1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-hydroxyphenyl]-3-(4-chlorophenyl)urea | 839713-94-9

• 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-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-hydroxyphenyl]-3-(4-chlorophenyl)urea
• 英文别名: 1-(3-(4-bromo-1-methyl-1H-pyrazol-5-yl)-4-hydroxyphenyl)-3-(4-chlorophenyl)urea；1-[3-(4-bromo-2-methylpyrazol-3-yl)-4-hydroxyphenyl]-3-(4-chlorophenyl)urea
• CAS: 839713-94-9
• 化学式: C₁₇H₁₄BrClN₄O₂
• 分子量: 421.681
• InChiKey: YVULDVDQRKNGCM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  79.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(2-羟乙基)-吡咯烷 、 1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-hydroxyphenyl]-3-(4-chlorophenyl)urea 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以57%的产率得到1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-3-(4-chloro-phenyl)-urea
  参考文献：
  名称：

  3-Phenyl-pyrazole derivatives as modulators of the 5-HT2a serotonin receptor useful for the treatment of disorders related thereto

  摘要：

  本发明涉及某些3-苯基-吡唑衍生物，其具有公式(Ia)和调节5-HT2A血清素受体活性的药物组合物。这些化合物及其药物组合物用于治疗血小板聚集、冠状动脉疾病、心肌梗死、短暂性脑缺血发作、心绞痛、中风、房颤、降低血块形成风险、哮喘或其症状、激动或症状、行为障碍、药物诱导的精神病、兴奋性精神病、抽动秽语综合征、躁狂症、有机或NOS精神病、精神疾病、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，以及睡眠障碍、糖尿病相关障碍、进行性多灶性脑白质病等。本发明还涉及与其他药物一起或分别给药治疗5-HT2A血清素受体介导的疾病的方法。

  公开号：

  US20070207994A1
• 作为产物：
  描述：

  1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxyphenyl]-3-(4-chlorophenyl)urea 在 aluminum (III) chloride 作用下， 以 二氯甲烷 为溶剂， 生成 1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-hydroxyphenyl]-3-(4-chlorophenyl)urea
  参考文献：
  名称：

  [EN] DIARYL AND ARYLHETEROARYL UREA DERIVATIVES AS MODULATORS OF THE 5-HT2A SEROTONIN RECEPTOR USEFUL FOR THE PROPHYLAXIS AND TREATMENT OF DISORDERS RELATED THERTO
  [FR] DERIVES DE DIARYL ET ARYLHETEROARYL UREE UTILISES EN TANT QUE MODULATEURS DU RECEPTEUR DE LA SEROTONINE 5-HT2A UTILES POUR LA PROPHYLAXIE ET LE TRAITEMENT DE TROUBLES ASSOCIES A CE DERNIER

  摘要：

  本发明涉及某些Formula (I)的吡唑衍生物及其药物组合物，可调节5-HT2A 5-羟色胺受体的活性。该类化合物及其药物组合物用于预防或治疗血小板聚集、冠状动脉疾病、心肌梗死、短暂性缺血性发作、心绞痛、中风、心房颤动、减少血凝块形成风险、哮喘或其症状、激动或症状、行为障碍、药物诱导的精神病、兴奋性精神病、吉尔·德·拉·图雷特综合征、躁狂症、器质性或NOS精神病、精神病性障碍、精神病、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、睡眠障碍、睡眠障碍、糖尿病相关疾病等的方法。本发明还涉及预防或治疗5-HT2A 5-羟色胺受体介导的疾病的方法，结合多巴胺D2受体拮抗剂如氟哌啶醇，分别或联合给药。

  公开号：

  WO2005012254A1
• 作为试剂：
  描述：

  1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxyphenyl]-3-(4-chlorophenyl)urea 、 二氯甲烷 、 三氯化铝 在 NaHCO2 、 乙酸乙酯 、 水 、 Brine 、 magnesium sulfate 、 SiO2 、 ethyl acetate n-hexane 、 1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-hydroxyphenyl]-3-(4-chlorophenyl)urea 作用下， 反应 16.0h， 以to provide Compound 58 as a white solid的产率得到1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-hydroxyphenyl]-3-(4-chlorophenyl)urea
  参考文献：
  名称：

  Diaryl and arylheteroaryl urea derivatives as modulators of the 5-HT2A serotonin receptor useful for the prophylaxis and treatment of disorders related thereto

  摘要：

  本发明涉及公式（I）的某些吡唑衍生物及其药物组合物，其调节5-HT2A 5-羟色胺受体的活性。这些化合物和药物组合物用于预防或治疗血小板聚集、冠状动脉疾病、心肌梗死、短暂性脑缺血发作、心绞痛、中风、房颤、减少血栓形成的风险、哮喘或其症状、激动或症状、行为障碍、药物诱导的精神病、兴奋性精神病、Gilles de la 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、睡眠障碍、糖尿病相关疾病等预防或治疗方法。本发明还涉及与多巴胺D2受体拮抗剂（如氟哌啶醇）联合使用的5-HT2A 5-羟色胺受体介导的疾病的预防或治疗方法，可以分别或同时给药。

  公开号：

  US09273035B2

文献信息

• 3-Phenyl-Pyrazole Derivatives as Modulators of the 5-Ht2A Serotonin Receptor Useful for the Treatment of Disorders Related Thereto
  申请人：Teegarden Bradley

  公开号：US20070244086A1

  公开（公告）日：2007-10-18

  The present invention relates to certain 3-phenyl-pyrazole 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 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 a symptom, behavioral disorders, drug induced psychosis, excitative psychosis, Gilles de la Tourette's syndrome, manic disorder, organic or NOS psychosis, psychotic disorder, psychosis, acute schizophrenia, chronic schizophrenia, NOS schizophrenia and related disorders, and sleep disorders, sleep 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.

  本发明涉及某些3-苯基吡唑衍生物（Ia式）及其药物组成物，其调节5-HT2A 5-羟色胺受体的活性。该化合物及其药物组成物针对的方法有用于治疗血小板聚集、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、减少血栓形成风险、哮喘或其症状、激动或症状、行为障碍、药物诱导的精神病、兴奋性精神病、吉尔·德·拉·图雷特综合征、躁狂障碍、器质性或非器质性精神病、精神病、急性精神分裂症、慢性精神分裂症、非特异性精神分裂症及相关疾病、睡眠障碍、糖尿病相关疾病、进行性多灶性白质脑病等。本发明还涉及用于治疗5-HT2A 5-羟色胺受体介导的疾病的方法，该方法与其他药物剂量分别或同时给药。
• 3-phenyl-pyrazole 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：US07884101B2

  公开（公告）日：2011-02-08

  The present invention relates to certain 3-phenyl-pyrazole derivatives of Formula (Ia) and pharmaceutical compositions thereof that modulate the activity of the 5-HT2A serotonin receptor and are useful, optionally in combination with other pharmaceutical agents administered separately or together, in the treatment of 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 a symptom, behavioral disorders, drug induced psychosis, excitative psychosis, Gilles de la Tourette's syndrome, manic disorder, organic or NOS psychosis, psychotic disorder, psychosis, acute schizophrenia, chronic schizophrenia, NOS schizophrenia and related disorders, and sleep disorders, sleep disorders, diabetic-related disorders, progressive multifocal leukoencephalopathy and the like.

  本发明涉及某些3-苯基吡唑衍生物（Ia式）及其制药组合物，其调节5-HT2A 5-羟色胺受体的活性，并可与其他药物单独或联合使用，治疗血小板聚集、冠状动脉疾病、心肌梗死、短暂性缺血性发作、心绞痛、中风、房颤、减少血栓形成的风险、哮喘或其症状、激动或症状、行为障碍、药物诱导的精神病、兴奋性精神病、Gilles de la Tourette综合征、躁狂障碍、器质性或NOS精神病、精神病性障碍、精神病、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、睡眠障碍、糖尿病相关疾病、进行性多灶性白质脑病等。
• 3-PHENYL-PYRAZOLE DERIVATIVES AS MODULATORS OF THE 5-HT2A SEROTONIN RECEPTOR USEFUL FOR THE TREATMENT OF DISORDERS RELATED THERETO
  申请人：Teegarden Bradley

  公开号：US20110105456A1

  公开（公告）日：2011-05-05

  The present invention relates to certain 3-phenyl-pyrazole 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 platelet aggreagation, 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 a symptom, behavioral disorders, drug induced psychosis, excitative psychosis, Gilles de la Tourette's syndrome, manic disorder, organic or NOS psychosis, psychotic disorder, psychosis, acute schizophrenia, chronic schizophrenia, NOS schizophrenia and related disorders, and sleep disorders, sleep 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.

  本发明涉及一些3-苯基吡唑衍生物(Ia式)及其药物组成物，该药物组成物调节5-HT2A血清素受体的活性。该化合物及其药物组成物适用于治疗血小板聚集、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、减少血栓形成的风险、哮喘或其症状、激动或症状、行为障碍、药物诱导的精神病、兴奋性精神病、Gilles de la Tourette综合征、躁狂障碍、器质性或NOS精神病、精神障碍、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、睡眠障碍、糖尿病相关疾病、进行性多发性白质脑病等治疗方法。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，该方法与其他单独或联合使用的药物剂量组合使用。
• DIARYL AND ARYLHETEROARYL UREA DERIVATIVES AS MODULATORS OF THE 5-HT2A SEROTONIN RECEPTOR USEFUL FOR THE PROPHYLAXIS AND TREATMENT OF DISORDERS RELATED THERETO
  申请人：Teegarden Bradley

  公开号：US20150073141A1

  公开（公告）日：2015-03-12

  The present invention relates to certain pyrazole derivatives of Formula (I) 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 prophylaxis or treatment of platelet aggreagation, 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 a symptom, behavioral disorders, drug induced psychosis, excitative psychosis, Gilles de la Tourette's syndrome, manic disorder, organic or NOS psychosis, psychotic disorder, psychosis, acute schizophrenia, chronic schizophrenia, NOS schizophrenia and related disorders, and sleep disorders, sleep disorders, diabetic-related disorders and the like. The present invention also relates to the method of prophylaxis or treatment of 5-HT 2A serotonin receptor mediated disorders in combination with a dopamine D2 receptor antagonist such as haloperidol, administered separately or together.

  本发明涉及公式（I）的某些吡唑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预防或治疗血小板聚集、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、减少血栓形成风险、哮喘或其症状、激动或症状、行为障碍、药物诱导的精神病、兴奋性精神病、Gilles de la Tourette综合征、躁狂障碍、器质性或NOS精神病、精神病性障碍、精神病、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、睡眠障碍、糖尿病相关疾病等预防或治疗方法。本发明还涉及与多巴胺D2受体拮抗剂（如氟哌啶醇）联合使用的5-HT2A 5-羟色胺受体介导疾病的预防或治疗方法，可单独或一起使用。
• Diaryl and arylheteroaryl urea derivatives as modulators of the 5-ht2a serotonin receptor useful for the prophylaxis and treatment of disorders related thereto
  申请人：Arena Pharmaceuticals, Inc.

  公开号：EP1695966A1

  公开（公告）日：2006-08-30

  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. Compounds and pharmaceutical compositions thereof are directed to methods useful in the prophylaxis or treatment of platelet aggreagation, 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 a symptom, behavioral disorders, drug induced psychosis, excitative psychosis, Gilles de la Tourette's syndrome, manic disorder, organic or NOS psychosis, psychotic disorder, psychosis, acute schizophrenia, chronic schizophrenia, NOS schizophrenia and related disorders, and sleep disorders, sleep disorders, diabetic-related disorders and the like. The present invention also relates to the method of prophylaxis or treatment of 5-HT2A serotonin receptor mediated disorders in combination with a dopamine D2 receptor antagonist such as haloperidol, administered separately or together.

  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。其化合物和药物组合物用于预防或治疗血小板聚集、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、降低血栓形成风险、哮喘或其症状、躁动或症状、行为障碍、药物诱发精神病、兴奋性精神病、吉尔-德-图雷特综合征、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，以及睡眠障碍、睡眠紊乱、糖尿病相关疾病等。本发明还涉及5-HT2A血清素受体介导的紊乱的预防或治疗方法，与多巴胺D2受体拮抗剂如氟哌啶醇联合使用，单独或一起给药。