to a multitude of physiological functions and of central importance in inflammatory and autoimmune diseases. Although studied extensively, little is known about how conformation-specific inhibitors alter signaling outcomes. Here, we have explored the highly dynamic back pocket of p38 MAPK with allosteric urea fragments. However, screening against known off-targets showed that these fragments maintained the selectivity issues of their parent compound BIRB-796, while combination with the hinge-binding motif of VPC-00628 greatly enhanced inhibitor selectivity. Further efforts focused therefore on the exploration of the αC-out pocket of p38 MAPK, yielding compound 137 as a highly selective type-II inhibitor. Even though 137 is structurally related to a recent p38 type-II chemical probe, SR-318, the data presented here provide valuable insights into back-pocket interactions that are not addressed in SR-318 and it provides an alternative chemical tool with good cellular activity targeting also the p38 back pocket.

  DOI：

  10.1016/j.ejmech.2020.112721