6-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-1-yl)-N-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)hexanamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 6-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-1-yl)-N-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)hexanamide
• 英文别名: 6-[4-[6-[(6-acetyl-8-cyclopentyl-5-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl)amino]pyridin-3-yl]piperazin-1-yl]-N-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]hexanamide
• 化学式: C₄₃H₄₈N₁₀O₇
• 分子量: 816.917
• InChiKey: HJEZCPKGRBNZSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  60
• 可旋转键数：
  13
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  207
• 氢给体数：
  3
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  泊马度胺 在 草酰氯 、 N,N-二异丙基乙胺 、 sodium iodide 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 丙酮 为溶剂， 反应 40.0h， 生成 6-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-1-yl)-N-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)hexanamide
  参考文献：
  名称：

  Selective degradation of CDK6 by a palbociclib based PROTAC

  摘要：

  Development of selective kinase inhibitors that target the ATP binding site continues to be a challenge largely due to similar binding pockets. Palbociclib is a cyclin-dependent kinase inhibitor that targets the ATP binding site of CDK4 and CDK6 with similar potency. The enzymatic function associated with the kinase can be effectively probed using kinase inhibitors however the kinase-independent functions cannot. Herein, we report a palbociclib based PROTAC that selectively degrades CDK6 while sparing the homolog CDK4. We used competition studies to characterize the binding and mechanism of CDK6 degradation.

  DOI：

  10.1016/j.bmcl.2019.03.035

文献信息

• Selective degradation of CDK6 by a palbociclib based PROTAC
  作者：Sandeep Rana、Mourad Bendjennat、Smit Kour、Hannah M. King、Smitha Kizhake、Muhammad Zahid、Amarnath Natarajan

  DOI：10.1016/j.bmcl.2019.03.035

  日期：2019.6

  Development of selective kinase inhibitors that target the ATP binding site continues to be a challenge largely due to similar binding pockets. Palbociclib is a cyclin-dependent kinase inhibitor that targets the ATP binding site of CDK4 and CDK6 with similar potency. The enzymatic function associated with the kinase can be effectively probed using kinase inhibitors however the kinase-independent functions cannot. Herein, we report a palbociclib based PROTAC that selectively degrades CDK6 while sparing the homolog CDK4. We used competition studies to characterize the binding and mechanism of CDK6 degradation.