2-(Pyrrolidin-1-yl)-4-(trifluoromethyl)-N-[[4-(trifluoromethyl) phenyl]methyl] pyrimidine-5-carboxamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(Pyrrolidin-1-yl)-4-(trifluoromethyl)-N-[[4-(trifluoromethyl) phenyl]methyl] pyrimidine-5-carboxamide
• 英文别名: 2-(Pyrrolidin-1-yl)-4-(trifluoromethyl)-N-[[4-(trifluoromethyl)phenyl]methyl]pyrimidine-5-carboxamide；2-pyrrolidin-1-yl-4-(trifluoromethyl)-N-[[4-(trifluoromethyl)phenyl]methyl]pyrimidine-5-carboxamide
• 化学式: C₁₈H₁₆F₆N₄O
• 分子量: 418.342
• InChiKey: LKUKGWDNJJHKPV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  58.1
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2-氯-4-(三氟甲基)吡啶-5-羰酰氯 、 碳酸氢钠 、 4-(三氟甲基)苄胺 、 potassium carbonate 、 四氢吡咯 在 2-chloro-4-(trifluoromethyl)-N-[[4-(trifluoromethyl)phenyl]methyl]pyrimidine-5-carboxamide 、 乙腈 作用下， 以 二氯甲烷 为溶剂， 反应 19.0h， 生成 2-(Pyrrolidin-1-yl)-4-(trifluoromethyl)-N-[[4-(trifluoromethyl) phenyl]methyl] pyrimidine-5-carboxamide
  参考文献：
  名称：

  3-fluoro-2-oxindole modulators of KCNQ potassium channels and use thereof in treating migraine and mechanistically related disease

  摘要：

  本发明提供了作为调节剂的化合物，特别是作为人类KCNQ钾通道蛋白或多肽的开放剂，特别是中枢神经系统（CNS）定位的KCNQ钾通道及其异源多聚体，并且这些化合物在治疗偏头痛中的应用。本发明提供的一种新型的钾通道多肽开放剂是氟氧吲哚化合物，首次被描述为治疗偏头痛的治疗剂，通过防止神经元的异步放电。本发明提供的其他KCNQ钾通道开放剂化合物也可用于本发明的治疗方法中，包括2,4-二取代嘧啶-5-羧酰胺衍生物。根据本发明的一个或多个化合物可以单独使用，组合使用，或与其他治疗方法联合使用，以减少、改善和/或缓解偏头痛或类似于偏头痛或机制相关的疾病，例如群发性头痛。

  公开号：

  US06855829B2

文献信息

• Modulators of KCNQ potassium channels and use thereof in treating migraine and mechanistically related diseases
  申请人：——

  公开号：US20020128277A1

  公开（公告）日：2002-09-12

  Compounds which function as modulators, particularly, openers, of human KCNQ potassium channel proteins or polypeptides, particularly, central nervous system (CNS)-located KCNQ potassium channels, and heteromultimers thereof, and their use in the treatment of migraine are provided by the present invention. One novel type of potassium channel polypeptide openers provided by the present invention is the fluorooxindole compounds, described for the first time as therapeutics for the treatment of migraine by preventing the asynchronous firing of neurons. Other KCNQ potassium channel opener compounds that are also useful in the treatments of the invention include 2,4-disubstituted pyrimidine-5-carboxamide derivatives. One or more of the compounds according to the present invention may be utilized alone, in combination, or in conjunction with other treatment modalities for reducing, ameliorating and/or alleviating migraine or diseases similar to, or mechanistically related to, migraine, e.g., cluster headache.

  本发明提供了作为调节剂的化合物，特别是人类KCNQ钾通道蛋白或多肽的开放剂，特别是中枢神经系统（CNS）位于KCNQ钾通道和异源多聚体的开放剂，并且它们在偏头痛治疗中的应用。本发明提供的一种新型钾通道多肽开放剂是氟氧吲哚化合物，首次被描述为治疗偏头痛的治疗剂，通过防止神经元的异步放电。其他KCNQ钾通道开放剂化合物也适用于本发明的治疗，包括2,4-二取代嘧啶-5-羧酰胺衍生物。根据本发明的一个或多个化合物可以单独使用，组合使用，或与其他治疗方法一起使用，以减少，改善和/或缓解偏头痛或类似于偏头痛或机械机制相关的疾病，例如集群头痛。
• MODULATORS OF KCNQ POTASSIUM CHANNELS AND USE THEREOF IN TREATING MIGRAINE AND MECHANISTICALLY RELATED DISEASES
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：EP1441722A2

  公开（公告）日：2004-08-04
• US6855829B2
  申请人：——

  公开号：US6855829B2

  公开（公告）日：2005-02-15
• [EN] MODULATORS OF KCNQ POTASSIUM CHANNELS AND USE THEREOF IN TREATING MIGRAINE AND MECHANISTICALLY RELATED DISEASES<br/>[FR] MODULATEURS DE CANAUX POTASSIQUES KCNQ ET LEUR UTILISATION DANS LE TRAITEMENT DE LA MIGRAINE ET DE MALADIES LIEES A LA MIGRAINE D'UN POINT DE VUE MECANISTIQUE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2002072088A2

  公开（公告）日：2002-09-19

  Compounds which function as modulators, particularly, openers, of human KCNQ potassium channel proteins or polypeptides, particularly, central nervous system(CNS)-located KCNQ potassium channels, and heteromultimers thereof, and their use in the treatment of migraine are provided by the present invention. One novel type of potassium channel polypeptide openers provided by the present invention is the fluorooxindole compounds, described for the first time as therapeutics for the treatment of migraine by preventing the asynchronous firing of neurons. Other KCNQ potassium channel opener compounds that are also useful in the treatments of the invention include 2,4-disubstituted pyrimidine-5-carboxamide derivatives. One or more of the compounds according to the present invention may be utilized alone, in combination, or in conjunction with other treatment modalities for reducing, ameliorating and/or alleviating migraine or diseases similar to, or mechanistically related to, migraine, e.g., cluster headache.
• 3-fluoro-2-oxindole modulators of KCNQ potassium channels and use thereof in treating migraine and mechanistically related disease
  申请人：Dworetzky Steven I.

  公开号：US06855829B2

  公开（公告）日：2005-02-15

  Compounds which function as modulators, particularly, openers, of human KCNQ potassium channel proteins or polypeptides, particularly, central nervous system (CNS)-located KCNQ potassium channels, and heteromultimers thereof, and their use in the treatment of migraine are provided by the present invention. One novel type of potassium channel polypeptide openers provided by the present invention is the fluorooxindole compounds, described for the first time as therapeutics for the treatment of migraine by preventing the asynchronous firing of neurons. Other KCNQ potassium channel opener compounds that are also useful in the treatments of the invention include 2,4-disubstituted pyrimidine-5-carboxamide derivatives. One or more of the compounds according to the present invention may be utilized alone, in combination, or in conjunction with other treatment modalities for reducing, ameliorating and/or alleviating migraine or diseases similar to, or mechanistically related to, migraine, e.g., cluster headache.

  本发明提供了作为调节剂的化合物，特别是作为人类KCNQ钾通道蛋白或多肽的开放剂，特别是中枢神经系统（CNS）定位的KCNQ钾通道及其异源多聚体，并且这些化合物在治疗偏头痛中的应用。本发明提供的一种新型的钾通道多肽开放剂是氟氧吲哚化合物，首次被描述为治疗偏头痛的治疗剂，通过防止神经元的异步放电。本发明提供的其他KCNQ钾通道开放剂化合物也可用于本发明的治疗方法中，包括2,4-二取代嘧啶-5-羧酰胺衍生物。根据本发明的一个或多个化合物可以单独使用，组合使用，或与其他治疗方法联合使用，以减少、改善和/或缓解偏头痛或类似于偏头痛或机制相关的疾病，例如群发性头痛。