1-[4-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)phenyl]-3-pyridazin-4-ylurea | 1197165-79-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-[4-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)phenyl]-3-pyridazin-4-ylurea
• 英文别名: 1-[4-(4,6-Dimorpholin-4-yl-1,3,5-triazin-2-yl)-phenyl]-3-pyridazin-4-ylurea
• CAS: 1197165-79-9
• 化学式: C₂₂H₂₅N₉O₃
• 分子量: 463.499
• InChiKey: BWAPBAYGNOERHW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  131
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  4-氨基哒嗪 、 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以17 mg的产率得到1-[4-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)phenyl]-3-pyridazin-4-ylurea
  参考文献：
  名称：

  Bis(morpholino-1,3,5-triazine) Derivatives: Potent Adenosine 5′-Triphosphate Competitive Phosphatidylinositol-3-kinase/Mammalian Target of Rapamycin Inhibitors: Discovery of Compound 26 (PKI-587), a Highly Efficacious Dual Inhibitor

  摘要：

  The PI3K/Akt signaling pathway is a key pathway in cell proliferation, growth, survival, protein synthesis, and glucose metabolism. It has been recognized recently that inhibiting this pathway might provide a viable therapy for cancer. A series of bis(morpholino-1,3,5-triazine) derivatives were prepared and optimized to provide the highly efficacious PI3K/mTOR inhibitor 1-(4-{[4-(dimethylamino)piperidin-1-yl]carbonyl}phenyl)-3-[4-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)phenyl]urea 26 (PKI-587). Compound 26 has shown excellent activity in vitro and in vivo, with antitumor efficacy in both subcutaneous and orthotopic xenograft tumor models when administered intravenously. The structure activity relationships and the in vitro and in vivo activity of analogues in this series arc described.

  DOI：

  10.1021/jm901830p

文献信息

• TRIAZINE COMPOUNDS AS PI3 KINASE AND MTOR INHIBITORS
  申请人：WYETH LLC

  公开号：US20170119778A1

  公开（公告）日：2017-05-04

  Compounds of formula I wherein: R 1 is and R 2 , R 4 , and R 6-9 are defined herein, and pharmaceutically acceptable salts and esters thereof. These compounds inhibit PI3 kinase and mTOR, and may be used to treat diseases mediated by PI3 kinase and mTOR, such as a variety of cancers. Methods for making and using the compounds of this invention are disclosed. Various compositions containing the compounds of this invention are also disclosed.

  式I化合物，其中：R1为，R2、R4和R6-9如本文所定义，以及其药学上可接受的盐和酯。这些化合物抑制PI3激酶和mTOR，并可用于治疗由PI3激酶和mTOR介导的疾病，例如多种癌症。本发明还公开了制备和使用这些化合物的方法。此外，还公开了含有本发明化合物的各种组合物。
• [EN] TRIAZINE COMPOUNDS AS P13 KINASE AND MTOR INHIBITORS<br/>[FR] COMPOSÉS TRIAZINES EN TANT QU'INHIBITEURS DE KINASE P13 ET DE MTOR
  申请人：WYETH CORP

  公开号：WO2009143313A1

  公开（公告）日：2009-11-26

  Compounds of formula I (I) wherein: R1 is (II) or (III); and R2, R4, and R6-9 are defined herein, and pharmaceutically acceptable salts and esters thereof. These compounds inhibit PI3 kinase and mTOR, and may be used to treat diseases mediated by PI3 kinase and mTOR, such as a variety of cancers. Methods for making and using the compounds of this invention are disclosed. Various compositions containing the compounds of this invention are also disclosed.

  式I的化合物（I）其中：R1为（II）或（III）; R2、R4和R6-9在此定义，并且其药学上可接受的盐和酯。这些化合物抑制PI3激酶和mTOR，并可用于治疗由PI3激酶和mTOR介导的疾病，如各种癌症。公开了制备和使用本发明化合物的各种方法。还公开了含有本发明化合物的各种组合物。
• Triazine compounds as PI3 kinase and mTOR inhibitors
  申请人：WYETH LLC

  公开号：US10022381B2

  公开（公告）日：2018-07-17

  Compounds of formula I wherein: R1 is and R2, R4, and R6-9 are defined herein, and pharmaceutically acceptable salts and esters thereof. These compounds inhibit PI3 kinase and mTOR, and may be used to treat diseases mediated by PI3 kinase and mTOR, such as a variety of cancers. Methods for making and using the compounds of this invention are disclosed. Various compositions containing the compounds of this invention are also disclosed.

  式 I 的化合物 其中 R1 是 和 R2、R4 和 R6-9 在本文中定义，及其药学上可接受的盐和酯。这些化合物抑制 PI3 激酶和 mTOR，可用于治疗由 PI3 激酶和 mTOR 介导的疾病，如各种癌症。本发明公开了制造和使用本发明化合物的方法。还公开了含有本发明化合物的各种组合物。
• TRIAZINE COMPOUNDS AS P13 KINASE AND MTOR INHIBITORS
  申请人：Wyeth LLC

  公开号：EP2294072A1

  公开（公告）日：2011-03-16
• JP2011522802A
  申请人：——

  公开号：JP2011522802A

  公开（公告）日：2011-08-04