4-(4-(benzylsulfonyl)-6-(2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-yl)-1,3,5-triazin-2-yl)morpholine | 1391926-35-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 4-(4-(benzylsulfonyl)-6-(2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-yl)-1,3,5-triazin-2-yl)morpholine
• 英文别名: 4-[4-Benzylsulfonyl-6-[2-(oxan-2-yl)indazol-4-yl]-1,3,5-triazin-2-yl]morpholine；4-[4-benzylsulfonyl-6-[2-(oxan-2-yl)indazol-4-yl]-1,3,5-triazin-2-yl]morpholine
• CAS: 1391926-35-4
• 化学式: C₂₆H₂₈N₆O₄S
• 分子量: 520.612
• InChiKey: VCLXBUJBOHPVOL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  121
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4-(4-(benzylsulfonyl)-6-(2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-yl)-1,3,5-triazin-2-yl)morpholine 在 甲烷磺酸 、 水 、 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 生成 3-((4-(1H-indazol-4-yl)-6-morpholino-1,3,5-triazin-2-yl)amino)-N,N-dimethylbenzamide
  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
• 作为产物：
  描述：

  4-硝基吲唑 在 盐酸 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 Oxone 、 四(三苯基膦)钯 、 palladium 10% on activated carbon 、 氢气 、 sodium carbonate 、 三氟乙酸 、 sodium nitrite 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 乙醇 、 水 、 乙酸乙酯 为溶剂， 反应 25.17h， 生成 4-(4-(benzylsulfonyl)-6-(2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-yl)-1,3,5-triazin-2-yl)morpholine
  参考文献：
  名称：

  [EN] NOVEL TRIAZINE COMPOUNDS
  [FR] NOUVEAUX COMPOSÉS DE TRIAZINE

  摘要：

  公开号：

  WO2014016849A9

文献信息

• NOVEL TRIAZINE COMPOUNDS
  申请人：Dugar Sundeep

  公开号：US20130303516A1

  公开（公告）日：2013-11-14

  The present invention relates to novel triazine compounds of formula (1), methods of their preparation, pharmaceutical compositions containing these compounds and the use of these compounds to treat proliferative disorders such as tumors and cancers and also other conditions and disorders related to or associated with dysregulation of PI3 Kinases, PI3 Kinase pathway, mTOR and/or the mTOR pathway.

  本发明涉及公式（1）的新型三嗪类化合物，其制备方法、含有这些化合物的药物组合物以及使用这些化合物治疗增殖性疾病，如肿瘤和癌症，以及与PI3激酶、PI3激酶途径、mTOR和/或mTOR途径失调相关或相关的其他状况和疾病。
• TRIAZINE COMPOUND HAVING PI3K-ALPHA AND MTOR INHIBITING ACTIVITY
  申请人：Sphaera Pharma Pte. Ltd

  公开号：EP2874632B1

  公开（公告）日：2020-06-17
• US9481670B2
  申请人：——

  公开号：US9481670B2

  公开（公告）日：2016-11-01
• US9630958B2
  申请人：——

  公开号：US9630958B2

  公开（公告）日：2017-04-25
• 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.