(3-bromo-4-trifluoromethoxyphenyl)carbamic acid tert-butyl ester | 839715-01-4

• 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: (3-bromo-4-trifluoromethoxyphenyl)carbamic acid tert-butyl ester
• 英文别名: (3-Bromo-4-trifluoromethoxy-phenyl)-carbamic acid tert-butyl ester；tert-butyl N-[3-bromo-4-(trifluoromethoxy)phenyl]carbamate
• CAS: 839715-01-4
• 化学式: C₁₂H₁₃BrF₃NO₃
• 分子量: 356.139
• InChiKey: QAJMRVGJMJHWTH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3-bromo-4-trifluoromethoxyphenyl)carbamic acid tert-butyl ester 在 四(三苯基膦)钯 sodium carbonate 、 N,N-二异丙基乙胺 作用下， 以 甲醚 、 二氯甲烷 、 水 为溶剂， 反应 0.33h， 生成 1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-trifluoromethoxy-phenyl]-3-(2,4-difluoro-phenyl)-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
• 作为产物：
  描述：

  3-溴-4-(三氟甲氧基)苯胺 、 二碳酸二叔丁酯 在 hexanes 作用下， 以 1,4-二氧六环 为溶剂， 反应 16.0h， 以to give (3-bromo-4-trifluoromethoxy-phenyl)-carbamic acid tert-butyl ester as a white solid in 61.0% yield的产率得到(3-bromo-4-trifluoromethoxyphenyl)carbamic acid tert-butyl ester
  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制药组合物，其调节5-HT2A 5-羟色胺受体的活性。这些化合物和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、降低血栓形成风险、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综合症、躁狂障碍、有机或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5-HT2A 5-羟色胺受体介导的疾病的预防或治疗方法，其中与多巴胺D2受体拮抗剂（如氟哌啶醇）联合使用，分别或同时给予。

  公开号：

  US20130237541A1

文献信息

• 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：US20050080124A1

  公开（公告）日：2005-04-14

  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.

  本发明涉及某些式（I）的吡唑衍生物及其药物组合物，该组合物调节5-HT2A血清素受体的活性。该化合物及其药物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、降低血栓形成风险、哮喘或其症状、激动或症状、行为障碍、药物诱导性精神病、兴奋性精神病、Gilles de la Tourette综合症、躁狂障碍、有机或非器质性精神病、精神病性障碍、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、糖尿病相关疾病等预防或治疗的方法。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血清素受体介导的疾病的预防或治疗方法，可以单独或联合使用。
• Biphenyl Derivatives and Their Use in Treating Hepatitis C
  申请人：Wheelhouse Christopher James

  公开号：US20080255105A1

  公开（公告）日：2008-10-16

  A compound which is a biphenyl derivative of formula (I), or a pharmaceutically acceptable salt thereof wherein: R 1 is a C 1 -C 6 alkyl group or a moiety -A 1 , -L 1 -A 1 , -A 1 -A 1 ′, -L 1 -A 1 -A 1 ′, -A 1 -L 1 -A 1 ′, -A 1 -Y 1 -A 1 ′, -A 1 -Het 1 -A 1 ′, -L 1 -A 1 -Y 1 -A 1 ′, -L 1 -A 1 -Het 1 -A 1 ′, -L 1 -Het 1 -A 1 , -L 1 -Y 1 -A 1 , -L 1 -Y 1 -Het 1 -A 1 , -L 1 -Het 1 -Y 1 -A 1 , -L 1 -Y 1 -Het 1 -L 1 ′, -A 1 -Y 1 -Het 1 -A 1 ′, -A 1 -Het 1 -Y 1 -A 1 ′, -A 1 -Het 1 -L 1 -A 1 ′, -A 1 -L 1 -Het 1 -A 1 ′ or -L 1 -Het 1 -L 1 ′; -A and B are the same or different and each represent a direct bond or a —CO—NR′—, —NR′—CO—, —NR′—CO 2 —, —CO—, —NR′—CO—NR″—, —NR′—S(O) 2 —, —S(O) 2 —NR′—, —SO 2 —, —NR′—, —NR′—CO—CO—, —CO—O—, —O—CO—, —(C 1 -C 2 alkylene)-NR′— or —(C 1 -C 2 hydroxyalkylene)-NR′-moiety, wherein R′ and R″ are the same or different and each represent hydrogen or C 1 -C 4 alkyl; —R 2 and R 3 are the same or different and each represent C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy or halogen; n and m are the same or different and each represent 0 or 1; R 4 is a C 1 -C 6 alkyl group or a moiety -A 4 , -L 4 -A 4 , -A 4 -A 4 ′, -L 4 -A 4 -A 4 ′, -A 4 -L 4 -A 4 ′, -A 4 -Y 4 -A 4 ′, -A 4 -Het 4 -A 4 ′, -L 4 -A 4 -Y 4 -A 4 ′, -L 4 -A 4 -Het 4 -A 4 ′, -L 4 -Het 4 -A 4 , -L 4 -Y 4 -A 4 , -L 4 -Y 4 -Het 4 -A 4 , -L 4 -Het 4 -Y 4 -A 4 , -L 4 -Y 4 -Het 4 -L 4 ′, -A 4 -Y 4 -Het 4 -A 4 ′, -A 4 -Het 4 -Y 4 -A 4 ′, -A 4 -Het 4 -L 4 -A 4 ′, -A 4 -L 4 -Het 4 -A 4 ′ or -L 4 -Het 4 -L 4 ′, each A 1 , A 4 , A 1 ′ and A 4 ′ are the same or different and represent a phenyl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocyclyl or C 3 -C 8 carbocyclyl moiety; each L 1 and L 4 is the same or different and represents a C 1 -C 4 alkylene or a C 1 -C 4 hydroxyalkylene group; each Y 1 and Y 4 is the same or different and represents —CO—, —SO— or —S(O) 2 —; each L 1 ′ and L 4 ′ is the same or different and represents hydrogen or a C 1 -C 4 alkyl group; and each Het 1 and Het 4 is the same or different and represents —O—, —S— or —NR′—, wherein R′ is hydrogen or a C 1 -C 4 alkyl group, the phenyl, heteroaryl, heterocyclyl and carbocyclyl moieties in R 1 and R 4 being optionally fused to a phenyl, 5- to 10-membered heteroaryl or 5- to 10-membered heterocyclyl ring; and the phenyl, heteroaryl, heterocyclyl and carbocyclyl moieties in R 1 and R 4 being unsubstituted or substituted by (a) a single unsubstituted substituent selected from —(C 1 -C 4 alkyl)-X 1 , —CO 2 R′, —SO 2 NR′R″, —S(O) 2 —R′, —CONR′R″, —NR′—CO—R′″, —NR′—S(O) 2 —R′″, —CO—NR′—(C 1 -C 4 alkyl)-NR′R″ and —CO—O—(C 1 -C 4 alkyl)-NR′R″ and/or (b) 1, 2 or 3 unsubstituted substituents selected from —(C 1 -C 4 alkyl)-X 2 , halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 hydroxyalkyl, hydroxy, cyano, nitro and —NR′R″, wherein X 1 is —CO 2 R′, —SO 2 —R′, —NR′—CO 2 —R″, —NR′—S(O) 2 —R′″, —CONR′R″ or —SO 2 —NR′R″, each X 2 is the same or different and is cyano, nitro or —NR′R″, each R′ and R″ is the same or different and represents hydrogen or C 1 -C 4 alkyl and each R′″ is the same or different and represents C 1 -C 4 alkyl.

  化合物是公式（I）的二苯基衍生物，或其药学上可接受的盐，其中：R1是C1-C6烷基或基-A1，-L1-A1，-A1-A1'，-L1-A1-A1'，-A1-L1-A1'，-A1-Y1-A1'，-A1-Het1-A1'，-L1-A1-Y1-A1'，-L1-A1-Het1-A1'，-L1-Het1-A1，-L1-Y1-A1，-L1-Y1-Het1-A1，-L1-Het1-Y1-A1，-L1-Y1-Het1-L1'，-A1-Y1-Het1-A1'，-A1-Het1-Y1-A1'，-A1-Het1-L1-A1'，-A1-L1-Het1-A1'或-L1-Het1-L1'的基团；A和B相同或不同，每个代表直接键或-CO-NR'，-NR'-CO，-NR'-CO2，-CO，-NR'-CO-NR"，-NR'-S（O）2，-S（O）2-NR'，-SO2，-NR'，-NR'-CO-CO-，-CO-O-，-O-CO-，-（C1-C2烷基）-NR'或-（C1-C2羟基烷基）-NR'基团，其中R'和R"相同或不同，每个代表氢或C1-C4烷基；-R2和R3相同或不同，每个代表C1-C4烷基，C1-C4烷氧基，C1-C4卤代烷基，C1-C4卤代烷氧基或卤素；n和m相同或不同，每个代表0或1；R4是C1-C6烷基或基-A4，-L4-A4，-A4-A4'，-L4-A4-A4'，-A4-L4-A4'，-A4-Y4-A4'，-A4-Het4-A4'，-L4-A4-Y4-A4'，-L4-A4-Het4-A4'，-L4-Het4-A4，-L4-Y4-A4，-L4-Y4-Het4-A4，-L4-Het4-Y4-A4，-L4-Y4-Het4-L4'，-A4-Y4-Het4-A4'，-A4-Het4-Y4-A4'，-A4-Het4-L4-A4'，-A4-L4-Het4-A4'或-L4-Het4-L4'，每个A1，A4，A1'和A4'相同或不同，代表苯基，5-至10-成员杂芳基，5-至10-成员杂环基或C3-C8碳环基基团；每个L1和L4相同或不同，代表C1-C4烷基或C1-C4羟基烷基基团；每个Y1和Y4相同或不同，代表-CO-，-SO-或-S（O）2-；每个L1'和L4'相同或不同，代表氢或C1-C4烷基基团；每个Het1和Het4相同或不同，代表-O-，-S-或-NR'-，其中R'是氢或C1-C4烷基，R1和R4中的苯基，杂芳基，杂环基和碳环基基团可以选择地与苯基，5-至10-成员杂芳基或5-至10-成员杂环基环融合；R1和R4中的苯基，杂芳基，杂环基和碳环基基团可以未经取代或经过（a）单个未取代的取代基的取代，所选的取代基为-（C1-C4烷基）-X1，-CO2R'，-SO2NR'R"，-S（O）2-R'，-CONR'R"，-NR'-CO-R'"，-NR'-S（O）2-R'"，-CO-NR'（C1-C4烷基）-NR'R"和-CO-O-（C1-C4烷基）-NR'R"和/或（b）1,2或3个未取代的取代基，所选的取代基为-（C1-C4烷基）-X2，卤素，C1-C4烷基，C1-C4烷氧基，C1-C4卤代烷基，C1-C4卤代烷氧基，C1-C4羟基烷基，羟基，氰基，硝基和-NR'R"，其中X1为-CO2R'，-SO2-R'，-NR'-CO2-R"，-NR'-S（O）2-R'"，-CONR'R"或-SO2-NR'R"，每个X2相同或不同，为氰基，硝基或-NR'R"，每个R'和R"相同或不同，代表氢或C1-C4烷基，每个R'"相同或不同，代表C1-C4烷基。
• Biphenyl derivatives and their use in treating hepatitis C
  申请人：AstraZeneca AB

  公开号：US08008303B2

  公开（公告）日：2011-08-30

  Use of a compound which is a biphenyl derivative of formula (I), or a pharmaceutically acceptable salt thereof, for the treatment of Hepatitis C wherein the variables are described herein.

  使用公式（I）的二苯基衍生物化合物或其药学上可接受的盐，用于治疗丙型肝炎，其中变量在此处描述。
• 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。