C-[1-(6-chloropyrazin-2-yl)piperidin-4-yl]methylamine | 1138220-57-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: C-[1-(6-chloropyrazin-2-yl)piperidin-4-yl]methylamine
• 英文别名: [1-(6-Chloropyrazin-2-yl)piperidin-4-yl]methanamine；[1-(6-chloropyrazin-2-yl)piperidin-4-yl]methanamine
• CAS: 1138220-57-1
• 化学式: C₁₀H₁₅ClN₄
• 分子量: 226.709
• InChiKey: KUGQKALCHFAGPN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  55
• 氢给体数：
  1
• 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" 、 C-[1-(6-chloropyrazin-2-yl)piperidin-4-yl]methylamine 在 bis-triphenylphosphine-palladium(II) chloride 、 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (E)-3-(3-{6-[4-(aminomethyl)piperidin-1-yl]pyrazin-2-yl}phenyl)acrylic acid
  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 、 4-氨甲基哌啶 以 二氯甲烷 为溶剂， 生成 C-[1-(6-chloropyrazin-2-yl)piperidin-4-yl]methylamine
  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

文献信息

• 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
  作者：Kevin Qian、Lian Wang、Charles L. Cywin、Bennett T. Farmer、Eugene Hickey、Carol Homon、Scott Jakes、Mohammed A. Kashem、George Lee、Scott Leonard、Jun Li、Ronald Magboo、Wang Mao、Edward Pack、Charlene Peng、Anthony Prokopowicz、Morgan Welzel、John Wolak、Tina Morwick

  DOI：10.1021/jm801242y

  日期：2009.4.9

  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.