tert-butyl 4-[2-(2,4-difluorophenyl)acetyl]piperazine-1-carboxylate | 364594-65-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl 4-[2-(2,4-difluorophenyl)acetyl]piperazine-1-carboxylate
• 英文别名: tert-Butyl 4-(2-(2,4-Difluorophenyl)acetyl)piperazine-1-carboxylate
• CAS: 364594-65-0
• 化学式: C₁₇H₂₂F₂N₂O₃
• 分子量: 340.37
• InChiKey: DYNFFOWHSAVRSO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-[2-(2,4-difluorophenyl)acetyl]piperazine-1-carboxylate 在 硼烷四氢呋喃络合物 、 甲醇 、 盐酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 3.0h， 以85%的产率得到1-(2,4-difluorophenethyl)piperazine dihydrochloride
  参考文献：
  名称：

  [EN] IMIDAZO[L,2-a]PYRIDINE DERIVATIVES AS MODULATORS OF THE 5-HT2A SEROTONIN RECEPTOR USEFUL FOR THE TREATMENT OF DISORDERS RELATED THERETO
  [FR] DÉRIVÉS D'IMIDAZO[L,2-?]PYRIDINE UTILISÉS COMME MODULATEURS DU RÉCEPTEUR SÉROTONINERGIQUE 5-HT2A DANS LE TRAITEMENT DES TROUBLES QUI LUI SONT ASSOCIÉS

  摘要：

  公开号：

  WO2009023253A3
• 作为产物：
  描述：

  N-Boc-哌嗪 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 8.25h， 生成 tert-butyl 4-[2-(2,4-difluorophenyl)acetyl]piperazine-1-carboxylate
  参考文献：
  名称：

  WO2008/42388

  摘要：

  公开号：

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。
• IMIDAZO[1,2-A]PYRIDINE 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：US20110263592A1

  公开（公告）日：2011-10-27

  Imidazo[1,2-α]pyridine derivatives of Formula (Ia) and pharmaceutical compositions thereof that modulate the activity of the 5-HT 2A serotonin receptor. Compounds and pharmaceutical compositions thereof are directed to methods useful in the treatment of insomnia, dyssomnia, parasomnia and related sleep disorders, platelet aggregation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, thrombosis, 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 methods for the treatment of 5-HT 2A serotonin receptor mediated disorders in combination with other pharmaceutical agents administered separately or together.

  公式（Ia）的咪唑[1,2-α]吡啶衍生物及其制药组合物，可调节5-HT2A 5-羟色胺受体的活性。该化合物及其制药组合物适用于治疗失眠、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、血栓形成、哮喘或其症状、烦躁或其症状、行为障碍、药物诱导的精神病、兴奋性精神病、Gilles de Ia Tourette综合症、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精神分裂症及相关疾病、糖尿病相关疾病、进行性多灶性白质脑病等治疗方法。本发明还涉及与其他药物分别或联合使用治疗5-HT2A 5-羟色胺受体介导的疾病的方法。
• 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。
• Synthesis and in Vivo Evaluation of Phenethylpiperazine Amides: Selective 5-Hydroxytryptamine_2A Receptor Antagonists for the Treatment of Insomnia
  作者：Yifeng Xiong、Brett Ullman、Jin-Sun Karoline Choi、Martin Cherrier、Sonja Strah-Pleynet、Marc Decaire、Peter I. Dosa、Konrad Feichtinger、Bradley R. Teegarden、John M. Frazer、Woo H. Yoon、Yun Shan、Kevin Whelan、Erin K. Hauser、Andrew J. Grottick、Graeme Semple、Hussien Al-Shamma

  DOI：10.1021/jm100479q

  日期：2010.8.12

  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.
• [EN] IMIDAZO[L,2-a]PYRIDINE DERIVATIVES AS MODULATORS OF THE 5-HT2A SEROTONIN RECEPTOR USEFUL FOR THE TREATMENT OF DISORDERS RELATED THERETO<br/>[FR] DÉRIVÉS D'IMIDAZO[L,2-?]PYRIDINE UTILISÉS COMME MODULATEURS DU RÉCEPTEUR SÉROTONINERGIQUE 5-HT2A DANS LE TRAITEMENT DES TROUBLES QUI LUI SONT ASSOCIÉS
  申请人：ARENA PHARM INC

  公开号：WO2009023253A3

  公开（公告）日：2009-04-09