1-(3-(2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)azetidin-1-yl)ethanone | 1417732-64-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: 1-(3-(2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)azetidin-1-yl)ethanone
• 英文别名: 1-[3-(2-Chloro-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl)azetidin-1-yl]ethanone
• CAS: 1417732-64-9
• 化学式: C₁₅H₁₇ClN₄O₂S
• 分子量: 352.845
• InChiKey: YPCCZFYSUSTZQT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  86.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-氨基嘧啶-5-硼酸频哪酯 、 1-(3-(2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)azetidin-1-yl)ethanone 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 caesium carbonate 作用下， 以 水 为溶剂， 反应 0.33h， 以48%的产率得到1-(3-(2-(2-aminopyrimidin-5-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)azetidin-1-yl)ethanone
  参考文献：
  名称：

  The Design and Identification of Brain Penetrant Inhibitors of Phosphoinositide 3-Kinase α

  摘要：

  Inhibition of phosphoinositide 3-kinase (PI3K) signaling through PI3K alpha has received significant attention for its potential in cancer therapy. While the PI3K pathway is a well-established and widely pursued target for the treatment of many cancer types due to the high frequency of abnormal PI3K signaling, glioblastoma multiforme (GBM) is particularly relevant because the pathway is implicated in more than 80% of GBM cases. Herein, we report the identification of PI3K inhibitors designed to cross the blood-brain barrier (BBB) to engage their target where GBM tumors reside. We leveraged our historical experience with PI3K inhibitors to identify correlations between physicochemical properties and transporter efflux as well as metabolic stability to focus the selection of molecules for further study.

  DOI：

  10.1021/jm300867c
• 作为产物：
  描述：

  4-(2-chloro-6-iodothieno[3,2-d]pyrimidin-4-yl)morpholine 在 copper(l) iodide 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 1-(3-(2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)azetidin-1-yl)ethanone
  参考文献：
  名称：

  The Design and Identification of Brain Penetrant Inhibitors of Phosphoinositide 3-Kinase α

  摘要：

  Inhibition of phosphoinositide 3-kinase (PI3K) signaling through PI3K alpha has received significant attention for its potential in cancer therapy. While the PI3K pathway is a well-established and widely pursued target for the treatment of many cancer types due to the high frequency of abnormal PI3K signaling, glioblastoma multiforme (GBM) is particularly relevant because the pathway is implicated in more than 80% of GBM cases. Herein, we report the identification of PI3K inhibitors designed to cross the blood-brain barrier (BBB) to engage their target where GBM tumors reside. We leveraged our historical experience with PI3K inhibitors to identify correlations between physicochemical properties and transporter efflux as well as metabolic stability to focus the selection of molecules for further study.

  DOI：

  10.1021/jm300867c