4-(2-Fluoro-5-(morpholinomethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine | 1253577-81-9

• 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: 4-(2-Fluoro-5-(morpholinomethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine
• 英文别名: 4-[2-fluoro-5-(morpholin-4-ylmethyl)pyridin-3-yl]-6-methyl-1,3,5-triazin-2-amine
• CAS: 1253577-81-9
• 化学式: C₁₄H₁₇FN₆O
• 分子量: 304.327
• InChiKey: ZAFIYIHYDZKQBJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  90
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-(5-amino-2-chloro-3-pyridinyl)methanesulfonamide 、 4-(2-Fluoro-5-(morpholinomethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine 生成 N-(5-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-(morpholinomethyl)pyridin-2-ylamino)-2-chloropyridin-3-yl)methanesulfonamide
  参考文献：
  名称：

  Synthesis and structure–activity relationships of dual PI3K/mTOR inhibitors based on a 4-amino-6-methyl-1,3,5-triazine sulfonamide scaffold

  摘要：

  Phosphoinositide 3-kinase (PI3K) is an important target in oncology due to the deregulation of the PI3K/Akt signaling pathway in a wide variety of tumors. A series of 4-amino-6-methyl-1,3,5-triazine sulfonamides were synthesized and evaluated as inhibitors of PI3K. The synthesis, in vitro biological activities, pharmacokinetic and in vivo pharmacodynamic profiling of these compounds are described. The most promising compound from this investigation (compound 3j) was found to be a pan class I PI3K inhibitor with a moderate (>10-fold) selectivity over the mammalian target of rapamycin (mTOR) in the enzyme assay. In a U87 MG cellular assay measuring phosphorylation of Akt, compound 3j displayed low double digit nanomolar IC50 and exhibited good oral bioavailability in rats (F-oral = 63%). Compound 3j also showed a dose dependent reduction in the phosphorylation of Akt in a U87 tumor pharmacodynamic model with a plasma EC50 = 193 nM (91 ng/mL). (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.06.078
• 作为产物：
  描述：

  2-Fluoro-5-(morpholinomethyl)pyridin-3-ylboronic acid 、 2-氨基-4-氯-6-甲基-1,3,5-三嗪 在 二氯双[二叔丁基-(4-二甲基氨基苯基)膦]钯(II) 、 potassium acetate 作用下， 以 1,4-二氧六环 为溶剂， 反应 16.0h， 生成 4-(2-Fluoro-5-(morpholinomethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine
  参考文献：
  名称：

  Synthesis and structure–activity relationships of dual PI3K/mTOR inhibitors based on a 4-amino-6-methyl-1,3,5-triazine sulfonamide scaffold

  摘要：

  Phosphoinositide 3-kinase (PI3K) is an important target in oncology due to the deregulation of the PI3K/Akt signaling pathway in a wide variety of tumors. A series of 4-amino-6-methyl-1,3,5-triazine sulfonamides were synthesized and evaluated as inhibitors of PI3K. The synthesis, in vitro biological activities, pharmacokinetic and in vivo pharmacodynamic profiling of these compounds are described. The most promising compound from this investigation (compound 3j) was found to be a pan class I PI3K inhibitor with a moderate (>10-fold) selectivity over the mammalian target of rapamycin (mTOR) in the enzyme assay. In a U87 MG cellular assay measuring phosphorylation of Akt, compound 3j displayed low double digit nanomolar IC50 and exhibited good oral bioavailability in rats (F-oral = 63%). Compound 3j also showed a dose dependent reduction in the phosphorylation of Akt in a U87 tumor pharmacodynamic model with a plasma EC50 = 193 nM (91 ng/mL). (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.06.078

文献信息

• [EN] INHIBITORS OF PI3 KINASE AND / OR MTOR<br/>[FR] INHIBITEURS DE LA PI3 KINASE ET/OU DU MTOR
  申请人：AMGEN INC

  公开号：WO2010126895A1

  公开（公告）日：2010-11-04

  The present invention relates to compounds of Formula I, or a pharmaceutically acceptable salt thereof; methods of treating diseases or conditions, such as cancer, using the compounds; and pharmaceutical compositions containing the compounds, wherein the variables are as defined herein.

  本发明涉及式I的化合物或其药用可接受盐；使用这些化合物治疗疾病或症状的方法，如癌症；以及含有这些化合物的药物组合物，其中变量如本文所定义。
• INHIBITORS OF PI3 KINASE AND/OR MTOR
  申请人：Andrews Kristin

  公开号：US20100273764A1

  公开（公告）日：2010-10-28

  The present invention relates to compounds of Formula I, or a pharmaceutically acceptable salt thereof; methods of treating diseases or conditions, such as cancer, using the compounds; and pharmaceutical compositions containing the compounds, wherein the variables are as defined herein.

  本发明涉及公式I的化合物或其药学上可接受的盐；使用该化合物治疗疾病或病症的方法，如癌症；以及含有该化合物的制药组合物，其中变量在此定义。
• Inhibitors of PI3 kinase and/or mTOR
  申请人：D'Angelo Noel

  公开号：US08362241B2

  公开（公告）日：2013-01-29

  The present invention relates to compounds of Formula I, or a pharmaceutically acceptable salt thereof; methods of treating diseases or conditions, such as cancer, using the compounds; and pharmaceutical compositions containing the compounds, wherein the variables are as defined herein.

  本发明涉及式I化合物或其药学上可接受的盐；使用该化合物治疗疾病或病症的方法，例如癌症；以及含有该化合物的药物组合物，其中变量如本文所定义。
• Inhibitors of PI3 Kinase and/or mTOR
  申请人：Amgen Inc.

  公开号：US20130079303A1

  公开（公告）日：2013-03-28

  The present invention relates to compounds of Formula I, or a pharmaceutically acceptable salt thereof; methods of treating diseases or conditions, such as cancer, using the compounds; and pharmaceutical compositions containing the compounds, wherein the variables are as defined herein.

  本发明涉及公式I的化合物，或其药学可接受的盐；使用这些化合物治疗疾病或病况的方法，如癌症；以及含有这些化合物的药物组合物，其中变量的定义如本文所述。
• INHIBITORS OF PI3 KINASE AND / OR MTOR
  申请人：Amgen, Inc

  公开号：EP2424859A1

  公开（公告）日：2012-03-07