(1r,4r)-4-(4-(1H-indazol-4-yl)-6-morpholino-1,3,5-triazin-2-yloxy)-N,N-dimethylcyclohexanecarboxamide | 1391925-11-3

• 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: (1r,4r)-4-(4-(1H-indazol-4-yl)-6-morpholino-1,3,5-triazin-2-yloxy)-N,N-dimethylcyclohexanecarboxamide
• CAS: 1391925-11-3
• 化学式: C₂₃H₂₉N₇O₃
• 分子量: 451.528
• InChiKey: NIDQRYIFGQNUHN-WKILWMFISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.28
• 重原子数：
  33.0
• 可旋转键数：
  5.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  109.36
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为产物：
  描述：

  2-(四氢-2H-吡喃-2-基)-4-(4,4,5,5-四甲基-1,3,2-二噁硼烷-2-基)-2H-吲唑 在 四(三苯基膦)钯 、 Oxone 、 甲烷磺酸 、 水 、 sodium carbonate 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 68.0h， 生成 (1r,4r)-4-(4-(1H-indazol-4-yl)-6-morpholino-1,3,5-triazin-2-yloxy)-N,N-dimethylcyclohexanecarboxamide
  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

• NOVEL TRIAZINE COMPOUNDS
  申请人：Sphaera Pharma Pte. Ltd.

  公开号：US20150197515A1

  公开（公告）日：2015-07-16

  The present invention relates to novel triazine compounds of formula (1). The present invention also discloses compounds of formula I along with other pharmaceutical acceptable excipients and use of the compounds to modulate the PI3K/mTOR pathway.

  本发明涉及一种新的三嗪化合物，其化学式为（1）。本发明还揭示了化学式I的化合物，以及其他药用可接受的辅料和使用这些化合物来调节PI3K/mTOR通路的方法。
• [EN] NOVEL TRIAZINE COMPOUNDS<br/>[FR] NOUVEAUX COMPOSÉS DE TRIAZINE
  申请人：SPHAERA PHARMA PTE LTD

  公开号：WO2014016849A9

  公开（公告）日：2014-03-13
• 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