tert-butyl 3-(2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)azetidine-1-carboxylate | 1394076-98-2

• 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: tert-butyl 3-(2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)azetidine-1-carboxylate
• 英文别名: Tert-butyl 3-(2-chloro-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl)azetidine-1-carboxylate
• CAS: 1394076-98-2
• 化学式: C₁₈H₂₃ClN₄O₃S
• 分子量: 410.925
• InChiKey: QTRXMRSZDDTHFS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  96
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-(2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)azetidine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以70%的产率得到4-(6-(azetidin-3-yl)-2-chlorothieno[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
• 作为产物：
  描述：

  4-(2-chloro-6-iodothieno[3,2-d]pyrimidin-4-yl)morpholine 、 1-Boc-3-碘氮杂环丁烷 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 作用下， 反应 1.0h， 以1.1 g的产率得到tert-butyl 3-(2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)azetidine-1-carboxylate
  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

文献信息

• The Design and Identification of Brain Penetrant Inhibitors of Phosphoinositide 3-Kinase α
  作者：Timothy P. Heffron、Laurent Salphati、Bruno Alicke、Jonathan Cheong、Jennafer Dotson、Kyle Edgar、Richard Goldsmith、Stephen E. Gould、Leslie B. Lee、John D. Lesnick、Cristina Lewis、Chudi Ndubaku、Jim Nonomiya、Alan G. Olivero、Jodie Pang、Emile G. Plise、Steve Sideris、Sean Trapp、Jeffrey Wallin、Lan Wang、Xiaolin Zhang

  DOI：10.1021/jm300867c

  日期：2012.9.27

  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.