5-(4-cyanobenzyl)-7-hydroxy-N-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide | 1436685-44-7

• 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: 5-(4-cyanobenzyl)-7-hydroxy-N-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide
• CAS: 1436685-44-7
• 化学式: C₂₂H₁₅N₇O₂
• 分子量: 409.407
• InChiKey: DITFQVUGUFEPMW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.03
• 重原子数：
  31.0
• 可旋转键数：
  4.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  131.99
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  在 水 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 lithium hydroxide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 5-(4-cyanobenzyl)-7-hydroxy-N-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide
  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

文献信息

• Discovery of novel pyrazolo[1,5-a]pyrimidines as potent pan-Pim inhibitors by structure- and property-based drug design
  作者：Xiaojing Wang、Steven Magnuson、Rich Pastor、Eric Fan、Huiyong Hu、Vickie Tsui、Wei Deng、Jeremy Murray、Micah Steffek、Heidi Wallweber、John Moffat、Jason Drummond、Grace Chan、Eric Harstad、Allen J. Ebens

  DOI：10.1016/j.bmcl.2013.04.020

  日期：2013.6

  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.