6-[3-chloro-4-(cyclopropylmethoxy)phenyl]pyrimidine-4-carboxylic acid | 1426319-81-4

• 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: 6-[3-chloro-4-(cyclopropylmethoxy)phenyl]pyrimidine-4-carboxylic acid
• 英文别名: 6-[3-Chloro-4-(cyclopropylmethoxy)phenyl]-4-pyrimidinecarboxylic acid
• CAS: 1426319-81-4
• 化学式: C₁₅H₁₃ClN₂O₃
• 分子量: 304.733
• InChiKey: FHITUBQLEKRUQU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  72.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-溴-2-氯苯酚 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 四(三苯基膦)钯 、 potassium acetate 、 potassium carbonate 、 caesium carbonate 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 N,N-二甲基乙酰胺 、 二甲基亚砜 为溶剂， 20.0~150.0 ℃ 、500.01 kPa 条件下， 反应 68.0h， 生成 6-[3-chloro-4-(cyclopropylmethoxy)phenyl]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

文献信息

• [EN] KYNURENINE-3-MONOOXYGENASE INHIBITORS, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE THEREOF<br/>[FR] INHIBITEURS DE KYNURÉNINE-3-MONOOXYGÉNASE, COMPOSITIONS PHARMACEUTIQUES ET PROCÉDÉS D'UTILISATION DE CES COMPOSITIONS
  申请人：COURTNEY STEPHEN MARTIN

  公开号：WO2013033085A1

  公开（公告）日：2013-03-07

  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.

  本文提供了某些化学实体。还提供了包括至少一种化学实体和一种或多种药用载体的药物组合物。描述了治疗对KMO活性抑制敏感的某些疾病和疾病的方法，包括向这些患者投与至少一种化学实体的有效量以减轻疾病或疾病症状的方法。这些疾病包括亨廷顿病等神经退行性疾病。还描述了治疗方法，包括单独使用至少一种化学实体或将至少一种化学实体与一种或多种其他治疗剂结合使用的方法。还提供了筛选能够抑制KMO活性的化合物的方法。
• [EN] METHODS AND COMPOSITIONS FOR TREATING HIV-RELATED DISORDERS<br/>[FR] MÉTHODES ET COMPOSITIONS POUR LE TRAITEMENT DE TROUBLES LIÉS AU VIH
  申请人：CHDI FOUNDATION INC

  公开号：WO2016011316A1

  公开（公告）日：2016-01-21

  Certain adjunctive therapies comprising a kynurenine-3-monooxygenase inhibitor and an antiviral agent for treating HIV-related disorders are provided herein. These disorders include AIDS dementia complex, AIDS-induced encephalopathy, HIV-associated neurocognitive disorder, asymptomatic neurocognitive impairment, minor neurocognitive disorder, minor cognitive motor disorder, vacuolar myelopathy, peripheral neuropathies, and polymyositis. Also provided are pharmaceutical compositions comprising a kynurenine-3- monooxygenase inhibitor and an antiviral agent.

  本文提供了一种治疗HIV相关疾病的特定辅助疗法，包括吲哚酮-3-单加氧酶抑制剂和抗病毒药物。这些疾病包括艾滋病痴呆综合征、艾滋病引起的脑病、HIV相关神经认知障碍、无症状神经认知损害、轻度神经认知障碍、轻度认知运动障碍、空泡性脊髓病、周围神经病变和多发性肌炎。还提供了包含吲哚酮-3-单加氧酶抑制剂和抗病毒药物的药物组合物。
• KYNURENINE-3-MONOOXYGENASE INHIBITORS, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE THEREOF
  申请人：Courtney Stephen Martin

  公开号：US20160251318A1

  公开（公告）日：2016-09-01

  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.

  本文提供了某些化学实体。还提供了包含至少一种化学实体和一个或多个药用载体的制药组合物。描述了治疗对KMO活性抑制有反应的某些疾病和障碍的患者的方法，其中包括向这些患者施用至少一种化学实体的有效量，以减轻疾病或障碍的症状。这些疾病包括神经退行性疾病，如亨廷顿病。还描述了治疗方法，包括单独使用至少一种化学实体作为活性药剂或与一个或多个其他治疗剂联合使用至少一种化学实体。此外，还提供了筛选能够抑制KMO活性的化合物的方法。
• Methods and compositions for treating HIV-related disorders
  申请人：CHDI Foundation, Inc.

  公开号：US10258621B2

  公开（公告）日：2019-04-16

  Certain adjunctive therapies comprising a kynurenine-3-monooxygenase inhibitor and an antiviral agent for treating HIV-related disorders are provided herein. These disorders include AIDS dementia complex, AIDS-induced encephalopathy, HIV-associated neurocognitive disorder, asymptomatic neurocognitive impairment, minor neurocognitive disorder, minor cognitive motor disorder, vacuolar myelopathy, peripheral neuropathies, and polymyositis. Also provided are pharmaceutical compositions comprising a kynurenine-3-monooxygenase inhibitor and an antiviral agent.

  本文提供了某些由犬尿氨酸-3-单氧化酶抑制剂和抗病毒药物组成的辅助疗法，用于治疗艾滋病毒相关疾病。这些疾病包括艾滋病痴呆综合症、艾滋病诱发脑病、HIV 相关神经认知障碍、无症状神经认知障碍、轻微神经认知障碍、轻微认知运动障碍、空泡性脊髓病、周围神经病和多发性肌炎。此外，还提供了包含犬尿氨酸-3-单氧化酶抑制剂和抗病毒剂的药物组合物。
• COMBINATION OF KMO INHIBITOR 6-(3-CHLORO-4-CYCLOPROPOXYPHENYL)PYRIMIDINE-4-CARBOXYLIC ACID WITH ANTIVIRAL AGENT FOR TREATING HIV RELATED NEUROLOGICAL DISORDERS
  申请人：CHDI Foundation, Inc.

  公开号：EP3169684B1

  公开（公告）日：2019-06-26