[3-(5-methyl-4-morpholin-4-yl-5H-pyrrolo[3,2-d]pyrimidin-2-yl)phenyl]methanol | 1155811-29-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: [3-(5-methyl-4-morpholin-4-yl-5H-pyrrolo[3,2-d]pyrimidin-2-yl)phenyl]methanol
• 英文别名: [3-(5-methyl-4-morpholin-4-ylpyrrolo[3,2-d]pyrimidin-2-yl)phenyl]methanol
• CAS: 1155811-29-2
• 化学式: C₁₈H₂₀N₄O₂
• 分子量: 324.382
• InChiKey: BGMKQZPGFKHBEC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  63.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  四氢吡咯 、 聚合甲醛 、 [3-(5-methyl-4-morpholin-4-yl-5H-pyrrolo[3,2-d]pyrimidin-2-yl)phenyl]methanol 以 溶剂黄146 为溶剂， 反应 16.0h， 以to give the title compound as off-white solid (32.8 mg, 26% yield)的产率得到{3-[5-methyl-4-morpholin-4-yl-7-(pyrrolidin-1-ylmethyl)-5Hpyrrolo[3,2-d]pyrimidin-2-yl]phenyl}methanol
  参考文献：
  名称：

  PYRROLO[3,2-d]PYRIMIDINE COMPOUNDS AND THEIR USE AS PI3 KINASE AND mTOR KINASE INHIBITORS

  摘要：

  一种吡咯并[3,2-d]嘧啶化合物，例如公式（I）的化合物：或其药学上可接受的盐，其中组成变量的定义如本文所述，包括该化合物的组合物以及制备和使用该化合物的方法。

  公开号：

  US20090149458A1
• 作为产物：
  描述：

  在 三氟乙酸 、 sodium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 3.0h， 以252 mg的产率得到[3-(5-methyl-4-morpholin-4-yl-5H-pyrrolo[3,2-d]pyrimidin-2-yl)phenyl]methanol
  参考文献：
  名称：

  Synthesis and SAR of Novel 4-Morpholinopyrrolopyrimidine Derivatives as Potent Phosphatidylinositol 3-Kinase Inhibitors

  摘要：

  Significant evidence suggests that deregulation of the PI3K/Akt pathway is important in tumor progression. Mechanisms include loss of function of the tumor suppressor PTEN and high frequency of mutation of the PI3K p110 alpha isoform in human malignancies. This connection between PI3K and tumor genesis makes PI3K a promising target for cancer treatment. A series of 4-morpholinopyrrolopyrimidine derivatives were synthesized and evaluated as inhibitors of PI3K alpha and mTOR, leading to the discovery of PI3K alpha selective inhibitors (e.g., 9) and dual PI3K alpha/mTOR kinase inhibitors (e.g., 46 and 48). PI3K alpha/mTOR dual inhibitors demonstrated inhibition of tumor cell growth in vitro and in vivo and caused suppression of the pathway specific biomarkers [e.g., the phosphorylation of Akt at Thr308 (T308) and Ser473 (S473)] in the human breast cancer cell line MDA361. In addition, compound 46 demonstrated good in vivo efficacy in the MDA361 human breast tumor xenograft model.

  DOI：

  10.1021/jm901783v

文献信息

• PYRROLO[3,2-d]PYRIMIDINE COMPOUNDS AND THEIR USE AS PI3 KINASE AND mTOR KINASE INHIBITORS
  申请人：CHEN Zecheng

  公开号：US20090149458A1

  公开（公告）日：2009-06-11

  A pyrrolo[3,2-d]pyrimidine compound, such as a compound 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.

  一种吡咯并[3,2-d]嘧啶化合物，例如具有以下式（I）的化合物：或其药用可接受的盐，其中构成变量如本文所定义，包括所述化合物的组合物，以及制备和使用所述化合物的方法。
• [EN] PYRROLO[3,2-D]PYRIMIDINE COMPOUNDS AND THEIR USE AS PI3 KINASE AND MTOR KINASE INHIBITORS<br/>[FR] COMPOSÉS DE PYRROLO[3,2-D]PYRIMIDINE ET LEUR UTILISATION COMME INHIBITEURS DE LA PI3 KINASE ET DE LA MTOR KINASE
  申请人：WYETH CORP

  公开号：WO2009070524A1

  公开（公告）日：2009-06-04

  A pyrrolo[3,2-d]pyrimidine compound, such as a compound 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, useful for treating PI3K-related diseases.
• Synthesis and SAR of Novel 4-Morpholinopyrrolopyrimidine Derivatives as Potent Phosphatidylinositol 3-Kinase Inhibitors
  作者：Zecheng Chen、Aranapakam M. Venkatesan、Christoph M. Dehnhardt、Semiramis Ayral-Kaloustian、Natasja Brooijmans、Robert Mallon、Larry Feldberg、Irwin Hollander、Judy Lucas、Ker Yu、Fangming Kong、Tarek S. Mansour

  DOI：10.1021/jm901783v

  日期：2010.4.22

  Significant evidence suggests that deregulation of the PI3K/Akt pathway is important in tumor progression. Mechanisms include loss of function of the tumor suppressor PTEN and high frequency of mutation of the PI3K p110 alpha isoform in human malignancies. This connection between PI3K and tumor genesis makes PI3K a promising target for cancer treatment. A series of 4-morpholinopyrrolopyrimidine derivatives were synthesized and evaluated as inhibitors of PI3K alpha and mTOR, leading to the discovery of PI3K alpha selective inhibitors (e.g., 9) and dual PI3K alpha/mTOR kinase inhibitors (e.g., 46 and 48). PI3K alpha/mTOR dual inhibitors demonstrated inhibition of tumor cell growth in vitro and in vivo and caused suppression of the pathway specific biomarkers [e.g., the phosphorylation of Akt at Thr308 (T308) and Ser473 (S473)] in the human breast cancer cell line MDA361. In addition, compound 46 demonstrated good in vivo efficacy in the MDA361 human breast tumor xenograft model.