N'-(5-bromo-2-chloro-3-pyridinyl)-N-(2-methoxyethyl)-N-methylsulfamide | 1201845-27-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: N'-(5-bromo-2-chloro-3-pyridinyl)-N-(2-methoxyethyl)-N-methylsulfamide
• 英文别名: 5-Bromo-2-chloro-3-[[2-methoxyethyl(methyl)sulfamoyl]amino]pyridine
• CAS: 1201845-27-3
• 化学式: C₉H₁₃BrClN₃O₃S
• 分子量: 358.644
• InChiKey: NZJKBKRWNHVIEX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  79.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N'-(5-bromo-2-chloro-3-pyridinyl)-N-(2-methoxyethyl)-N-methylsulfamide 在 盐酸 、 tris-(dibenzylideneacetone)dipalladium(0) 、 水 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.83h， 生成 5-Amino-2-chloro-3-[[2-methoxyethyl(methyl)sulfamoyl]amino]pyridine
  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-氯-3-氨基-5-溴吡啶 、 (2-methoxyethyl)(methyl)sulfamoyl chloride 在 4-二甲氨基吡啶 作用下， 以 吡啶 为溶剂， 生成 N'-(5-bromo-2-chloro-3-pyridinyl)-N-(2-methoxyethyl)-N-methylsulfamide
  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

• INHIBITORS OF PI3 KINASE
  申请人：Bo Yunxin Y.

  公开号：US20110092504A1

  公开（公告）日：2011-04-21

  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 Q, X 1 , X 2 , R 1 and Z are as defined herein.

  本发明涉及式（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，例如癌症；以及含有该化合物的制药组合物，其中Q、X1、X2、R1和Z的定义如本文所述。
• [EN] INHIBITORS OF PI3 KINASE<br/>[FR] INHIBITEURS DE LA PI3 KINASE
  申请人：AMGEN INC

  公开号：WO2009155121A3

  公开（公告）日：2010-02-18
• US8415376B2
  申请人：——

  公开号：US8415376B2

  公开（公告）日：2013-04-09