1-(2,4-difluorophenyl)-2,5-dimethyl-1H-imidazole-4-carboxylic acid ethyl ester | 871362-60-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(2,4-difluorophenyl)-2,5-dimethyl-1H-imidazole-4-carboxylic acid ethyl ester
• 英文别名: 1-(2,4-Difluoro-phenyl)-2,5-dimethyl-1H-imidazole-4-carboxylic acid ethyl ester；ethyl 1-(2,4-difluorophenyl)-2,5-dimethylimidazole-4-carboxylate
• CAS: 871362-60-6
• 化学式: C₁₄H₁₄F₂N₂O₂
• 分子量: 280.274
• InChiKey: ZPMMKEOJVRLBGO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(2,4-difluorophenyl)-2,5-dimethyl-1H-imidazole-4-carboxylic acid ethyl ester 在 potassium tert-butylate 、 双(三甲基硅烷基)氨基钾 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 3.0h， 生成 2-chloro-4-[1-(2,4-difluorophenyl)-2,5-dimethyl-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
• 作为产物：
  描述：

  2-(羟亚氨基)乙酰乙酸乙酯 在 palladium 10% on activated carbon 、 氢气 、 4-甲基苯磺酸吡啶 、 对甲苯磺酸 、 原乙酸三乙酯 作用下， 以 甲苯 为溶剂， 20.0~75.0 ℃ 、100.0 kPa 条件下， 生成 1-(2,4-difluorophenyl)-2,5-dimethyl-1H-imidazole-4-carboxylic acid ethyl ester
  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

• [EN] PYRIDIN-4-YL-ETHYNYL-IMIDAZOLES AND PYRAZOLES AS MGLU5 RECEPTOR ANTAGONISTS<br/>[FR] PYRIDIN-4-YL-ETHYNYL-IMIDAZOLES ET PYRAZOLES, ANTAGONISTES DU RECEPTEUR MGLUR5
  申请人：HOFFMANN LA ROCHE

  公开号：WO2005118568A1

  公开（公告）日：2005-12-15

  The present invention relates to diazole derivatives of the general formula (I) wherein A, E, R1, Wand R3 are as defined in the claims and description, their use for the preparation of medicaments for treating diseases and processes for preparing them.

  本发明涉及一般式(I)的噻唑烯衍生物，其中A、E、R1、W和R3如权利要求和描述中定义的那样，它们用于制备治疗疾病的药物和制备过程。
• Diazole derivatives
  申请人：Buettelmann Bernd

  公开号：US20060030559A1

  公开（公告）日：2006-02-09

  The present invention relates to diazole derivatives of the general formula wherein A, E, R 1 , R 2 and R 3 are as defined in application and pharmaceutical compositions containing them. The invention also relates to use of such compounds for the treatment of diseases mediated by the metabotropic glutamate receptors (mGluR), such as anxiety, chronic and acute pain, protection against liver damage, urinary incontinence, obesity, Fragile-X and autism, Alzheimer's disease, epilepsy, schizophrenia, ischemia, Huntington's chorea, amyotrophic lateral sclerosis (ALS), dementia caused by AIDs, and Parkinson's disease.

  本发明涉及一般式为的二唑类衍生物，其中A，E，R1，R2和R3如申请中所定义，并且含有它们的药物组合物。本发明还涉及使用这种化合物治疗由代谢型谷氨酸受体（mGluR）介导的疾病，例如焦虑，慢性和急性疼痛，保护肝脏损伤，尿失禁，肥胖症，脆性X和自闭症，阿尔茨海默病，癫痫，精神分裂症，缺血，亨廷顿舞蹈症，肌萎缩性侧索硬化（ALS），由艾滋病引起的痴呆症以及帕金森病。
• DIAZOLE DERIVATIVES
  申请人：Buettelmann Bernd

  公开号：US20100048569A1

  公开（公告）日：2010-02-25

  The present invention relates to diazole derivatives of the general formula wherein A, E, R 1 , R 2 and R 3 are as defined in application and pharmaceutical compositions containing them. The invention also relates to use of such compounds for the treatment of diseases mediated by the metabotropic glutamate receptors (mGluR), such as anxiety, chronic and acute pain, protection against liver damage, urinary incontinence, obesity, Fragile-X and autism, Alzheimer's disease, epilepsy, schizophrenia, ischemia, Huntington's chorea, amyotrophic lateral sclerosis (ALS), dementia caused by AIDs, and Parkinson's disease.

  本发明涉及一般式为的二唑衍生物，其中A、E、R1、R2和R3如申请中所定义，并且包含它们的制药组合物。本发明还涉及使用这种化合物治疗通过代谢型谷氨酸受体（mGluR）介导的疾病，例如焦虑、慢性和急性疼痛、保护肝损伤、尿失禁、肥胖症、脆性X和自闭症、阿尔茨海默病、癫痫、精神分裂症、缺血、亨廷顿舞蹈症、肌萎缩性侧索硬化症（ALS）、由艾滋病引起的痴呆症和帕金森病。
• PYRIDIN-4-YL-ETHYNYL-IMIDAZOLES AND PYRAZOLES AS MGLU5 RECEPTOR ANTAGONISTS
  申请人：F.HOFFMANN-LA ROCHE AG

  公开号：EP1756086A1

  公开（公告）日：2007-02-28
• US8293916B2
  申请人：——

  公开号：US8293916B2

  公开（公告）日：2012-10-23