3-(6-morpholin-4-yl-9-piperidin-4-yl-9H-purin-2-yl)phenol | 1062205-68-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 3-(6-morpholin-4-yl-9-piperidin-4-yl-9H-purin-2-yl)phenol
• 英文别名: 3-(6-morpholino-9-(piperidin-4-yl)-9H-purin-2-yl)phenol；3-(6-morpholin-4-yl-9-piperidin-4-ylpurin-2-yl)phenol
• CAS: 1062205-68-8
• 化学式: C₂₀H₂₄N₆O₂
• 分子量: 380.45
• InChiKey: ZNNJFEULXHWOFQ-UHFFFAOYSA-N

物化性质

• 沸点：
  545.0±60.0 °C(Predicted)
• 密度：
  1.48±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  88.3
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-吡啶甲醛 、 3-(6-morpholin-4-yl-9-piperidin-4-yl-9H-purin-2-yl)phenol 在 氯化锌 二甲基亚砜 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以to give 40 mg (65% yield) of the title product (MS (ESI) m/z 472.4)的产率得到3-{6-morpholin-4-yl-9-[1-(pyridin-3-ylmethyl)piperidin-4-yl]-9H-purin-2-yl}phenol
  参考文献：
  名称：

  IMIDAZOLOPYRIMIDINE ANALOGS AND THEIR USE AS PI3 KINASE AND MTOR INHIBITORS

  摘要：

  本发明涉及咪唑吡咯啉类似物，制备咪唑吡咯啉类似物的方法，包含咪唑吡咯啉类似物的组合物，以及治疗或预防PI3K相关疾病的方法，包括向需要治疗的对象施用有效量的咪唑吡咯啉类似物。本发明还涉及治疗或预防mTOR相关疾病的方法，包括向需要治疗的对象施用有效量的咪唑吡咯啉类似物。

  公开号：

  US20080233127A1
• 作为产物：
  描述：

  3-(9-(1-benzylpiperidin-4-yl)-6-morpholino-9H-purin-2-yl)phenol 在 10% palladium on carbon 、 氢气 作用下， 以 甲醇 为溶剂， 生成 3-(6-morpholin-4-yl-9-piperidin-4-yl-9H-purin-2-yl)phenol
  参考文献：
  名称：

  Novel purine and pyrazolo[3,4-d]pyrimidine inhibitors of PI3 kinase-α: Hit to lead studies

  摘要：

  Series of purine and pyrazolo[3,4-d] pyrimidine inhibitors of phosphatidylinositol-3-kinases (PI3K) have been prepared. The optimized purine inhibitors show good potency in a PI3K p110 alpha (PI3K-alpha) fluorescence polarization assay with good selectivity versus PI3K p110 gamma (PI3K-gamma) and the mammalian target of rapamycin (mTOR). The related pyrazolo[3,4-d]pyrimidines show potent PI3K-alpha and mTOR inhibition with good selectivity versus PI3K-gamma. Representative compounds showed activity in a cellular proliferation assay against Caco-2 colorectal, LoVo colorectal and PC3MM2 prostate adenocarcinoma cancer cells. Signaling through the PI3K pathway was confirmed via inhibition of phospho-AKT in MDA-361 cells. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.11.051

文献信息

• Novel imidazolopyrimidines as dual PI3-Kinase/mTOR inhibitors
  作者：Aranapakam M. Venkatesan、Christoph M. Dehnhardt、Zecheng Chen、Efren Delos Santos、Osvaldo Dos Santos、Matthew Bursavich、Adam M. Gilbert、John W. Ellingboe、Semiramis Ayral-Kaloustian、Gulnaz Khafizova、Natasja Brooijmans、Robert Mallon、Irwin Hollander、Larry Feldberg、Judy Lucas、Ker Yu、Jay Gibbons、Robert Abraham、Tarek S. Mansour

  DOI：10.1016/j.bmcl.2009.11.057

  日期：2010.1

  This article describes the syntheses and SAR of a series of imidazolopyrimidine derivatives, which are evaluated as inhibitors of PI3-Kinase (PI3 K) and mTOR. These compounds were found to be ATP competitive with good tumor cell growth inhibition, and suppression of pathway specific biomakers such as phosphorylation of Akt at T308. (C) 2009 Elsevier Ltd. All rights reserved.
• [EN] IMIDAZOLOPYRIMIDINE ANALOGS AND THEIR USE AS PI3 KINASE AND MTOR INHIBITORS<br/>[FR] ANALOGUES D'IMIDAZOLOPYRIMIDINE ET LEUR UTILISATION COMME INHIBITEURS DE PI3 KINASE ET DE MTOR
  申请人：WYETH CORP

  公开号：WO2008116129A2

  公开（公告）日：2008-09-25

  [EN] The present invention relates to Imidazolopyrimidine Analogs, methods of making Imidazolopyrimidine Analogs, compositions comprising an Imidazolopyrimidine Analog, and methods for treating or preventing a PI3K-related disorder comprising administering to a subject in need thereof an effective amount of an Imidazolopyrimidine Analog. The invention also relates to methods for treating or preventing mTOR -related disorders comprising administering to a subject in need thereof an effective amount of an Imidazolopyrimidine Analog.
  [FR] La présente invention concerne des angalogues d'imidazolopyrimidine, des procédés de préparation d'analogues d'imidazolopyrimidine, des compositions comprenant un analogue d'imidazolopyrimidine, et des procédés de traitement ou de prévention d'un trouble lié au PI3K comprenant l'administration à un sujet qui en a besoin d'une quantité efficace d'un analogue d'imidazolopyrimidine. L'invention concerne également un procédé de traitement ou de prévention de troubles liés au MTOR comprenant l'administration à un sujet qui en a besoin d'une quantité efficace d'analogue d'imidazolopyrimidine.
• IMIDAZOLOPYRIMIDINE ANALOGS AND THEIR USE AS PI3 KINASE AND MTOR INHIBITORS
  申请人：Bursavich Matthew Gregory

  公开号：US20080233127A1

  公开（公告）日：2008-09-25

  The present invention relates to Imidazolopyrimidine Analogs, methods of making Imidazolopyrimidine Analogs, compositions comprising an Imidazolopyrimidine Analog, and methods for treating or preventing a PI3K-related disorder comprising administering to a subject in need thereof an effective amount of an Imidazolopyrimidine Analog. The invention also relates to methods for treating or preventing mTOR-related disorders comprising administering to a subject in need thereof an effective amount of an Imidazolopyrimidine Analog.

  本发明涉及咪唑吡嘧啶类似物，制备咪唑吡嘧啶类似物的方法，包含咪唑吡嘧啶类似物的组合物，以及治疗或预防PI3K相关疾病的方法，包括向需要的受试者施用有效量的咪唑吡嘧啶类似物。该发明还涉及治疗或预防mTOR相关疾病的方法，包括向需要的受试者施用有效量的咪唑吡嘧啶类似物。
• Novel purine and pyrazolo[3,4-d]pyrimidine inhibitors of PI3 kinase-α: Hit to lead studies
  作者：Adam M. Gilbert、Pawel Nowak、Natasja Brooijmans、Matthew G. Bursavich、Christoph Dehnhardt、Efren Delos Santos、Larry R. Feldberg、Irwin Hollander、Stephen Kim、Sabrina Lombardi、Kaapjoo Park、Aranapakam M. Venkatesan、Robert Mallon

  DOI：10.1016/j.bmcl.2009.11.051

  日期：2010.1

  Series of purine and pyrazolo[3,4-d] pyrimidine inhibitors of phosphatidylinositol-3-kinases (PI3K) have been prepared. The optimized purine inhibitors show good potency in a PI3K p110 alpha (PI3K-alpha) fluorescence polarization assay with good selectivity versus PI3K p110 gamma (PI3K-gamma) and the mammalian target of rapamycin (mTOR). The related pyrazolo[3,4-d]pyrimidines show potent PI3K-alpha and mTOR inhibition with good selectivity versus PI3K-gamma. Representative compounds showed activity in a cellular proliferation assay against Caco-2 colorectal, LoVo colorectal and PC3MM2 prostate adenocarcinoma cancer cells. Signaling through the PI3K pathway was confirmed via inhibition of phospho-AKT in MDA-361 cells. (C) 2009 Elsevier Ltd. All rights reserved.