3-((4-methyl-6-morpholino-5-nitropyrimidin-2-yl)phenyl)methanol | 1155810-57-3

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 3-((4-methyl-6-morpholino-5-nitropyrimidin-2-yl)phenyl)methanol
• CAS: 1155810-57-3
• 化学式: C₁₆H₁₈N₄O₄
• 分子量: 330.343
• InChiKey: CDKZTTYWBUNXOB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.69
• 重原子数：
  24.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  101.62
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  3-((4-methyl-6-morpholino-5-nitropyrimidin-2-yl)phenyl)methanol 、 N,N-二甲基甲酰胺二甲基缩醛 以 N,N-二甲基甲酰胺 为溶剂， 生成
  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
• 作为产物：
  描述：

  2-chloro-4-methyl-6-morpholino-5-nitropyrimidine 、 3-羟甲基苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 0.5h， 生成 3-((4-methyl-6-morpholino-5-nitropyrimidin-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