4-(2-chloro-6-(3-(2-methoxyethoxy)oxetan-3-yl)thieno[3,2-d]pyrimidin-4-yl)morpholine | 1394077-01-0

• 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: 4-(2-chloro-6-(3-(2-methoxyethoxy)oxetan-3-yl)thieno[3,2-d]pyrimidin-4-yl)morpholine
• 英文别名: 4-[2-Chloro-6-[3-(2-methoxyethoxy)oxetan-3-yl]thieno[3,2-d]pyrimidin-4-yl]morpholine
• CAS: 1394077-01-0
• 化学式: C₁₆H₂₀ClN₃O₄S
• 分子量: 385.871
• InChiKey: JZSWKTMLYULOEP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  94.2
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-氨基嘧啶-5-硼酸频哪酯 、 4-(2-chloro-6-(3-(2-methoxyethoxy)oxetan-3-yl)thieno[3,2-d]pyrimidin-4-yl)morpholine 在 二氯双[二叔丁基-(4-二甲基氨基苯基)膦]钯(II) 、 potassium acetate 作用下， 以 水 、 乙腈 为溶剂， 反应 0.5h， 以30%的产率得到5-(6-(3-(2-Methoxyethoxy)oxetan-3-yl)-4-morpholinothieno[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine
  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：

  2-氯-4-(4-吗啉基)噻吩并[3,2-D]嘧啶 在 正丁基锂 、 sodium hydride 作用下， 以 四氢呋喃 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.67h， 生成 4-(2-chloro-6-(3-(2-methoxyethoxy)oxetan-3-yl)thieno[3,2-d]pyrimidin-4-yl)morpholine
  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