4-(2-(2-(2-(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)ethoxy)ethoxy)ethoxy)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione

• 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: 4-(2-(2-(2-(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)ethoxy)ethoxy)ethoxy)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione
• 英文别名: 4-[2-[2-[2-[4-[6-[(6-Acetyl-8-cyclopentyl-5-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl)amino]pyridin-3-yl]piperazin-1-yl]ethoxy]ethoxy]ethoxy]-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione；4-[2-[2-[2-[4-[6-[(6-acetyl-8-cyclopentyl-5-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl)amino]pyridin-3-yl]piperazin-1-yl]ethoxy]ethoxy]ethoxy]-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione
• 化学式: C₄₃H₄₉N₉O₉
• 分子量: 835.917
• InChiKey: SFFDQTCEQLEBDF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  61
• 可旋转键数：
  16
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  206
• 氢给体数：
  2
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  三甘醇单苄醚 在 偶氮二甲酸二异丙酯 、 palladium 10% on activated carbon 、 氢气 、 三乙酰氧基硼氢化钠 、 戴斯-马丁氧化剂 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 5.0h， 生成 4-(2-(2-(2-(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)ethoxy)ethoxy)ethoxy)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione
  参考文献：
  名称：

  COMPOUND FOR INHIBITING AND DEGRADING CDK

  摘要：

  本发明提供了一种抑制和降解CDK的化合物。具体地，本发明提供了一种由公式I表示的化合物，其基团的定义在说明书中描述。本发明中的化合物具有非常好的抑制细胞周期蛋白依赖性激酶（CDK）的活性，并可用于制备用于治疗与CDK活性相关的疾病的药物。

  公开号：

  US20200216450A1

文献信息

• Substituted glutarimides as CDK inhibitors
  申请人：SHANGHAI MEIZER PHARMACEUTICALS CO., LTD.

  公开号：US11236090B2

  公开（公告）日：2022-02-01

  A compound for inhibiting and degrading cyclin-dependent kinase (CDK) is disclosed. The compound is a substituted glutarimide represented by formula I. The compound can be used in the preparation of drugs for treating diseases related to the activity of the CDK.

  本发明公开了一种用于抑制和降解细胞周期蛋白依赖性激酶（CDK）的化合物。该化合物是由式 I 代表的取代戊二酰亚胺。该化合物可用于制备治疗与 CDK 活性有关的疾病的药物。
• 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.
• COMPOUND FOR INHIBITING AND DEGRADING CDK
  申请人：SHANGHAI MEIZER PHARMACEUTICALS CO., LTD.

  公开号：US20200216450A1

  公开（公告）日：2020-07-09

  The present invention provides is a compound for inhibiting and degrading CDK. Specifically the present invention provides a compound represented by formula I, definitions of radical groups being described in the specification. The compound in the present invention has a very good inhibitory activity for the cyclin-dependent kinase (CDK), and can be used in the preparation of drugs for treating diseases related to the activity of the CDK.

  本发明提供了一种抑制和降解CDK的化合物。具体地，本发明提供了一种由公式I表示的化合物，其基团的定义在说明书中描述。本发明中的化合物具有非常好的抑制细胞周期蛋白依赖性激酶（CDK）的活性，并可用于制备用于治疗与CDK活性相关的疾病的药物。