4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde | 1198277-93-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: 4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde
• 英文别名: 1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrrolo[2,3-b]pyridine-3-carbaldehyde
• CAS: 1198277-93-8
• 化学式: C₁₅H₁₇N₃O₂
• 分子量: 271.319
• InChiKey: GYQKEROQTAYBQP-UHFFFAOYSA-N

物化性质

• 沸点：
  500.6±50.0 °C(Predicted)
• 密度：
  1.43±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  47.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-methyl-3-(3-oxo-2,3-dihydro-1-benzofuran-5-yl)urea 、 4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde 在 盐酸 乙醇 、 乙醚 作用下， 以 乙醇 为溶剂， 反应 16.0h， 以to give (Z)-1-(2-((4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)methylene)-3-oxo-2,3-dihydrobenzofuran-5-yl)-3-methylurea (57 mg, 59% yield) mp 247-55 (dec) (begins to soften at 230° C.)的产率得到1-methyl-3-[(2Z)-2-{[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]methylene}-3-oxo-2,3-dihydro-1-benzofuran-5-yl]urea
  参考文献：
  名称：

  3-SUBSTITUTED-1H-PYRROLO[2,3-B]PYRIDINE AND 3-SUBSTITUTED-1H-PYRROLO[3,2-B]PYRIDINE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES

  摘要：

  本发明涉及以下化合物的3-取代-1H-吡咯[2,3-b]吡啶和3-取代-1H-吡咯[3,2-b]吡啶化合物的公式1：或其药学上可接受的盐，其中组成变量如本文所定义，包括该化合物的组合物，并且该化合物的制备方法和使用方法。

  公开号：

  US20090298820A1
• 作为产物：
  描述：

  8-氧杂-3-氮杂双环[3,2,1]辛烷 、 4-bromo-1-methyl-1-H-pyrrolo[2,3-b]pyridine-3-carbaldehyde 在 tris-(dibenzylideneacetone)dipalladium(0) 、 dipotassium hydrogenphosphate 、 2-二环己膦基-2'-(N,N-二甲胺)-联苯 作用下， 以 1,4-二氧六环 为溶剂， 生成 4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde
  参考文献：
  名称：

  4-Substituted-7-azaindoles bearing a ureidobenzofuranone moiety as potent and selective, ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR)

  摘要：

  A series of 5-ureidobenzofuranones was discovered as potent and selective inhibitors of mTOR with good cellular activity. Molecular modeling studies revealed several hydrogen bond interactions of the ureido group with the enzyme at the ATP-binding site. Furthermore, modeling showed that the ureido group is best situated at C-5 of the benzofuranone. Syntheses of 4-ureido and 5-ureidobenzofuranones are presented. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.02.012

文献信息

• [EN] 3-SUBSTITUTED-1H-INDOLE, 3-SUBSTITUTED-1H-PYRROLO[2,3-B]PYRIDINE AND 3-SUBSTITUTED-1H-PYRROLO[3,2-B]PYRIDINE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES<br/>[FR] COMPOSÉS 1H-INDOLE SUBSTITUÉ EN POSITION 3, 1H-PYRROLO[2,3-B]PYRIDINE SUBSTITUÉE EN POSITION 3 ET 1H-PYRROLO[3,2-B]PYRIDINE SUBSTITUÉE EN POSITION 3, LEUR UTILISATION COMME MTOR KINASE ET INHIBITEURS DE LA PI3 KINASE, ET LEURS SYNTHÈSES
  申请人：WYETH LLC

  公开号：WO2010030727A1

  公开（公告）日：2010-03-18

  The invention relates to 3-substituted-1H-indole, 3-substituted-1H-pyrrolo[2,3-b]pyridine, and 3-substituted-1H-pyrrolo[3,2-b]pyridine compounds of the Formula (I): or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds.

  这项发明涉及Formula (I)的3-取代-1H-吲哚、3-取代-1H-吡咯并[2,3-b]吡啶和3-取代-1H-吡咯并[3,2-b]吡啶化合物，或其药学上可接受的盐，其中组成变量如本文所定义，包括这些化合物的组合物，以及制备和使用这些化合物的方法。
• 3-SUBSTITUTED-1H-INDOLE, 3-SUBSTITUTED-1H-PYRROLO[2,3-B]PYRIDINE AND 3-SUBSTITUTED-1H-PYRROLO[3,2-B]PYRIDINE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES
  申请人：Ayral-Kaloustian Semiramis

  公开号：US20100061982A1

  公开（公告）日：2010-03-11

  The invention relates to 3-substituted-1H-indole, 3-substituted-1H-pyrrolo[2,3-b]pyridine, and 3-substituted-1H-pyrrolo[3,2-b]pyridine compounds of the Formula 1: or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds.

  本发明涉及公式1中的3-取代-1H-吲哚、3-取代-1H-吡咯[2,3-b]吡啶和3-取代-1H-吡咯[3,2-b]吡啶化合物，或其药学上可接受的盐，其中组成变量如本文所定义，包括含有该化合物的组合物，以及制备和使用该化合物的方法。
• Discovery and optimization of 2-(4-substituted-pyrrolo[2,3-b]pyridin-3-yl)methylene-4-hydroxybenzofuran-3(2H)-ones as potent and selective ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR)
  作者：Hwei-Ru Tsou、Gloria MacEwan、Gary Birnberg、George Grosu、Matthew G. Bursavich、Joel Bard、Natasja Brooijmans、Lourdes Toral-Barza、Irwin Hollander、Tarek S. Mansour、Semiramis Ayral-Kaloustian、Ker Yu

  DOI：10.1016/j.bmcl.2010.01.135

  日期：2010.4

  Wediscovered 2-(4-substituted-pyrrolo[2,3-b]pyridin-3-yl)methylene-4-hydroxybenzofuran-3(2H)-ones as potent and selective ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR). Since phenolic OH groups pose metabolic liability, one of the two hydroxyl groups was selectively removed. The SAR data showed the structural features necessary for subnanomolar inhibitory activity against mTOR kinase as well as selectivity over PI3K alpha. An X-ray co-crystal structure of one inhibitor with the mTOR-related PI3K gamma revealed the key hydrogen bonding interactions. (C) 2010 Elsevier Ltd. All rights reserved.
• [EN] 3-SUBSTITUTED-1H-PYRROLO[2,3-B]PYRIDINE AND 3-SUBSTITUTED-1H-PYRROLO[3,2-B]PYRIDINE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES<br/>[FR] COMPOSÉS DE 1H-PYRROLO[2,3-B]PYRIDINE SUBSTITUÉE EN POSITION 3 ET COMPOSÉS DE 1H-PYRROLO[3,2-B]PYRIDINE SUBSTITUÉE EN POSITION 3, LEUR UTILISATION EN TANT QU'INHIBITEURS DE KINASE MTOR ET PI3 KINASE, ET LEUR SYNTHÈSES
  申请人：WYETH CORP

  公开号：WO2009155052A1

  公开（公告）日：2009-12-23

  The invention relates to 3-substituted-1 H-pyrrolo[2,3-b]pyridine, and 3-substituted-1 H- pyrrolo[3,2-b]pyridine compounds of the Formula 1: or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds for the treatment of PI3 and mTOR kinase-mediated diseases, e.g. cancer.