2,2,2-trichloroethyl 5-tert-butyl-3-(5-oxo-1,4-diazepane-1-carbonyl)thiophen-2-ylcarbamate | 1351667-10-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2,2,2-trichloroethyl 5-tert-butyl-3-(5-oxo-1,4-diazepane-1-carbonyl)thiophen-2-ylcarbamate
• CAS: 1351667-10-1
• 化学式: C₁₇H₂₂Cl₃N₃O₄S
• 分子量: 470.804
• InChiKey: ZSCGJQBVRWNQJY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.93
• 重原子数：
  28.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  87.74
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  2,2,2-trichloroethyl 5-tert-butyl-3-(5-oxo-1,4-diazepane-1-carbonyl)thiophen-2-ylcarbamate 、 3,4-二氯苯胺 在 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 为溶剂， 以3.7 mg的产率得到1-(5-tert-butyl-3-(5-oxo-1,4-diazepane-1-carbonyl)thiophen-2-yl)-3-(3,4-dichlorophenyl)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：

  2,3,6,7-四氢-(1H)-1,4-二氮杂卓-5(4H)-酮 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 、 sodium hydroxide 作用下， 以 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 0.5h， 生成 2,2,2-trichloroethyl 5-tert-butyl-3-(5-oxo-1,4-diazepane-1-carbonyl)thiophen-2-ylcarbamate
  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