1-[2-(2,4-difluorophenyl)ethyl]piperazine | 364594-66-1

• 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: 1-[2-(2,4-difluorophenyl)ethyl]piperazine
• CAS: 364594-66-1
• 化学式: C₁₂H₁₆F₂N₂
• 分子量: 226.269
• InChiKey: ALKPXBLADACOTC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-[2-(2,4-difluorophenyl)ethyl]piperazine 、 吡唑并[1,5-a]嘧啶-2-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， 生成 [4-[2-(2,4-Difluorophenyl)ethyl]piperazin-1-yl]-pyrazolo[1,5-a]pyrimidin-2-ylmethanone
  参考文献：
  名称：

  Identification of fused bicyclic heterocycles as potent and selective 5-HT2A receptor antagonists for the treatment of insomnia

  摘要：

  A series of fused bicyclic heterocycles was identified as potent and selective 5-HT2A receptor antagonists. Optimization of the series resulted in compounds that had improved PK properties, favorable CNS partitioning, good pharmacokinetic properties, and significant improvements on deep sleep (delta power) and sleep consolidation. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.080
• 作为产物：
  描述：

  tert-butyl 4-(2,4-difluorophenethyl)piperazine-1-carboxylate 以 盐酸 、 1,4-二氧六环 为溶剂， 反应 1.0h， 以to afford the hydrochloride salt of the title compound (0.718 g) as a pale solid的产率得到
  参考文献：
  名称：

  IMIDAZO[1,2-A]PYRIDINE DERIVATIVES AS MODULATORS OF THE 5-HT2A SEROTONIN RECEPTOR USEFUL FOR THE TREATMENT OF DISORDERS RELATED THERETO

  摘要：

  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。

  公开号：

  US20110263592A1

文献信息

• Phenylsulphonylipiperazinyl derivatives as 5-ht receptor ligands
  申请人：——

  公开号：US20030181464A1

  公开（公告）日：2003-09-25

  A class of phenylsulphonyl derivatives of the following formula (I) wherein Z represents halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, —R a , —OR a , —SR a , —SOR a , —SO 2 R a , —SO 2 NR a R b , —NR a R b , —NR a COR b , —NR a CO 2 R b ; —COR a ; —CO 2 R a or —CONR a R b ; or Z represents an optionally substituted five-membered heteroaromatic ring selected from furan, thiophene, pyrrole, oxazole, thiazole, isoxazole, isothiazole, imidazole, pyrazole, oxadiazole, thiadiazole, triazole and tetrazole; or Z represents an optionally substituted six-membered heteroaromatic ring selected from pyridine, pyrazine, pyrimidine and pyridazine; R a and R b independently represent hydrogen of C 1-6 alkyl, or R a and R b , when linked through a nitrogen atom, together represent the residue of an azetidine, pyrrolidine, piperidine or morpholine ring; E represents a chemical bond or a straight or branched alkylene chain containing from 1 to 4 carbon atoms, optionally incorporating an oxygen atom to form an ether linkage; R 1 represents an optionally substituted aryl(C 2-4 )alkyl group; and R 2 represents hydrogen or halogen, which are selective antagonists of the human 5-HT 2A receptor an are therefore useful as pharmaceutical agents, especially in the treatment and/or prevention of adverse conditions of the central nervous system, including schizophrenia and depression.

  以下式子(I)的苯基磺酰衍生物类，其中Z代表卤素、氰基、硝基、三氟甲基、三氟甲氧基、—Ra、—ORa、—SRa、—SORa、—SO2Ra、—SO2NRaRb、—NRaRb、—NRaCORb、—NRaCO2Rb、—CORa、—CO2Ra或—CONRaRb；或Z代表可选取自呋喃、噻吩、吡咯、噁唑、噻唑、异噁唑、异硫咪唑、咪唑、吡唑、噻二唑、氧嘧啶、硫嘧啶、三唑和四唑的取代五元杂环芳基环；或Z代表可选取自吡啶、吡嗪、嘧啶和吡嗪嗪的取代六元杂环芳基环；Ra和Rb独立地代表氢、C1-6烷基或当通过氮原子连接时，Ra和Rb共同代表氮杂环丙氮、吡咯烷、哌啶或吗啉环的残基；E代表化学键或含有1-4个碳原子的直链或支链烷基链，可选地包含氧原子形成醚键；R1代表可选取代的芳基(C2-4)烷基基团；R2代表氢或卤素，它们是人类5-HT2A受体的选择性拮抗剂，因此在治疗和/或预防中枢神经系统的不良状况，包括精神分裂症和抑郁症方面，是有用的药物。
• 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。
• Phenylsulphonylipiperazinyl derivatives as 5-HT receptor ligands
  申请人：Burkamp Frank

  公开号：US06852718B2

  公开（公告）日：2005-02-08

  A class of phenylsulphonyl derivatives wherein the sulphonyl moiety is also attached to an N-arylalkyl-substituted piperazine ring are selective antagonists of the human 5-HT 2A receptor and are therefore useful as pharmaceutical agents, especially in the treatment and/or prevention of adverse conditions of the central nervous system, including schizophrenia and other psychotic disorders.

  苯磺酰衍生物类化合物，其中磺酰基还连接到一个N-芳基烷基取代的哌嗪环上，是人类5-HT2A受体的选择性拮抗剂，因此可用作药物制剂，特别是用于治疗和/或预防中枢神经系统的不良情况，包括精神分裂症和其他精神障碍。
• 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。
• Imidazo[1,2-α]pyridine derivatives as modulators of the 5-HT2A serotonin receptor useful for the treatment of disorders related thereto
  申请人：Arena Pharmaceuticals, Inc.

  公开号：US10058549B2

  公开（公告）日：2018-08-28

  rmidazo[1,2-α]pyridine derivatives of Formula (Ia) and pharmaceutical compositions thereof that modulate the activity of the 5-HT2A 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-HT2A serotonin receptor mediated disorders in combination with other pharmaceutical agents administered separately or together.

  式（Ia）的咪唑并[1,2-α]吡啶衍生物及其药物组合物，可调节 5-HT2A 血清素受体的活性。其化合物和药物组合物用于治疗失眠、失眠症、副失眠和相关睡眠障碍、血小板聚集、冠状动脉疾病、心肌梗塞、短暂性脑缺血发作、心绞痛、中风、心房颤动、血栓形成、哮喘或其症状、躁动或其症状、行为障碍、药物性精神病、兴奋性精神病、Gilles de Ia Tourette 综合征、躁狂症、器质性或非器质性精神病、精神障碍、精神病、急性精神分裂症、慢性精神分裂症、非器质性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。本发明还涉及与其他药剂单独或联合给药治疗 5-HT2A 血清素受体介导的疾病的方法。