1-(4-fluoro-phenyl)-2-[4-(5-methyl-2H-pyrazole-3-carbonyl)-piperazin-1-yl]-ethanone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4-fluoro-phenyl)-2-[4-(5-methyl-2H-pyrazole-3-carbonyl)-piperazin-1-yl]-ethanone
• 英文别名: 1-(4-Fluorophenyl)-2-[4-(5-methyl-2H-pyrazole-3-carbonyl)-piperazin-1-yl]ethanone；1-(4-fluorophenyl)-2-[4-(5-methyl-1H-pyrazole-3-carbonyl)piperazin-1-yl]ethanone
• 化学式: C₁₇H₁₉FN₄O₂
• 分子量: 330.362
• InChiKey: KSDRDHTWNXOAEK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  69.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(4-fluoro-phenyl)-2-[4-(5-methyl-2H-pyrazole-3-carbonyl)-piperazin-1-yl]-ethanone 在 N-溴代丁二酰亚胺(NBS) 作用下， 生成 2-[4-(4-bromo-5-methyl-1H-pyrazole-3-carbonyl)piperazin-1-yl]-1-(4-fluorophenyl)ethanone
  参考文献：
  名称：

  Synthesis and in Vivo Evaluation of Phenethylpiperazine Amides: Selective 5-Hydroxytryptamine_2A Receptor Antagonists for the Treatment of Insomnia

  摘要：

  Recent developments in sleep research suggest that antagonism of the serotonin 5-HT2A receptor may improve sleep maintenance insomnia. We herein report the discovery of a series of potent and selective serotonin 5-HT2A receptor antagonists based on a phenethylpiperazine amide core structure. When tested in a rat sleep pharmacology model, these compounds increased both sleep consolidation and deep sleep. Within this series of compounds, an improvement in the metabolic stability of early leads was achieved by introducing a carbonyl group into the phenethylpiperazine linker. Of note, compounds 14 and 27 exhibited potent 5-HT2A receptor binding affinity, high selectivity over the 5-HT2C receptor, favorable CNS partitioning, and good pharmacokinetic and early safety profiles. In vivo, these two compounds showed dose-dependent, statistically significant improvements on deep sleep (delta power) and sleep consolidation at doses as low as 0.1 mg/kg.

  DOI：

  10.1021/jm100479q
• 作为产物：
  描述：

  1-(4-fluorophenyl)-2-(piperazin-1-yl)ethanone hydrochloride 、 5-甲基-1H-吡唑-3-羧酸 在 三乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 四氢呋喃 为溶剂， 反应 0.17h， 以53%的产率得到1-(4-fluoro-phenyl)-2-[4-(5-methyl-2H-pyrazole-3-carbonyl)-piperazin-1-yl]-ethanone
  参考文献：
  名称：

  Synthesis and in Vivo Evaluation of Phenethylpiperazine Amides: Selective 5-Hydroxytryptamine_2A Receptor Antagonists for the Treatment of Insomnia

  摘要：

  Recent developments in sleep research suggest that antagonism of the serotonin 5-HT2A receptor may improve sleep maintenance insomnia. We herein report the discovery of a series of potent and selective serotonin 5-HT2A receptor antagonists based on a phenethylpiperazine amide core structure. When tested in a rat sleep pharmacology model, these compounds increased both sleep consolidation and deep sleep. Within this series of compounds, an improvement in the metabolic stability of early leads was achieved by introducing a carbonyl group into the phenethylpiperazine linker. Of note, compounds 14 and 27 exhibited potent 5-HT2A receptor binding affinity, high selectivity over the 5-HT2C receptor, favorable CNS partitioning, and good pharmacokinetic and early safety profiles. In vivo, these two compounds showed dose-dependent, statistically significant improvements on deep sleep (delta power) and sleep consolidation at doses as low as 0.1 mg/kg.

  DOI：

  10.1021/jm100479q

文献信息

• PYRAZOLE DERIVATIVES AS MODULATORS OF THE 5-HT2A SEROTONIN RECEPTOR USEFUL FOR THE TREATMENT OF DISORDERS RELATED THERETO
  申请人：Xiong Yifeng

  公开号：US20100004264A1

  公开（公告）日：2010-01-07

  Pyrazole derivatives of Formula (Ia) and pharmaceutical compositions thereof that modulate the activity of the serotonin 5HT 2A receptor. Formula (Ia). Compounds and pharmaceutical compositions thereof are directed to methods useful in the treatment of insomnia and related sleep disorders, platelet aggregation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, reducing the risk of blood clot formation, asthma or symptoms thereof, agitation or symptoms thereof, behavioral disorders, drug induced psychosis, excitative psychosis, Gilles de Ia Tourette's syndrome, manic disorder, organic or NOS psychosis, psychotic disorders, psychosis, acute schizophrenia, chronic schizophrenia, NOS schizophrenia and related disorders, diabetic-related disorders, progressive multifocal leukoencephalopathy and the like. The present invention also relates to the methods for the treatment of 5-HT 2A serotonin receptor mediated disorders in combination with other pharmaceutical agents administered separately or together.

  化合物公式（Ia）的吡唑衍生物及其药物组成物可调节5HT2A血清素受体的活性。化合物公式（Ia）及其药物组成物用于治疗失眠和相关睡眠障碍、血小板聚集、冠状动脉疾病、心肌梗死、短暂性脑缺血发作、心绞痛、中风、心房颤动、降低血栓形成的风险、哮喘或其症状、激动或其症状、行为障碍、药物引起的精神病、兴奋性精神病、Gilles de Ia Tourette综合征、躁狂障碍、有机或NOS精神病、精神病性障碍、急性精神分裂症、慢性精神分裂症、NOS精神分裂症及相关障碍、糖尿病相关障碍、进行性多灶性白质脑病等。本发明还涉及联合单独或同时给予其他药物制剂的方法，用于治疗5-HT2A血清素受体介导的疾病。
• Pyrazole derivatives as modulators of the 5-HT2A serotonin receptor useful for the treatment of disorders related thereto
  申请人：Xiong Yifeng

  公开号：US09434692B2

  公开（公告）日：2016-09-06

  Pyrazole derivatives of Formula (Ia) and pharmaceutical compositions thereof that modulate the activity of the serotonin 5HT2A receptor. Formula (Ia). Compounds and pharmaceutical compositions thereof are directed to methods useful in the treatment of insomnia and related sleep disorders, platelet aggregation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, reducing the risk of blood clot formation, asthma or symptoms thereof, agitation or symptoms thereof, behavioral disorders, drug induced psychosis, excitative psychosis, Gilles de Ia Tourette's syndrome, manic disorder, organic or NOS psychosis, psychotic disorders, psychosis, acute schizophrenia, chronic schizophrenia, NOS schizophrenia and related disorders, diabetic-related disorders, progressive multifocal leukoencephalopathy and the like. The present invention also relates to the methods for the treatment of 5-HT2A serotonin receptor mediated disorders in combination with other pharmaceutical agents administered separately or together.

  公式（Ia）的吡唑衍生物及其制药组合物，可调节血清素5HT2A受体的活性。公式（Ia）的化合物和制药组合物用于治疗失眠和相关睡眠障碍，血小板聚集，冠状动脉疾病，心肌梗塞，短暂性缺血性发作，心绞痛，中风，房颤，减少血栓形成风险，哮喘或其症状，激动或其症状，行为障碍，药物诱导的精神病，兴奋性精神病，Gilles de Ia Tourette综合征，躁狂障碍，器质性或NOS精神病，精神病性障碍，急性精神分裂症，慢性精神分裂症，NOS精神分裂症及相关障碍，糖尿病相关障碍，进行性多灶性白质脑病等。本发明还涉及用于治疗5-HT2A血清素受体介导的疾病的方法，该方法与单独或联合使用的其他制药剂量组合。
• Diaryl and arylheteroaryl urea derivatives as modulators of the 5-HT2A serotonin receptor useful for the prophylaxis and treatment of REM sleep behavior disorder
  申请人：Axovant Sciences GmbH

  公开号：US10022355B2

  公开（公告）日：2018-07-17

  The present invention relates to certain pyrazole derivatives of Formula (I) and pharmaceutical compositions thereof that modulate the activity of the 5-HT2A serotonin receptor and their uses for the treatment of REM sleep behavior disorder.

  本发明涉及某些可调节 5-HT2A 血清素受体活性的式 (I) 吡唑衍生物及其药物组合物，以及它们在治疗快速眼动睡眠行为障碍方面的用途。
• Diaryl and arylheteroaryl urea derivatives as modulators of the 5-HT2A serotonin receptor useful for the prophylaxis and treatment of hallucinations associated with a neurodegenerative disease
  申请人：Axovant Sciences GmbH

  公开号：US10034859B2

  公开（公告）日：2018-07-31

  The present invention relates to certain pyrazole derivatives of Formula (I) and pharmaceutical compositions thereof that modulate the activity of the 5-HT2A serotonin receptor and their uses for the treatment and prophylaxis of visual hallucinations associated with Lewy Body dementia.

  本发明涉及某些可调节 5-HT2A 血清素受体活性的式 (I) 吡唑衍生物及其药物组合物，以及它们在治疗和预防路易体痴呆症相关视幻觉方面的用途。
• WO2008/42388
  申请人：——

  公开号：——

  公开（公告）日：——