5-[6-(3-甲氧基-3-氧杂环丁基)-7-甲基-4-(4-吗啉基)噻吩并[3,2-d]嘧啶-2-基]-2-嘧啶胺 | 1394076-92-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 5-[6-(3-甲氧基-3-氧杂环丁基)-7-甲基-4-(4-吗啉基)噻吩并[3,2-d]嘧啶-2-基]-2-嘧啶胺
• 中文别名: PI3K/MTOR抑制剂(GNE-317)；GNE-317抑制剂；5-[6-(3-甲氧基-3-氧杂环丁基)-7-甲基-4-(4-吗啉基)噻吩并[3,2-D]嘧啶-2-基]-2-嘧啶胺；5-(6-(3-甲氧基氧杂环丁烷-3-基)-7-甲基-4-吗啉基噻吩并[3,2-D]嘧啶-2-基)嘧啶-2-胺
• 英文名称: GNE-317
• 英文别名: 5-(6-(3-methoxyoxetan-3-yl)-7-methyl-4-morpholinothieno[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine；5-[6-(3-methoxyoxetan-3-yl)-7-methyl-4-morpholin-4-ylthieno[3,2-d]pyrimidin-2-yl]pyrimidin-2-amine
• CAS: 1394076-92-6
• 化学式: C₁₉H₂₂N₆O₃S
• 分子量: 414.488
• InChiKey: XOZLHJMDLKDZAL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  137
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  3-(2-chloro-7-methyl-4-morpholinothieno[3,2-d]pyrimidin-6-yl)oxetan-3-ol 在 四(三苯基膦)钯 、 sodium hydride 、 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 20.17h， 生成 5-[6-(3-甲氧基-3-氧杂环丁基)-7-甲基-4-(4-吗啉基)噻吩并[3,2-d]嘧啶-2-基]-2-嘧啶胺
  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

• Methods for treating brain metastases using combinations of anti-P13K and anti-mTOR agents
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：US11318139B2

  公开（公告）日：2022-05-03

  The present invention relates to methods of treating brain metastases using synergistic combinations of anti-PI3K and anti-mTOR therapies. It has also been determined that blocking PI3K and mTOR provides therapeutic benefit for treating brain metastases.

  本发明涉及使用抗PI3K和抗mTOR疗法的协同组合治疗脑转移瘤的方法。还确定了阻断 PI3K 和 mTOR 可为治疗脑转移瘤带来疗效。
• METHODS FOR TREATING BRAIN METASTASES USING COMBINATIONS OF ANTI-P13K AND ANTI-mTOR AGENTS
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：US20190015422A1

  公开（公告）日：2019-01-17

  The present invention relates to methods of treating brain metastases using synergistic combinations of anti-PI3K and anti-mTOR therapies. It has also been determined that blocking PI3K and mTOR provides therapeutic benefit for treating brain metastases.
• Optimized Method for Treating and Curing Arthritis, Diabetes, Multiple Sclerosis and Other Autoimmune Disease
  申请人：Postrel Richard

  公开号：US20190070166A1

  公开（公告）日：2019-03-07

  The present invention teaches a method, system and process for curing, treating and diagnosing arthritis, diabetes and other related autoimmune diseases. By intercepting and mitigating the disease process at the point of origination prevents the disease from developing and stops the lineage of cells causing disease symptoms. This fundamental system addresses cellular events where the immune reaction is emerging thereby preventing advance of the cascade that feeds the disease. Modulating activity of the errant protein at this initiating point in the immune response blocks the autoimmune cascade and prevents formation of secondary and tertiary effects that will characterize the disease. As the cascade progresses, the number of participating enzymes and pathways compounds so that each progression step further from the initiation point requires increasingly complex therapies. Thus, by treating the primary cause, secondary and tertiary symptoms do not appear. This avoids the side effects observed in multi-faceted approaches presently used to manage the disease symptoms rather than disease causation.
• [EN] METHODS FOR TREATING BRAIN METASTASES USING COMBINATIONS OF ANTI-P13K AND ANTI-mTOR AGENTS<br/>[FR] PROCÉDÉS DE TRAITEMENT DE MÉTASTASES CÉRÉBRALES À L'AIDE D'ASSOCIATIONS D'AGENTS ANTI-P13K ET ANTI-mTOR
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2017132235A1

  公开（公告）日：2017-08-03

  The present invention relates to methods of treating brain metastases using synergistic combinations of anti-PI3K and anti-mTOR therapies. It has also been determined that blocking PI3K and mTOR provides therapeutic benefit for treating brain metastases.
• 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.