4-chloro-6-m-tolyl-pyrimidine | 884656-80-8

• 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: 4-chloro-6-m-tolyl-pyrimidine
• 英文别名: 4-chloro-6-(3-methylphenyl)pyrimidine
• CAS: 884656-80-8
• 化学式: C₁₁H₉ClN₂
• 分子量: 204.659
• InChiKey: ZFCWMAFLFABZPA-UHFFFAOYSA-N

物化性质

• 沸点：
  333.9±27.0 °C(Predicted)
• 密度：
  1.208±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-chloro-6-m-tolyl-pyrimidine 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 20.0~50.0 ℃ 、500.01 kPa 条件下， 反应 34.0h， 生成 6-(3-methylphenyl)pyrimidine-4-carboxylic acid
  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
• 作为产物：
  描述：

  4,6-二氯嘧啶 、 3-甲基苯硼酸 在 四(三苯基膦)钯 、 potassium carbonate 作用下， 反应 2.0h， 生成 4-chloro-6-m-tolyl-pyrimidine
  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

• Compounds for Nonsense Suppression, and Methods for Their Use
  申请人：Almstead Neil

  公开号：US20080119473A1

  公开（公告）日：2008-05-22

  The present invention relates to methods, compounds, and compositions for treating or preventing diseases associated with nonsense mutations in an mRNA by administering the compounds or compositions of the present invention. More particularly, the present invention relates to methods, compounds, and compositions for suppressing premature translation termination associated with a nonsense mutation in an mRNA.

  本发明涉及使用本发明的化合物或组合物治疗或预防与mRNA中的无义突变相关的疾病的方法、化合物和组合物。更具体地，本发明涉及抑制与mRNA中的无义突变相关的早期翻译终止的方法、化合物和组合物。
• Compounds for nonsense suppression, and methods for their use
  申请人：Almstead Neil

  公开号：US09315467B2

  公开（公告）日：2016-04-19

  The present invention relates to methods, compounds, and compositions for treating or preventing diseases associated with nonsense mutations in an mRNA by administering the compounds or compositions of the present invention. More particularly, the present invention relates to methods, compounds, and compositions for suppressing premature translation termination associated with a nonsense mutation in an mRNA.

  本发明涉及一种治疗或预防与mRNA中无意义突变相关的疾病的方法、化合物和组合物，通过给予本发明的化合物或组合物进行治疗。更具体地说，本发明涉及一种抑制mRNA中无意义突变引起的早期翻译终止的方法、化合物和组合物。
• WO2006/44505
  申请人：——

  公开号：——

  公开（公告）日：——
• COMPOUNDS FOR NONSENSE SUPPRESSION, AND METHODS FOR THEIR USE
  申请人：PTC Therapeutics, Inc.

  公开号：EP1799212A2

  公开（公告）日：2007-06-27
• US9315467B2
  申请人：——

  公开号：US9315467B2

  公开（公告）日：2016-04-19