3-[(2R)-1-(dimethylamino)propan-2-yl]oxy-5-[[4-(methylamino)pyridin-2-yl]amino]pyrazine-2-carbonitrile | 1404095-19-7

• 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-[(2R)-1-(dimethylamino)propan-2-yl]oxy-5-[[4-(methylamino)pyridin-2-yl]amino]pyrazine-2-carbonitrile
• CAS: 1404095-19-7
• 化学式: C₁₆H₂₁N₇O
• 分子量: 327.389
• InChiKey: SIMIJFXHWJHJLE-LLVKDONJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  99
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  R-(-)-1-二甲氨基-2-丙醇 在 tris-(dibenzylideneacetone)dipalladium(0) 、 sodium hydride 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 1,4-二氧六环 、 mineral oil 为溶剂， 反应 15.5h， 生成 3-[(2R)-1-(dimethylamino)propan-2-yl]oxy-5-[[4-(methylamino)pyridin-2-yl]amino]pyrazine-2-carbonitrile
  参考文献：
  名称：

  Discovery of 3-Alkoxyamino-5-(pyridin-2-ylamino)pyrazine-2-carbonitriles as Selective, Orally Bioavailable CHK1 Inhibitors

  摘要：

  Inhibitors of checkpoint kinase 1 (CHK1) are of current interest as potential antitumor agents, but the most advanced inhibitor series reported to date are not orally bioavailable. A novel series of potent and orally bioavailable 3-alkoxyamino-5-(pyridin-2-ylamino)pyrazine-2-carbonitrile CHK1 inhibitors was generated by hybridization of two lead scaffolds derived from fragment based drug design and optimized for CHK1 potency and high selectivity using a cell based assay cascade. Efficient in vivo pharmacokinetic assessment was used to identify compounds with prolonged exposure following oral dosing. The optimized compound (CCT244747) was a potent and highly selective CHK1 inhibitor, which modulated the DNA damage response pathway in human tumor xenografts and showed antitumor activity in combination with genotoxic chemotherapies and as a single agent

  DOI：

  10.1021/jm3012933