3-(4-amino-6-morpholino-1,3,5-triazin-2-yl)phenol | 1391925-06-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三嗪类
• 英文名称: 3-(4-amino-6-morpholino-1,3,5-triazin-2-yl)phenol
• 英文别名: 3-(4-Amino-6-morpholin-4-yl-1,3,5-triazin-2-yl)phenol；3-(4-amino-6-morpholin-4-yl-1,3,5-triazin-2-yl)phenol
• CAS: 1391925-06-6
• 化学式: C₁₃H₁₅N₅O₂
• 分子量: 273.294
• InChiKey: OVZOBTMBZICRMV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  97.4
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-chloro-6-morpholino-1,3,5-triazin-2-amine 、 3-羟基苯硼酸 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 0.33h， 以65%的产率得到3-(4-amino-6-morpholino-1,3,5-triazin-2-yl)phenol
  参考文献：
  名称：

  Discovery of Novel and Orally Bioavailable Inhibitors of PI3 Kinase Based on Indazole Substituted Morpholino-Triazines

  摘要：

  A new class of potent PI3K alpha inhibitors is identified based on aryl substituted morpholino-triazine scaffold. The identified compounds showed not only a high level of enzymatic and cellular potency in nanomolar range but also high oral bioavailability. The three lead molecules (based on their in vitro potency) when evaluated further for in vitro metabolic stability as well as pharmacokinetic profile led to the identification of 26, as a candidate for further development. The IC50 and EC50 value of 26 is 60 and 500 nM, respectively, for PI3Ka enzyme inhibitory activity and ovarian cancer (A2780) cell line. The identified lead also showed a high level of microsomal stability and minimal inhibition activity for CYP3A4, CYP2C19, and CYP2D6 at 10 mu M concentrations. The lead compound 26, demonstrated excellent oral bioavailability with an AUG of 5.2 mu M at a dose of 3 mpk in mice and found to be well tolerated in mice when dosed at 30 mpk BID for 5 days.

  DOI：

  10.1021/acsmedchemlett.5b00322

文献信息

• US9481670B2
  申请人：——

  公开号：US9481670B2

  公开（公告）日：2016-11-01
• Discovery of Novel and Orally Bioavailable Inhibitors of PI3 Kinase Based on Indazole Substituted Morpholino-Triazines
  作者：Sundeep Dugar、Frank P. Hollinger、Dinesh Mahajan、Somdutta Sen、Bilash Kuila、Reena Arora、Yogesh Pawar、Vaibhav Shinde、Mahesh Rahinj、Kamal K. Kapoor、Rahul Bhumkar、Santosh Rai、Rakesh Kulkarni

  DOI：10.1021/acsmedchemlett.5b00322

  日期：2015.12.10

  A new class of potent PI3K alpha inhibitors is identified based on aryl substituted morpholino-triazine scaffold. The identified compounds showed not only a high level of enzymatic and cellular potency in nanomolar range but also high oral bioavailability. The three lead molecules (based on their in vitro potency) when evaluated further for in vitro metabolic stability as well as pharmacokinetic profile led to the identification of 26, as a candidate for further development. The IC50 and EC50 value of 26 is 60 and 500 nM, respectively, for PI3Ka enzyme inhibitory activity and ovarian cancer (A2780) cell line. The identified lead also showed a high level of microsomal stability and minimal inhibition activity for CYP3A4, CYP2C19, and CYP2D6 at 10 mu M concentrations. The lead compound 26, demonstrated excellent oral bioavailability with an AUG of 5.2 mu M at a dose of 3 mpk in mice and found to be well tolerated in mice when dosed at 30 mpk BID for 5 days.