2-(3-(3-tert-butyl-5-(3-naphthalen-1-ylureido)-1H-pyrazol-1-yl)-phenylamino)-N-(2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)ethyl)-acetamide | 1200442-84-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-(3-(3-tert-butyl-5-(3-naphthalen-1-ylureido)-1H-pyrazol-1-yl)-phenylamino)-N-(2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)ethyl)-acetamide
• 英文别名: 2-[3-[3-tert-butyl-5-(naphthalen-1-ylcarbamoylamino)pyrazol-1-yl]anilino]-N-[2-(2,5-dioxopyrrol-1-yl)ethyl]acetamide
• CAS: 1200442-84-7
• 化学式: C₃₂H₃₃N₇O₄
• 分子量: 579.659
• InChiKey: XFHQXMRGPYFKCN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  43
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  138
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-(3-(3-tert-butyl-5-(3-naphthalen-1-ylureido)-1H-pyrazol-1-yl)-phenylamino)acetic acid 、 N-(2-氨基乙基)马来酰亚胺三氟乙酸盐 在 N-甲基吗啉 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以1 mg的产率得到2-(3-(3-tert-butyl-5-(3-naphthalen-1-ylureido)-1H-pyrazol-1-yl)-phenylamino)-N-(2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)ethyl)-acetamide
  参考文献：
  名称：

  Displacement Assay for the Detection of Stabilizers of Inactive Kinase Conformations

  摘要：

  Targeting protein kinases with small molecules outside the highly conserved ATP pocket to stabilize inactive kinase conformati oils is becoming a more desirable approach in kinase inhibitor research, since these molecules have advanced pharmacological properties compared to compounds exclusively targeting the ATP pocket. Traditional screening approaches for kinase inhibitors arc often based on enzyme activity, but they may miss inhibitors that stabilize inactive kinase conformations by enriching the active state of the kinase. Here we present the development of a kinase binding assay employing a pyraZOIOUrea type III inhibitor and enzyme fragment complementation (EFQ technology that is suitable to screen stabilizers ofenzyniatically inactive kinases. To validate this assay system, we report tile binding characteristics of a series of kinase inhibitors to inactive p38(x and JNK2. Additionally, we present protein X-ray crystallography studies to examine the binding modes of potent quinolinc-based DFG-out binders in p38a.

  DOI：

  10.1021/jm901297e

文献信息

• Displacement Assay for the Detection of Stabilizers of Inactive Kinase Conformations
  作者：Sabine Klüter、Christian Grütter、Tabassum Naqvi、Matthias Rabiller、Jeffrey R. Simard、Vijaykumar Pawar、Matthäus Getlik、Daniel Rauh

  DOI：10.1021/jm901297e

  日期：2010.1.14

  Targeting protein kinases with small molecules outside the highly conserved ATP pocket to stabilize inactive kinase conformati oils is becoming a more desirable approach in kinase inhibitor research, since these molecules have advanced pharmacological properties compared to compounds exclusively targeting the ATP pocket. Traditional screening approaches for kinase inhibitors arc often based on enzyme activity, but they may miss inhibitors that stabilize inactive kinase conformations by enriching the active state of the kinase. Here we present the development of a kinase binding assay employing a pyraZOIOUrea type III inhibitor and enzyme fragment complementation (EFQ technology that is suitable to screen stabilizers ofenzyniatically inactive kinases. To validate this assay system, we report tile binding characteristics of a series of kinase inhibitors to inactive p38(x and JNK2. Additionally, we present protein X-ray crystallography studies to examine the binding modes of potent quinolinc-based DFG-out binders in p38a.