rac-2-(2-hydroxy-1,1-dimethylethyl)-5-methyl-1,2,4,10-tetrahydro-3-oxa-10-azaphenanthren-9-one | 1520888-47-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: rac-2-(2-hydroxy-1,1-dimethylethyl)-5-methyl-1,2,4,10-tetrahydro-3-oxa-10-azaphenanthren-9-one
• 英文别名: 2-(2-hydroxy-1,1-dimethylethyl)-5-methyl-1,2,4,10-tetrahydro-3-oxa-10-azaphenanthren-9-one；3-(2-hydroxy-1,1-dimethylethyl)-10-methyl-1,3,4,5-tetrahydropyrano[43-c]isoquinolin-6-one；2-(2-Hydroxy-1,1-dimethyl-ethyl)-5-methyl-1,2,4,10-tetrahydro-3-oxa-10-aza-phenanthren-9-one；3-(1-hydroxy-2-methylpropan-2-yl)-10-methyl-1,3,4,5-tetrahydropyrano[4,3-c]isoquinolin-6-one
• CAS: 1520888-47-4
• 化学式: C₁₇H₂₁NO₃
• 分子量: 287.359
• InChiKey: JZXQZQOGBFSTTQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  rac-2-(2-hydroxy-1,1-dimethylethyl)-5-methyl-1,2,4,10-tetrahydro-3-oxa-10-azaphenanthren-9-one 在 OD column 作用下， 以14.4 mg的产率得到(3S)-3-(2-hydroxy-1,1-dimethylethyl)-10-methyl-1,3,4,5-tetrahydropyrano[4,3-c]isoquinolin-6-one
  参考文献：
  名称：

  [EN] PYRANOPYRIDONE INHIBITORS OF TANKYRASE
  [FR] INHIBITEURS PYRANOPYRIDONE DE LA TANKYRASE

  摘要：

  提供的化合物具有以下公式或其药学上可接受的盐，其中X、M、Y、R1和R2的定义如本文所述。这些化合物具有抗癌活性。

  公开号：

  WO2013189904A1
• 作为产物：
  描述：

  3-(苄氧基)-2,2-二甲基-1-丙醇 在 盐酸 、 tris-(dibenzylideneacetone)dipalladium(0) 、 10 wt% Pd(OH)2 on carbon 、 氨 、 氢气 、 silica gel 、 caesium carbonate 、 pyridinium chlorochromate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 为溶剂， 140.0 ℃ 、300.01 kPa 条件下， 反应 44.5h， 生成 rac-2-(2-hydroxy-1,1-dimethylethyl)-5-methyl-1,2,4,10-tetrahydro-3-oxa-10-azaphenanthren-9-one
  参考文献：
  名称：

  Fragment-Based Drug Design of Novel Pyranopyridones as Cell Active and Orally Bioavailable Tankyrase Inhibitors

  摘要：

  Tankyrase activity has been linked to the regulation of intracellular axin levels, which have been shown to be crucial for the Wnt pathway. Deregulated Wnt signaling is important for the genesis of many diseases including cancer. We describe herein the discovery and development of a new series of tankyrase inhibitors. These pyranopyridones are highly active in various cell-based assays. A fragment/structure based optimization strategy led to a compound with good pharmacokinetic properties that is suitable for in vivo studies and further development.

  DOI：

  10.1021/acsmedchemlett.5b00251

文献信息

• PYRANOPYRIDONE INHIBITORS OF TANKYRASE
  申请人：Hoffmann-La Roche, Inc.

  公开号：US20140121231A1

  公开（公告）日：2014-05-01

  There are provided compounds of the formula or a pharmaceutically acceptable salt thereof wherein X, M, Y, R 1 and R 2 are as defined herein. The compounds have activity as anticancer agents.

  提供以下化合物的公式或其药学上可接受的盐，其中X，M，Y，R1和R2的定义如下。这些化合物具有抗癌活性。
• [EN] PYRANOPYRIDONE INHIBITORS OF TANKYRASE<br/>[FR] INHIBITEURS PYRANOPYRIDONE DE LA TANKYRASE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2013189904A1

  公开（公告）日：2013-12-27

  There are provided compounds of the formula or a pharmaceutically acceptable salt thereof wherein X, M, Y, R1 and R2 are as defined herein. The compounds have activity as anticancer agents.

  提供的化合物具有以下公式或其药学上可接受的盐，其中X、M、Y、R1和R2的定义如本文所述。这些化合物具有抗癌活性。
• Fragment-Based Drug Design of Novel Pyranopyridones as Cell Active and Orally Bioavailable Tankyrase Inhibitors
  作者：Javier de Vicente、Parcharee Tivitmahaisoon、Pamela Berry、David R. Bolin、Daisy Carvajal、Wei He、Kuo-Sen Huang、Cheryl Janson、Lena Liang、Christine Lukacs、Ann Petersen、Hong Qian、Lin Yi、Yong Zhuang、Johannes C. Hermann

  DOI：10.1021/acsmedchemlett.5b00251

  日期：2015.9.10

  Tankyrase activity has been linked to the regulation of intracellular axin levels, which have been shown to be crucial for the Wnt pathway. Deregulated Wnt signaling is important for the genesis of many diseases including cancer. We describe herein the discovery and development of a new series of tankyrase inhibitors. These pyranopyridones are highly active in various cell-based assays. A fragment/structure based optimization strategy led to a compound with good pharmacokinetic properties that is suitable for in vivo studies and further development.