2-(3,4-dichloro-phenyl)-isonicotinic acid methyl ester | 445303-06-0

• 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: 2-(3,4-dichloro-phenyl)-isonicotinic acid methyl ester
• 英文别名: methyl 2-(3,4-dichlorophenyl)pyridine-4-carboxylate
• CAS: 445303-06-0
• 化学式: C₁₃H₉Cl₂NO₂
• 分子量: 282.126
• InChiKey: UVBDPEYHXBRBJX-UHFFFAOYSA-N

物化性质

• 沸点：
  410.9±45.0 °C(Predicted)
• 密度：
  1.345±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(3,4-dichloro-phenyl)-isonicotinic acid methyl ester 在 sodium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 16.0h， 生成 2-(3,4-dichlorophenyl)isonicotinic 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：

  2-溴吡啶-4-甲酸甲酯 、 3,4-二氯苯硼酸 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium phosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 2-(3,4-dichloro-phenyl)-isonicotinic acid methyl ester
  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

• Imidazole derivatives
  申请人：——

  公开号：US20020151715A1

  公开（公告）日：2002-10-17

  Novel imidazole derivatives are disclosed. These compounds have a good affinity to the NMDA (N-methyl-D-aspartate)-receptor subtype selective blockers, which have a key function in modulating neuronal activity and plasticity which makes them key players in mediating processes underlying development of CNS as well as learning and memory formation. These compounds are useful in the control or treatment of diseases mediated by this receptor.

  揭示了新型咪唑衍生物。这些化合物对NMDA（N-甲基-D-天冬氨酸）受体亚型选择性阻滞剂具有良好的亲和力，这些受体在调节神经元活动和可塑性中起着关键作用，使它们成为介导中枢神经系统发育以及学习和记忆形成过程的关键因素。这些化合物在控制或治疗由这种受体介导的疾病中很有用。
• IMIDAZOLE DERIVATIVES
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1358165A1

  公开（公告）日：2003-11-05
• US6667335B2
  申请人：——

  公开号：US6667335B2

  公开（公告）日：2003-12-23
• US6610723B2
  申请人：——

  公开号：US6610723B2

  公开（公告）日：2003-08-26
• US6683097B2
  申请人：——

  公开号：US6683097B2

  公开（公告）日：2004-01-27