2-methyl-4-(2-methyl-1H-imidazol-4-ylethynyl)pyridine | 761426-39-5

• 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-methyl-4-(2-methyl-1H-imidazol-4-ylethynyl)pyridine
• 英文别名: 2-methyl-4-(2-methyl-1H-imidazol-4-ylethynyl)-pyridine；2-methyl-4-[2-(2-methyl-1H-imidazol-5-yl)ethynyl]pyridine
• CAS: 761426-39-5
• 化学式: C₁₂H₁₁N₃
• 分子量: 197.239
• InChiKey: HHWDTGBZYAEZJM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-氯嘧啶 、 2-methyl-4-(2-methyl-1H-imidazol-4-ylethynyl)pyridine 在 potassium carbonate 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 以50%的产率得到2-[2-methyl-4-(2-methyl-pyridin-4-ylethynyl)-imidazol-1-yl]-pyrimidine
  参考文献：
  名称：

  [EN] IMIDAZOL-4-YL-ETHYNYL-PYRIDINE DERIVATIVES
  [FR] DERIVES DE L'IMIDAZOL-4-YL-ETHYNYL-PYRIDINE

  摘要：

  4-[1-芳基-咪唑-4-基乙炔基]-2-烷基吡啶和1-杂环芳基-咪唑-4-基乙炔基]-2-烷基吡啶衍生物及其药用可接受盐，用于治疗或预防由代谢型谷氨酸受体5完全或部分介导的疾病，例如神经系统的急性、创伤性和慢性退行性过程，如阿尔茨海默病、老年性痴呆、帕金森病、亨廷顿舞蹈症、肌萎缩侧索硬化和多发性硬化，精神疾病如精神分裂症和焦虑、抑郁、疼痛和药物依赖。

  公开号：

  WO2004080998A1
• 作为产物：
  描述：

  2-甲基-4-碘吡啶 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 四丁基氟化铵 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 2-methyl-4-(2-methyl-1H-imidazol-4-ylethynyl)pyridine
  参考文献：
  名称：

  Metabotropic Glutamate Receptor 5 Negative Allosteric Modulators: Discovery of 2-Chloro-4-[1-(4-fluorophenyl)-2,5-dimethyl-1H-imidazol-4-ylethynyl]pyridine (Basimglurant, RO4917523), a Promising Novel Medicine for Psychiatric Diseases

  摘要：

  Negative allosteric modulators (NAMs) of metabotropic glutamate receptor 5 (mGlu5) have potential for the treatment of psychiatric diseases including depression, fragile X syndrome (FXS), anxiety, obsessive-compulsive disorders, and levodopa induced dyskinesia in Parkinson's disease. Herein we report the optimization of a weakly active screening hit 1 to the potent and selective compounds chloro-4-[1-(4-fluorophenyl)-2,5-dimethyl-1H-imidazol-4-ylethynyl]pyridine (basimglurant, 2) and 2-chloro-4-((2,5-dimethyl-1-(4-(trifluoromethoxy)phenyl)-1H-imidazol-4-yl)ethynyl)pyridine (CTEP, 3). Compound 2 is active in a broad range of anxiety tests reaching the same efficacy but at a 10- to 100-fold lower dose compared to diazepam and is characterized by favorable DMPK properties in rat and monkey as well as an excellent preclinical safety profile and is currently in phase II clinical studies for the treatment of depression and fragile X syndrome. Analogue 3 is the first reported mGlu5 NAM with a long half-life in rodents and is therefore an ideal tool compound for chronic studies in mice and rats.

  DOI：

  10.1021/jm501642c

文献信息

• Imidazole derivatives
  申请人：Buettelmann Bernd

  公开号：US20050054686A1

  公开（公告）日：2005-03-10

  The present invention relates to imidazole derivatives of formula I wherein R 1 , R 2 , R 3 , R 4 , X, Y and R are described hereinabove, or a pharmaceutically acceptable salt thereof. The invention also relates to a pharmaceutical composition comprising the imidazole derivatives of formula I, a process for preparing a compound of formula I, and a method of treating or preventing acute and/or chronic neurological disorder comprising administering to a patient in need of such treatment and/or prevention a therapeutically effective amount of said pharmaceutical composition. These disorders include Alzheimer's disease. These disorders also include mild cognitive impairment.

  本发明涉及具有以下式I的咪唑衍生物，其中R1、R2、R3、R4、X、Y和R如上所述，或其药学上可接受的盐。该发明还涉及包括式I的咪唑衍生物的药物组合物，制备式I化合物的方法，以及治疗或预防急性和/或慢性神经系统紊乱的方法，包括向需要此类治疗和/或预防的患者施用所述药物组合物的治疗有效量。这些紊乱包括阿尔茨海默病，也包括轻度认知障碍。
• [EN] IMIDAZOLE DERIVATIVES III<br/>[FR] DERIVES D'IMIDAZOLE .III
  申请人：HOFFMANN LA ROCHE

  公开号：WO2005003117A1

  公开（公告）日：2005-01-13

  The present invention relates to imidazole derivatives of the general formula (I), wherein R1, R2, R3 and R4 are as defined in the description as well as pharmaceutically acceptable salts and processes for the preparation thereof. The invention also relates to medicaments containing said imidazole derivatives and to their use for the manufacture of medicaments for the treatment and prevention of mGluR5 receptor mediated disorders such as acute and/or chronic neurological disorders, in particular anxiety, or for the treatment of chronic and acute pain.

  本发明涉及一般式（I）的咪唑衍生物，其中R1、R2、R3和R4如描述中所定义，以及药学上可接受的盐和制备方法。该发明还涉及含有所述咪唑衍生物的药物以及它们用于制备治疗和预防mGluR5受体介导的疾病的药物，如急性和/或慢性神经系统疾病，尤其是焦虑症，或用于治疗慢性和急性疼痛。
• IMIDAZOLE DERIVATIVES
  申请人：Buettelmann Bernd

  公开号：US20090018171A1

  公开（公告）日：2009-01-15

  The present invention relates to imidazole derivatives of formula I wherein R 1 , R 2 , R 3 , R 4 , X, Y and R are described hereinabove, or a pharmaceutically acceptable salt thereof. The invention also relates to a pharmaceutical composition comprising the imidazole derivatives of formula I, a process for preparing a compound of formula I, and a method of treating or preventing acute and/or chronic neurological disorder comprising administering to a patient in need of such treatment and/or prevention a therapeutically effective amount of said pharmaceutical composition. These disorders include Alzheimer's disease. These disorders also include mild cognitive impairment.

  本发明涉及式I的咪唑衍生物，其中R1、R2、R3、R4、X、Y和R如上所述，或其药学上可接受的盐。本发明还涉及包括式I的咪唑衍生物的制药组合物，制备式I化合物的方法，以及通过向需要该治疗和/或预防的患者施用所述药物组合物的治疗或预防急性和/或慢性神经系统疾病的方法。这些疾病包括阿尔茨海默病和轻度认知障碍。
• IMIDAZOL-4-YL-ETHYNYL-PYRIDINE DERIVATIVES
  申请人：F. Hoffmann-La Roche AG

  公开号：EP1606277B1

  公开（公告）日：2008-05-14
• EP1606277B8
  申请人：——

  公开号：EP1606277B8

  公开（公告）日：2008-10-15