2-(4-Nitrophenyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)thieno[3,2-d]pyrimidine-6-carbaldehyde | 1144081-94-6

• 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: 2-(4-Nitrophenyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)thieno[3,2-d]pyrimidine-6-carbaldehyde
• 英文别名: 2-(4-nitrophenyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)thieno[3,2-d]pyrimidine-6-carbaldehyde
• CAS: 1144081-94-6
• 化学式: C₁₉H₁₆N₄O₄S
• 分子量: 396.426
• InChiKey: MVSUZLACYJPIKF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  129
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-甲烷磺酰哌嗪 、 2-(4-Nitrophenyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)thieno[3,2-d]pyrimidine-6-carbaldehyde 在 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 1,2-二氯乙烷 为溶剂， 以54%的产率得到C₂₄H₂₈N₆O₅S₂
  参考文献：
  名称：

  Discovery of 2-arylthieno[3,2-d]pyrimidines containing 8-oxa-3-azabi-cyclo[3.2.1]octane in the 4-position as potent inhibitors of mTOR with selectivity over PI3K

  摘要：

  2-Aryl-4-morpholinothieno[3,2-d]pyrimidines are known PI3K inhibitors. This class of compounds also potently inhibited the homologous enzyme mTOR. Replacement of the morpholine group in these compounds with an 8-oxa-3-azabicyclo[3.2.1]octane group led to mTOR inhibitors with selectivity over PI3K. Optimization of the 2-aryl substituent led to the discovery of 2-(4-ureidophenyl)-thienopyrimidines as highly potent (IC(50) < 1 nM) mTOR inhibitors with excellent selectivity (up to > 1000-fold) over PI3K and good potency in a cellular proliferation assay (IC(50) < 50 nM). (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.10.075
• 作为产物：
  描述：

  C₁₃H₁₂ClN₃O₂S 、 4-硝基苯硼酸频哪醇酯 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 以51%的产率得到2-(4-Nitrophenyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)thieno[3,2-d]pyrimidine-6-carbaldehyde
  参考文献：
  名称：

  Discovery of 2-arylthieno[3,2-d]pyrimidines containing 8-oxa-3-azabi-cyclo[3.2.1]octane in the 4-position as potent inhibitors of mTOR with selectivity over PI3K

  摘要：

  2-Aryl-4-morpholinothieno[3,2-d]pyrimidines are known PI3K inhibitors. This class of compounds also potently inhibited the homologous enzyme mTOR. Replacement of the morpholine group in these compounds with an 8-oxa-3-azabicyclo[3.2.1]octane group led to mTOR inhibitors with selectivity over PI3K. Optimization of the 2-aryl substituent led to the discovery of 2-(4-ureidophenyl)-thienopyrimidines as highly potent (IC(50) < 1 nM) mTOR inhibitors with excellent selectivity (up to > 1000-fold) over PI3K and good potency in a cellular proliferation assay (IC(50) < 50 nM). (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.10.075

文献信息

• THIENOPYRIMIDINE AND PYRAZOLOPYRIMIDINE COMPOUNDS AND THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS
  申请人：Zask Arie

  公开号：US20090098086A1

  公开（公告）日：2009-04-16

  The invention relates to thienopyrimidine and pyrazolopyrimidine compounds of the Formulas (Ia) and (IIa), 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.

  该发明涉及Formula (Ia)和Formula (IIa)的噻吡嘧啶和吡唑嘧啶化合物，或其药用可接受的盐，其中组成变量如本文所定义的那样，包括该化合物的组合物，以及制备和使用该化合物的方法。
• US8129371B2
  申请人：——

  公开号：US8129371B2

  公开（公告）日：2012-03-06
• [EN] THIENOPYRIMIDINE AND PYRAZOLOPYRIMIDINE COMPOUNDS AND THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS<br/>[FR] COMPOSÉS THIÉNOPYRIMIDINE ET PYRAZOLOPYRIMIDINE ET LEUR UTILISATION EN TANT QUE DES INHIBITEURS DE LA KINASE MTOR ET DE LA KINASE PI3
  申请人：WYETH CORP

  公开号：WO2009052145A1

  公开（公告）日：2009-04-23

  The invention relates to thienopyrimidine and pyrazolopyrimidine compounds of the Formulas (Ia) and (IIa), 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.
• Discovery of 2-arylthieno[3,2-d]pyrimidines containing 8-oxa-3-azabi-cyclo[3.2.1]octane in the 4-position as potent inhibitors of mTOR with selectivity over PI3K
  作者：Jeroen C. Verheijen、Ker Yu、Lourdes Toral-Barza、Irwin Hollander、Arie Zask

  DOI：10.1016/j.bmcl.2009.10.075

  日期：2010.1

  2-Aryl-4-morpholinothieno[3,2-d]pyrimidines are known PI3K inhibitors. This class of compounds also potently inhibited the homologous enzyme mTOR. Replacement of the morpholine group in these compounds with an 8-oxa-3-azabicyclo[3.2.1]octane group led to mTOR inhibitors with selectivity over PI3K. Optimization of the 2-aryl substituent led to the discovery of 2-(4-ureidophenyl)-thienopyrimidines as highly potent (IC(50) < 1 nM) mTOR inhibitors with excellent selectivity (up to > 1000-fold) over PI3K and good potency in a cellular proliferation assay (IC(50) < 50 nM). (C) 2009 Elsevier Ltd. All rights reserved.