Ethyl 5-[2-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]ethyl]pyrazolo[1,5-a]pyrimidine-3-carboxylate | 1436686-20-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: Ethyl 5-[2-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]ethyl]pyrazolo[1,5-a]pyrimidine-3-carboxylate
• 英文别名: ethyl 5-[2-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]ethyl]pyrazolo[1,5-a]pyrimidine-3-carboxylate
• CAS: 1436686-20-2
• 化学式: C₂₁H₃₀N₄O₄
• 分子量: 402.494
• InChiKey: JTWDQFUJRIMXIJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  86
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Ethyl 5-[2-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]ethyl]pyrazolo[1,5-a]pyrimidine-3-carboxylate 在 甲醇 、 lithium hydroxide 作用下， 以 水 为溶剂， 生成
  参考文献：
  名称：

  Discovery of novel pyrazolo[1,5-a]pyrimidines as potent pan-Pim inhibitors by structure- and property-based drug design

  摘要：

  Pim kinases are promising targets for the development of cancer therapeutics. Among the three Pim isoforms, Pim-2 is particularly important in multiple myeloma, yet is the most difficult to inhibit due to its high affinity for ATP. We identified compound 1 via high throughput screening. Using property-based drug design and co-crystal structures with Pim-1 kinase to guide analog design, we were able to improve potency against all three Pim isoforms including a significant 10,000-fold gain against Pim-2. Compound 17 is a novel lead with low picomolar potency on all three Pim kinase isoforms. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.04.020
• 作为产物：
  描述：

  5-溴吡唑并[1,5-a]嘧啶-3-羧酸乙酯 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 palladium on activated charcoal 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 生成 Ethyl 5-[2-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]ethyl]pyrazolo[1,5-a]pyrimidine-3-carboxylate
  参考文献：
  名称：

  Discovery of novel pyrazolo[1,5-a]pyrimidines as potent pan-Pim inhibitors by structure- and property-based drug design

  摘要：

  Pim kinases are promising targets for the development of cancer therapeutics. Among the three Pim isoforms, Pim-2 is particularly important in multiple myeloma, yet is the most difficult to inhibit due to its high affinity for ATP. We identified compound 1 via high throughput screening. Using property-based drug design and co-crystal structures with Pim-1 kinase to guide analog design, we were able to improve potency against all three Pim isoforms including a significant 10,000-fold gain against Pim-2. Compound 17 is a novel lead with low picomolar potency on all three Pim kinase isoforms. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.04.020