(3-{7-[(dimethylamino)methyl]-4-morpholin-4-yl-5H-pyrrolo[3,2-d]pyrimidin-2-yl}phenyl)methanol | 1155810-69-7

• 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-{7-[(dimethylamino)methyl]-4-morpholin-4-yl-5H-pyrrolo[3,2-d]pyrimidin-2-yl}phenyl)methanol
• 英文别名: [3-[7-[(dimethylamino)methyl]-4-morpholin-4-yl-5H-pyrrolo[3,2-d]pyrimidin-2-yl]phenyl]methanol
• CAS: 1155810-69-7
• 化学式: C₂₀H₂₅N₅O₂
• 分子量: 367.451
• InChiKey: VXQJPJHEAPEQTG-UHFFFAOYSA-N

物化性质

• 沸点：
  528.3±50.0 °C(predicted)
• 密度：
  1.278±0.06 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：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  77.5
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  聚合甲醛 、 [3-(4-morpholin-4-yl-5H-pyrrolo[3,2-d]pyrimidin-2-yl)phenyl]-methanol 、 二甲胺 在 溶剂黄146 作用下， 以 水 为溶剂， 反应 6.0h， 以64%的产率得到(3-{7-[(dimethylamino)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

• 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.