2-(6-morpholino-9H-purin-2-yl)phenol | 1062203-80-8

• 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: 2-(6-morpholino-9H-purin-2-yl)phenol
• 英文别名: 2-(6-morpholin-4-yl-9H-purin-2-yl)phenol；2-(6-morpholin-4-yl-7H-purin-2-yl)phenol
• CAS: 1062203-80-8
• 化学式: C₁₅H₁₅N₅O₂
• 分子量: 297.316
• InChiKey: SWYYAXGUDZLFKO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  87.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-(2-氯-9H-嘌呤-6-基)吗啡 、 2-羟基苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-(6-morpholino-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

• 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。
• 10.3390/molecules29112543
  作者：Areias, Filipe、Correia, Carla、Rocha, Ashly、Teixeira, Sofia、Castro, Marián、Brea, Jose、Hu, Huabin、Carlsson, Jens、Loza, Maria I.、Proença, M. Fernanda、Carvalho, M. Alice

  DOI：10.3390/molecules29112543

  日期：——

  A set of 2-aryl-9-H or methyl-6-morpholinopurine derivatives were synthesized and assayed through radioligand binding tests at human A1, A2A, A2B, and A3 adenosine receptor subtypes. Eleven purines showed potent antagonism at A1, A3, dual A1/A2A, A1/A2B, or A1/A3 adenosine receptors. Additionally, three compounds showed high affinity without selectivity for any specific adenosine receptor. The structure-activity

  合成了一组 2-芳基-9-H 或甲基-6-吗啉嘌呤衍生物，并通过放射性配体结合测试对人 A1、A2A、A2B 和 A3 腺苷受体亚型进行了分析。十一种嘌呤对 A1、A3、双 A1/A2A、A1/A2B 或 A1/A3 腺苷受体显示出有效的拮抗作用。此外，三种化合物显示出对任何特定腺苷受体没有选择性的高亲和力。对这组新化合物建立了构效关系。 9-甲基嘌呤衍生物通常效力较低，但选择性较高，9H-嘌呤衍生物效力较高，但选择性较低。这些化合物可以成为新的生化工具和/或药理学药物的重要来源。
• [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.
• 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.