1-(3-tert-butyl-1H-pyrazol-5-yl)-3-(naphthalen-2-yl)urea | 1351667-18-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1-(3-tert-butyl-1H-pyrazol-5-yl)-3-(naphthalen-2-yl)urea
• CAS: 1351667-18-9
• 化学式: C₁₈H₂₀N₄O
• 分子量: 308.383
• InChiKey: IALGGMLRCPXURQ-UHFFFAOYSA-N

物化性质

• 沸点：
  437.6±33.0 °C(Predicted)
• 密度：
  1.273±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  23.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  69.81
• 氢给体数：
  3.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  硫代吗啉-4-甲酰氯-1,1-二氧化物 、 1-(3-tert-butyl-1H-pyrazol-5-yl)-3-(naphthalen-2-yl)urea 在 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 15.0h， 以108.2 mg的产率得到1-(5-tert-butyl-2-(1,1-dioxothiomorpholine-4-carbonyl)-2H-pyrazol-3 yl)-3-naphthalen-2-ylurea
  参考文献：
  名称：

  Discovery of a novel class of non-ATP site DFG-out state p38 inhibitors utilizing computationally assisted virtual fragment-based drug design (vFBDD)

  摘要：

  Discovery of a new class of DFG-out p38α kinase inhibitors with no hinge interaction is described. A computationally assisted, virtual fragment-based drug design (vFBDD) platform was utilized to identify novel non-aromatic fragments which make productive hydrogen bond interactions with Arg 70 on the αC-helix. Molecules incorporating these fragments were found to be potent inhibitors of p38 kinase. X-ray co-crystal structures confirmed the predicted binding modes. A lead compound was identified as a potent (p38α IC(50)=22 nM) and highly selective (≥ 150-fold against 150 kinase panel) DFG-out p38 kinase inhibitor.

  DOI：

  10.1016/j.bmcl.2011.09.078
• 作为产物：
  描述：

  3-叔丁基-吡唑-5-胺 、 2-萘基异氰酸酯 以 甲苯 为溶剂， 反应 26.0h， 以50%的产率得到1-(3-tert-butyl-1H-pyrazol-5-yl)-3-(naphthalen-2-yl)urea
  参考文献：
  名称：

  Discovery of a novel class of non-ATP site DFG-out state p38 inhibitors utilizing computationally assisted virtual fragment-based drug design (vFBDD)

  摘要：

  Discovery of a new class of DFG-out p38α kinase inhibitors with no hinge interaction is described. A computationally assisted, virtual fragment-based drug design (vFBDD) platform was utilized to identify novel non-aromatic fragments which make productive hydrogen bond interactions with Arg 70 on the αC-helix. Molecules incorporating these fragments were found to be potent inhibitors of p38 kinase. X-ray co-crystal structures confirmed the predicted binding modes. A lead compound was identified as a potent (p38α IC(50)=22 nM) and highly selective (≥ 150-fold against 150 kinase panel) DFG-out p38 kinase inhibitor.

  DOI：

  10.1016/j.bmcl.2011.09.078