N(1)-(6-chloropyrazin-2-yl)propane-1,3-diamine | 1138220-49-1

• 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: N(1)-(6-chloropyrazin-2-yl)propane-1,3-diamine
• 英文别名: N'-(6-chloropyrazin-2-yl)propane-1,3-diamine
• CAS: 1138220-49-1
• 化学式: C₇H₁₁ClN₄
• 分子量: 186.644
• InChiKey: FXUIUHBEYQCAPH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  63.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-3-(3-BORONOPHENYL)ACRYLICACID锛圵S203778锛,WUXIAPPTEC" 、 N(1)-(6-chloropyrazin-2-yl)propane-1,3-diamine 、 三氟乙酸 在 bis-triphenylphosphine-palladium(II) chloride 、 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 水 、 乙腈 为溶剂， 生成 (E)-3-{3-[6-(3-aminopropylamino)pyrazin-2-yl]phenyl}acrylic acid trifluoroacetate
  参考文献：
  名称：

  Hit to Lead Account of the Discovery of a New Class of Inhibitors of Pim Kinases and Crystallographic Studies Revealing an Unusual Kinase Binding Mode

  摘要：

  A series of inhibitors of Pim-2 kinase identified by high-throughput screening is described. Details of the hit validation and lead generation process and structure-activity relationship (SAR) studies are presented. Disclosure of an unconventional binding mode for 1, as revealed by X-ray crystallography using the highly homologous Pim-1 protein, is also presented, and observed binding features are shown to correlate with the Pim-2 SAR. While highly selective within the kinase family, the series shows similar potency for both Pim-1 and Pim-2, which was expected on the basis of homology, but unusual in light of reports in the literature documenting a bias for Pim-1. A rationale for these observations based on Pim-1 and Pim-2 K(M(ATP)) values is suggested. Some interesting cross reactivity with casein kinase-2 was also identified, and structural features which may contribute to the association are discussed.

  DOI：

  10.1021/jm801242y
• 作为产物：
  描述：

  2,6-二氯吡嗪 、 1,3-丙二胺 以 二氯甲烷 为溶剂， 生成 N(1)-(6-chloropyrazin-2-yl)propane-1,3-diamine
  参考文献：
  名称：

  Hit to Lead Account of the Discovery of a New Class of Inhibitors of Pim Kinases and Crystallographic Studies Revealing an Unusual Kinase Binding Mode

  摘要：

  A series of inhibitors of Pim-2 kinase identified by high-throughput screening is described. Details of the hit validation and lead generation process and structure-activity relationship (SAR) studies are presented. Disclosure of an unconventional binding mode for 1, as revealed by X-ray crystallography using the highly homologous Pim-1 protein, is also presented, and observed binding features are shown to correlate with the Pim-2 SAR. While highly selective within the kinase family, the series shows similar potency for both Pim-1 and Pim-2, which was expected on the basis of homology, but unusual in light of reports in the literature documenting a bias for Pim-1. A rationale for these observations based on Pim-1 and Pim-2 K(M(ATP)) values is suggested. Some interesting cross reactivity with casein kinase-2 was also identified, and structural features which may contribute to the association are discussed.

  DOI：

  10.1021/jm801242y