3-(6-(methyl(4-(trifluoromethoxy)phenyl)amino)-pyrimidin-4-yl)benzamide | 959575-91-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 3-(6-(methyl(4-(trifluoromethoxy)phenyl)amino)-pyrimidin-4-yl)benzamide
• 英文别名: 3-{6-[Methyl-(4-trifluoromethoxy-phenyl)-amino]-pyrimidin-4-yl}-benzamide；3-[6-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-4-yl]benzamide
• CAS: 959575-91-8
• 化学式: C₁₉H₁₅F₃N₄O₂
• 分子量: 388.349
• InChiKey: XREUCZRFKWBEGJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  81.3
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  对三氟甲氧基苯胺 在 四(三苯基膦)钯 、 sodium hydride 、 sodium carbonate 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 13.33h， 生成 3-(6-(methyl(4-(trifluoromethoxy)phenyl)amino)-pyrimidin-4-yl)benzamide
  参考文献：
  名称：

  Direct Binding Assay for the Detection of Type IV Allosteric Inhibitors of Abl

  摘要：

  Abelson (Abl) tyrosine kinase is an important cellular enzyme that is rendered constitutively active in the breakpoint cluster region (BCR)-Abl fusion protein, contributing to several forms of leukemia. Although inhibiting BCR-Abl activity with imatinib shows great clinical success, many patients acquire secondary mutations that result in resistance to imatinib. Second-generation inhibitors such as dasatinib and nilotinib can overcome the majority of these mutations but fail to treat patients with an especially prevalent T315I mutation at the gatekeeper position of the kinase domain. However, a combination of nilotinib with an allosteric type IV inhibitor was recently shown to overcome this clinically relevant point mutation. In this study, we present the development of a direct binding assay that enables the straightforward detection of allosteric inhibitors which bind within the myristate pocket of Abl. The assay is amenable to high-throughput screening and exclusively detects the binding of ligands to this unique allosteric site.

  DOI：

  10.1021/ja303858w

文献信息

• Direct Binding Assay for the Detection of Type IV Allosteric Inhibitors of Abl
  作者：Ralf Schneider、Christian Becker、Jeffrey R. Simard、Matthäus Getlik、Nina Bohlke、Petra Janning、Daniel Rauh

  DOI：10.1021/ja303858w

  日期：2012.6.6

  Abelson (Abl) tyrosine kinase is an important cellular enzyme that is rendered constitutively active in the breakpoint cluster region (BCR)-Abl fusion protein, contributing to several forms of leukemia. Although inhibiting BCR-Abl activity with imatinib shows great clinical success, many patients acquire secondary mutations that result in resistance to imatinib. Second-generation inhibitors such as dasatinib and nilotinib can overcome the majority of these mutations but fail to treat patients with an especially prevalent T315I mutation at the gatekeeper position of the kinase domain. However, a combination of nilotinib with an allosteric type IV inhibitor was recently shown to overcome this clinically relevant point mutation. In this study, we present the development of a direct binding assay that enables the straightforward detection of allosteric inhibitors which bind within the myristate pocket of Abl. The assay is amenable to high-throughput screening and exclusively detects the binding of ligands to this unique allosteric site.