| 1316736-21-6

• 分子结构分类: 有机化合物 - 有机卤素化合物
• CAS: 1316736-21-6
• 化学式: C₁₀H₁₀BrNO
• 分子量: 244.068
• InChiKey: WEBHXXBBDYMULJ-RHQRLBAQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.97
• 重原子数：
  13.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  43.09
• 氢给体数：
  1.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  在 劳森试剂 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 5.0h， 生成 2-(1-(4-bromophenyl-2,3,5,6-d4)cyclopropyl)-4-(pyridin-4-yl)thiazole
  参考文献：
  名称：

  Examining the Mechanism of Action of a Kinesin Inhibitor Using Stable Isotope Labeled Inhibitors for Cross-Linking (SILIC)

  摘要：

  It is difficult to determine a chemical inhibitor's binding site in multiprotein mixtures, particularly when high-resolution structural studies are not straightforward. Building upon previous research involving photo-cross-linking and the use of mixtures of stable isotopes, we report a method, Stable Isotope Labeled Inhibitors for Cross-linking (SILIC), for mapping a small molecule inhibitor's binding site in its target protein. In SILIC, structure-activity relationship data is used to design inhibitor analogues that incorporate a photo-cross-linking group along with either natural or 'heavy' stable isotopes. An equimolar mixture of these inhibitor analogues is cross-linked to the target protein to yield a robust signature for identifying inhibitor-modified peptide fragments in complex mass spectrometry data. As a proof of concept, we applied this approach to an ATP-competitive inhibitor of kinesin-5, a widely conserved motor protein required for cell division and an anticancer drug target. This analysis, along with mutagenesis studies, suggests that the inhibitor binds at an allosteric site in the motor protein.

  DOI：

  10.1021/ja204561q
• 作为产物：
  描述：

  氘代甲苯 在 硫酸 、 四丁基溴化铵 、 sodium bromide 、 potassium hydroxide 作用下， 以 water-d2 、 二氯甲烷 、 氘代甲苯 、 溶剂黄146 为溶剂， 反应 35.5h， 生成
  参考文献：
  名称：

  Examining the Mechanism of Action of a Kinesin Inhibitor Using Stable Isotope Labeled Inhibitors for Cross-Linking (SILIC)

  摘要：

  It is difficult to determine a chemical inhibitor's binding site in multiprotein mixtures, particularly when high-resolution structural studies are not straightforward. Building upon previous research involving photo-cross-linking and the use of mixtures of stable isotopes, we report a method, Stable Isotope Labeled Inhibitors for Cross-linking (SILIC), for mapping a small molecule inhibitor's binding site in its target protein. In SILIC, structure-activity relationship data is used to design inhibitor analogues that incorporate a photo-cross-linking group along with either natural or 'heavy' stable isotopes. An equimolar mixture of these inhibitor analogues is cross-linked to the target protein to yield a robust signature for identifying inhibitor-modified peptide fragments in complex mass spectrometry data. As a proof of concept, we applied this approach to an ATP-competitive inhibitor of kinesin-5, a widely conserved motor protein required for cell division and an anticancer drug target. This analysis, along with mutagenesis studies, suggests that the inhibitor binds at an allosteric site in the motor protein.

  DOI：

  10.1021/ja204561q