3-(6-(1,4-diazepan-1-yl)pyridin-2-yl)-6-(6-methylpyrazin-2-yl)imidazo[1,5-a]pyrazine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并[1,5-a]吡嗪
• 英文名称: 3-(6-(1,4-diazepan-1-yl)pyridin-2-yl)-6-(6-methylpyrazin-2-yl)imidazo[1,5-a]pyrazine
• 英文别名: 3-[6-(1,4-Diazepan-1-yl)pyridin-2-yl]-6-(6-methylpyrazin-2-yl)imidazo[1,5-a]pyrazine；3-[6-(1,4-diazepan-1-yl)pyridin-2-yl]-6-(6-methylpyrazin-2-yl)imidazo[1,5-a]pyrazine
• 化学式: C₂₁H₂₂N₈
• 分子量: 386.459
• InChiKey: NIRPQZMBABINPZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  84.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  6-氯吡啶-2-羧酸 在 盐酸 、 potassium fluoride 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 甲醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 149.5h， 生成 3-(6-(1,4-diazepan-1-yl)pyridin-2-yl)-6-(6-methylpyrazin-2-yl)imidazo[1,5-a]pyrazine
  参考文献：
  名称：

  Discovery of 5-Azaindazole (GNE-955) as a Potent Pan-Pim Inhibitor with Optimized Bioavailability

  摘要：

  Pim kinases have been identified as promising therapeutic targets for hematologic-oncology indications, including multiple myeloma and certain leukemia. Here, we describe our continued efforts in optimizing a lead series by improving bioavailability while maintaining high inhibitory potency against all three Pim kinase isoforms. The discovery of extensive intestinal metabolism and major metabolites helped refine our design strategy, and we observed that optimizing the pharmacokinetic properties first and potency second was a more successful approach than the reverse. In the resulting work, novel analogs such as 20 (GNE-955) were discovered bearing 5-azaindazole core with noncanonical hydrogen bonding to the hinge.

  DOI：

  10.1021/acs.jmedchem.7b00418