5-tert-butyl-2-(3-(4-cyanonaphthalen-1-yl)ureido)thiophene-3-carboxylic acid | 1351667-01-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 5-tert-butyl-2-(3-(4-cyanonaphthalen-1-yl)ureido)thiophene-3-carboxylic acid
• CAS: 1351667-01-0
• 化学式: C₂₁H₁₉N₃O₃S
• 分子量: 393.466
• InChiKey: NLTUBINKXFANRW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.41
• 重原子数：
  28.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  102.22
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2,3,6,7-四氢-(1H)-1,4-二氮杂卓-5(4H)-酮 、 5-tert-butyl-2-(3-(4-cyanonaphthalen-1-yl)ureido)thiophene-3-carboxylic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 27.0h， 以6.8 mg的产率得到1-(5-tert-butyl-3-(5-oxo-1,4-diazepane-1-carbonyl)thiophen-2-yl)-3-(4-cyanonaphthalen-1-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
• 作为产物：
  描述：

  4-氨基-1-萘羧腈 在 盐酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲苯 为溶剂， 反应 25.5h， 生成 5-tert-butyl-2-(3-(4-cyanonaphthalen-1-yl)ureido)thiophene-3-carboxylic acid
  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