RO-4917523 | 802906-73-6

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: RO-4917523
• 英文别名: 2-chloro-4-((1-(4-fluorophenyl)-2,5-dimethyl-1H-imidazol-4-yl)ethynyl)pyridine；2-chloro-4-((2,5-dimethyl-1-(4-fluorophenyl)-1H-imidazol-4-yl)ethynyl)pyridine；2-chloro-4-{[1-(4-fluorophenyl)-2,5-dimethyl-1H-imidazol-4-yl]ethynyl}pyridine；2-chloro-4-[1-(4-fluorophenyl)-2,5-dimethyl-1H-imidazol-4-ylethynyl]pyridine；2-chloro-4-[1-(4-fluorophenyl)-2-methyl-1H-imidazol-4-ylethynyl]pyridine；basimglurant；2-chloro-4-[2-[1-(4-fluorophenyl)-2,5-dimethylimidazol-4-yl]ethynyl]pyridine
• CAS: 802906-73-6
• 化学式: C₁₈H₁₃ClFN₃
• 分子量: 325.773
• InChiKey: UPZWINBEAHDTLA-UHFFFAOYSA-N

物化性质

• 熔点：
  132 - 135°C
• 沸点：
  526.6±60.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  30.7
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P264,P270,P301+P312,P330
• 危险性描述：
  H302,H315,H320,H335
• 储存条件：
  2-8℃

制备方法与用途

Basimglurant（RG7090）是一种高效、选择性的口服活性mGlu5负变构调节剂，其Kd值为1.1 nM。

反应信息

• 作为反应物：
  描述：

  RO-4917523 在 硫酸 作用下， 以 水 、 异丙醇 为溶剂， 以87.1%的产率得到2-chloro-4-[1-(4-fluorophenyl)-2,5-dimethyl-1H-imidazol-4-ylethynyl]pyridine monohydrosulfate
  参考文献：
  名称：

  [EN] METHODS OF TREATMENT OF TRIGEMINAL NEURALGIA
  [FR] MÉTHODES DE TRAITEMENT DE NÉVRALGIE DU TRIJUMEAU

  摘要：

  本文提供了一种治疗三叉神经痛的方法，即通过向患者施用含有mGlu5负向变构调节剂（NAM）的组合物来治疗患者，该负向变构调节剂具有公式（I）的结构。

  公开号：

  WO2022023519A1
• 作为产物：
  描述：

  2-(2-chloropyridin-4-yl)-1-[1-(4-fluorophenyl)-2,5-dimethyl-1H-imidazol-4-yl]ethanone 在 potassium tert-butylate 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 2.0h， 生成 RO-4917523
  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。
• Imidazole derivatives
  申请人：——

  公开号：US20040248888A1

  公开（公告）日：2004-12-09

  The present invention relates to imidazole derivatives of formula I 1 wherein R 1 , R 2 , R 3 and R 4 are described hereinbelow. These compounds can be used in the treatment or prevention of mGluR5 receptor mediated disorders. These compounds are useful, inter alia, in the treatment or prevention of acute and/or chronic neurological disorders such as psychosis, epilepsy, schizophrenia, Alzheimer' disease, cognititve disorders and memory deficits, as well as chronic and acute pain.

  本发明涉及以下式I1的咪唑衍生物，其中R1、R2、R3和R4如下所述。这些化合物可用于治疗或预防mGluR5受体介导的疾病。这些化合物可用于治疗或预防急性和/或慢性神经系统疾病，如精神病、癫痫、精神分裂症、阿尔茨海默病、认知障碍和记忆缺陷，以及慢性和急性疼痛。
• METHODS FOR THE TREATMENT OF GERD WITH MGLUR5 ANTAGONISTS
  申请人：Jaeschke Georg

  公开号：US20090054490A1

  公开（公告）日：2009-02-26

  The present invention relates to methods for the treatment, prevention and/or delay of progression of gastro-esophageal reflux disease (GERD) by administering compounds that act as antagonists of metabotropic glutamate type-5 receptors (mGluR5 receptor antagonists), for example compounds of formula (I) wherein A, E, R 1 , R 2 , R 2 and R 4 are as defined in the specification.

  本发明涉及通过给予作为代谢型谷氨酸5型受体拮抗剂（mGluR5受体拮抗剂）的化合物来治疗、预防和/或延缓胃食管反流病（GERD）的进展的方法，例如具有以下结构的化合物（I）其中A、E、R1、R2、R3和R4如规范中定义的那样。
• 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。
• IMIDAZOLE DERIVATIVES
  申请人：Buettelmann Bernd

  公开号：US20080103306A1

  公开（公告）日：2008-05-01

  The present invention relates to process for the preparation of an imidazole derivative of formula I, wherein R 1 , R 2 , R 3 and R 4 are described hereinabove. These compounds can be used in the treatment or prevention of mGluR5 receptor mediated disorders. These compounds are useful, inter alia, in the treatment or prevention of acute and/or chronic neurological disorders such as psychosis, epilepsy, schizophrenia, Alzheimer' disease, cognitive disorders and memory deficits, as well as chronic and acute pain.

  本发明涉及制备式I的咪唑衍生物的方法，其中R1、R2、R3和R4如上所述。这些化合物可用于治疗或预防mGluR5受体介导的疾病。这些化合物在治疗或预防急性和/或慢性神经系统疾病，如精神病、癫痫、精神分裂症、阿尔茨海默病、认知障碍和记忆障碍以及慢性和急性疼痛方面是有用的。