N-[6-(3,4-dichlorophenyl)pyrimidin-4-yl]methanesulfonamide | 1207723-45-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: N-[6-(3,4-dichlorophenyl)pyrimidin-4-yl]methanesulfonamide
• CAS: 1207723-45-2
• 化学式: C₁₁H₉Cl₂N₃O₂S
• 分子量: 318.183
• InChiKey: YEZFFDXOEALMBX-UHFFFAOYSA-N

物化性质

• 沸点：
  501.1±60.0 °C(Predicted)
• 密度：
  1.547±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  80.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3,4-二氯苯硼酸 在 四(三苯基膦)钯 、 氨 、 sodium hydride 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 26.0h， 生成 N-[6-(3,4-dichlorophenyl)pyrimidin-4-yl]methanesulfonamide
  参考文献：
  名称：

  Development of a Series of Aryl Pyrimidine Kynurenine Monooxygenase Inhibitors as Potential Therapeutic Agents for the Treatment of Huntington’s Disease

  摘要：

  We report on the development of a series of pyrimidine carboxylic acids that are potent and selective inhibitors of kynurenine monooxygenase and competitive for kynurenine. We describe the SAR for this novel series and report on their inhibition of KMO activity in biochemical and cellular assays and their selectivity against other kynurenine pathway enzymes. We describe the optimization process that led to the identification of a program lead compound with a suitable ADME/PK profile for therapeutic development. We demonstrate that systemic inhibition of KMO in vivo with this lead compound provides pharmacodynamic evidence for modulation of kynurenine pathway metabolites both in the periphery and in the central nervous system.

  DOI：

  10.1021/jm501350y

文献信息

• CERTAIN KYNURENINE-3-MONOOXYGENASE INHIBITORS, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE THEREOF
  申请人：CHDI, Inc.

  公开号：EP2331095A1

  公开（公告）日：2011-06-15
• KYNURENINE-3-MONOOXYGENASE INHIBITORS, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE THEREOF
  申请人：Courtney Stephen Martin

  公开号：US20140329795A1

  公开（公告）日：2014-11-06

  Certain chemical entities are provided herein. Also provided are pharmaceutical compositions comprising at least one chemical entity and one or more pharmaceutically acceptable vehicle. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of KMO activity are described, which comprise administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are disclosed. These diseases include neurodegenerative disorders such as Huntington's disease. Also described are methods of treatment include administering at least one chemical entity as a single active agent or administering at least one chemical entity in combination with one or more other therapeutic agents. Also provided are methods for screening compounds capable of inhibiting KMO activity.
• US8536186B2
  申请人：——

  公开号：US8536186B2

  公开（公告）日：2013-09-17
• US9145373B2
  申请人：——

  公开号：US9145373B2

  公开（公告）日：2015-09-29
• US9428464B2
  申请人：——

  公开号：US9428464B2

  公开（公告）日：2016-08-30