5-piperazin-1-yl-2-trifluoromethyl-pyrimidine | 845618-07-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 5-piperazin-1-yl-2-trifluoromethyl-pyrimidine
• 英文别名: 5-(Piperazin-1-yl)-2-(trifluoromethyl)pyrimidine；5-piperazin-1-yl-2-(trifluoromethyl)pyrimidine
• CAS: 845618-07-7
• 化学式: C₉H₁₁F₃N₄
• 分子量: 232.208
• InChiKey: CZUABVNANUQTEN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  41
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-(methylsulfonyl)-2-((1,1,1-trifluoropropan-2-yl)oxy)benzoic acid 、 5-piperazin-1-yl-2-trifluoromethyl-pyrimidine 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以33%的产率得到rac-[5-methanesulfonyl-2-(2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-[4-(2-trifluoromethylpyrimidin-5-yl)-piperazin-1-yl]-methanone
  参考文献：
  名称：

  Selective GlyT1 Inhibitors: Discovery of [4-(3-Fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl][5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methylethoxy)phenyl]methanone (RG1678), a Promising Novel Medicine To Treat Schizophrenia

  摘要：

  The GlyT1 transporter has emerged as a key novel target for the treatment of schizophrenia. Herein, we report on the optimization of the 2-alkoxy-5-methylsulfonebenzoylpiperazine class of GlyT1 inhibitors to improve hERG channel selectivity and brain penetration. This effort culminated in the discovery of compound 10a (RG1678), the first potent and selective GlyT1 inhibitor to have a beneficial effect in schizophrenic patients in a phase II clinical trial.

  DOI：

  10.1021/jm100210p
• 作为产物：
  描述：

  4-(2-trifluoromethyl-pyrimidin-5-yl)-piperazine-1-carboxylic acid tert-butyl ester 在 三氟乙酸 、 sodium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 24.0h， 以60 mg的产率得到5-piperazin-1-yl-2-trifluoromethyl-pyrimidine
  参考文献：
  名称：

  Selective GlyT1 Inhibitors: Discovery of [4-(3-Fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl][5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methylethoxy)phenyl]methanone (RG1678), a Promising Novel Medicine To Treat Schizophrenia

  摘要：

  The GlyT1 transporter has emerged as a key novel target for the treatment of schizophrenia. Herein, we report on the optimization of the 2-alkoxy-5-methylsulfonebenzoylpiperazine class of GlyT1 inhibitors to improve hERG channel selectivity and brain penetration. This effort culminated in the discovery of compound 10a (RG1678), the first potent and selective GlyT1 inhibitor to have a beneficial effect in schizophrenic patients in a phase II clinical trial.

  DOI：

  10.1021/jm100210p

文献信息

• Benzoyl-piperazine derivatives
  申请人：Jolidon J. Synese

  公开号：US20050209241A1

  公开（公告）日：2005-09-22

  The invention relates to compounds of formula wherein the substituents are described herein. The compounds may be used in the treatment of illnesses based on the glycine uptake inhibitor, such as psychoses, pain, neurodegenerative disfunction in memory and learning, schizophrenia, dementia and other diseases in which cognitive processes are impaired, such as attention deficit disorders or Alzheimer's disease.

  本发明涉及具有以下通式的化合物 其中取代基如本文所述。这些化合物可用于治疗基于抑制甘氨酸摄取的疾病，如精神疾病、疼痛、记忆和学习方面的神经退行性功能障碍、精神分裂症、痴呆症以及认知过程受损的其他疾病，例如注意力缺陷障碍或阿尔茨海默病。
• [EN] 1- (2-AMINO-BENZOL) -PIPERAZINE DERIVATIVES AS GLYCINE UPTAKE INHIBITORS FOR THE TREATMENT OF PSYCHOSES<br/>[FR] DERIVES DE 1-(2-AMINO-BENZOL)-PIPERAZINE EN TANT QU'INHIBITEURS DE L'ABSORPTION DU GLYCOCOLLE POUR TRAITER DES PSYCHOSES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2005023260A1

  公开（公告）日：2005-03-17

  A compound of formula (I) wherein the substituents are described in claim 1 for the treatment of psychoses, pain, neurodegenerative disfunction in memory and learning, schizophrenia, dementia and other diseases in which cognitive processes are impaired, such as attention deficit disorders or Alzheimer's disease.

  具有式（I）的化合物，其中取代基如权利要求1中所述，用于治疗精神病、疼痛、记忆和学习中的神经退行性功能障碍、精神分裂症、痴呆症以及认知过程受损的其他疾病，如注意力缺陷障碍或阿尔茨海默病。
• [EN] PIPERAZINE WITH OR-SUBSTITUTED PHENYL GROUP AND THEIR USE AS GLYT1 INHIBITORS<br/>[FR] PIPERAZINE AVEC GROUPE PHENYLE SUBSTITUE DE TYPE OR ET LEUR UTILISATION COMME INHIBITEURS DE GLYT1
  申请人：HOFFMANN LA ROCHE

  公开号：WO2005014563A1

  公开（公告）日：2005-02-17

  The invention relates to compounds of formula (I) wherein the substituents are described in claim 1. The compounds may be used in the treatment of illnesses based on the glycine uptake inhibitor, such as psychoses, pain, neurodegenerative disfunction in memory and learning, schizophrenia, dementia and other diseases in which cognitive processes are impaired, such as attention deficit disorders or Alzheimer's disease.

  该发明涉及式（I）化合物，其中取代基如权利要求书中所述。这些化合物可用于治疗基于甘氨酸摄取抑制剂的疾病，如精神病、疼痛、记忆和学习中的神经退行性功能障碍、精神分裂症、痴呆症以及其他认知过程受损的疾病，如注意力缺陷障碍或阿尔茨海默病。
• [EN] MUSCARINIC RECEPTOR 4 ANTAGONISTS AND METHODS OF USE<br/>[FR] ANTAGONISTES DU RÉCEPTEUR MUSCARINIQUE 4 ET PROCÉDÉS D'UTILISATION
  申请人：NEUROCRINE BIOSCIENCES INC

  公开号：WO2021158698A1

  公开（公告）日：2021-08-12

  The present invention relates to compounds of Formula (Ia), pharmaceutically acceptable salts of compounds of Formula (Ia), and pharmaceutical compositions thereof that modulate the activity of the muscarinic acetylcholine receptor M4. Compounds, pharmaceutical salts of compounds, and pharmaceutical compositions of the present invention are directed to methods useful in the treatment or prophylaxis of a neurological disease, disorder, or symptom, and conditions related thereto.

  本发明涉及式(Ia)的化合物，式(Ia)的药用可接受盐，以及调节肌香胆碱受体M4活性的药物组合物。本发明的化合物、化合物的药用盐和药物组合物用于治疗或预防神经系统疾病、紊乱或症状及相关疾病的方法。
• BENZOYL-PIPERAZINE DERIVATIVES
  申请人：Jolidon Synese

  公开号：US20080119486A1

  公开（公告）日：2008-05-22

  The invention relates to compounds of formula wherein the substituents are described herein. The compounds may be used in the treatment of illnesses based on the glycine uptake inhibitor, such as psychoses, pain, neurodegenerative disfunction in memory and learning, schizophrenia, dementia and other diseases in which cognitive processes are impaired, such as attention deficit disorders or Alzheimer's disease.

  本发明涉及化合物的公式，其中取代基如下所述。该化合物可用于治疗基于甘氨酸摄取抑制剂的疾病，例如精神病、疼痛、记忆和学习中的神经退行性功能障碍、精神分裂症、痴呆和其他认知过程受损的疾病，例如注意力缺陷障碍或阿尔茨海默病。