3-[2-(trifluoromethyl)-2'-fluoro-4'-bromobenzhydryloxy]-N-(tert-butyl)azetidine-1-carboxamide

• 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-[2-(trifluoromethyl)-2'-fluoro-4'-bromobenzhydryloxy]-N-(tert-butyl)azetidine-1-carboxamide
• 英文别名: 3-[(4-bromo-2-fluorophenyl)-[2-(trifluoromethyl)phenyl]methoxy]-N-tert-butylazetidine-1-carboxamide
• 化学式: C₂₂H₂₃BrF₄N₂O₂
• 分子量: 503.334
• InChiKey: PTVKXSFBTUPKHX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  哌啶 、 3-[2-(trifluoromethyl)-2'-fluoro-4'-bromobenzhydryloxy]-N-(tert-butyl)azetidine-1-carboxamide 在 (acetato-κO)({2-[bis(2-methylphenyl)phosphanyl]phenyl}methyl)palladium 二乙二醇二甲醚 、 potassium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 molybdenum hexacarbonyl 作用下， 以 二乙二醇二甲醚 、 甲苯 为溶剂， 反应 0.25h， 以12%的产率得到3-[2-(trifluoromethyl)-2'-fluoro-4'-(1-piperidinyloxomethyl)-benzhydryloxy]-N-(tert-butyl)azetidine-1-carboxamide
  参考文献：
  名称：

  [EN] AZETIDINECARBOXAMIDE DERIVATIVES AND THEIR USE IN THE TREATMENT OF CB1 RECEPTOR MEDIATED DISORDERS
  [FR] DERIVES D'AZETIDINECARBOXAMIDE ET LEUR UTILISATION DANS LE TRAITEMENT DE TROUBLES MEDIES PAR LES RECEPTEUR CB1

  摘要：

  式(I)化合物及其在治疗中的应用，特别用于治疗由CB1受体介导的疾病，如肥胖症：式(I)中：R1和R2各自独立地选自芳基；R3为氢或烷基；或其药学上可接受的盐或前药，其中R1和R2中至少一个在相对于与[-CH-0-]基团连接点的邻位上具有非氢取代基。

  公开号：

  WO2004096763A1
• 作为产物：
  描述：

  3-[2-(trifluoromethyl)-2'-fluoro-4'-bromobenzhydryloxy]azetidine hydrochloride 、 叔丁基异氰酸酯 、 3-(2,4,4'-trichlorobenzhydryloxy)-N-(tert-butyl)azetidine-1-carboxamide 生成 3-[2-(trifluoromethyl)-2'-fluoro-4'-bromobenzhydryloxy]-N-(tert-butyl)azetidine-1-carboxamide
  参考文献：
  名称：

  Azetidinecarboxamide derivatives and their use in the treatment of cb1 receptor mediated disorders

  摘要：

  公式（I）的化合物及其在治疗中的应用，尤其是用于治疗由CB1受体介导的疾病，如肥胖症：公式（I）中：R1和R2独立地选择自芳基；而R3是氢或烷基；或其药物可接受的盐或前药，其中至少有一个R1和R2在其[—CH—O—]基团的连接点相对于其邻位位置具有非氢取代基。

  公开号：

  US07504522B2

文献信息

• COMPOUNDS WITH A COMBINATION OF CANNABINOID-CB1 ANTAGONISM AND ACETYLCHOLINESTERASE INHIBITION
  申请人：Lange Josephus H.M.

  公开号：US20080153867A1

  公开（公告）日：2008-06-26

  Embodiments of this invention relate to compounds having a combination of cannabinoid-CB 1 antagonism and cholinesterase inhibition, to pharmaceutical compositions comprising these compounds, to methods for preparing these compounds, methods for preparing novel intermediates useful for the synthesis of these compounds, and methods for preparing compositions comprising these compounds. The invention also relates to methods of treating Alzheimer's disease, cognitive disorders, memory disorders, dementia, attention deficit disorder, traumatic brain injury, drug dependence, addiction or substance abuse by administering a pharmaceutical composition comprising these compounds to a patient in need thereof. A compound with a combination of cannabinoid-CB 1 antagonism and cholinesterase inhibition is a compound of formula (1) wherein the symbols have the meanings given in the specification.

  本发明实施例涉及具有大麻素-CB1拮抗和胆碱酯酶抑制作用的化合物，包括这些化合物的制药组合物，制备这些化合物的方法，制备用于合成这些化合物的新型中间体的方法，以及制备包含这些化合物的组合物的方法。本发明还涉及通过向需要此类治疗的患者投与包含这些化合物的制药组合物来治疗阿尔茨海默病、认知障碍、记忆障碍、痴呆、注意力缺陷障碍、创伤性脑损伤、药物依赖、成瘾或药物滥用的方法。具有大麻素-CB1拮抗和胆碱酯酶抑制作用的化合物是式（1）中符号具有规范中给出的含义的化合物。
• COMPOUNDS WITH A COMBINATION OF CANNABINOID CB1 ANTAGONISM AND SEROTONIN REUPTAKE INHIBITION
  申请人：Lange Josephus H.M.

  公开号：US20080214559A1

  公开（公告）日：2008-09-04

  Compounds with a combination of cannabinoid CB 1 antagonism and serotonin re-uptake inhibition, pharmaceutical compositions containing these compounds, methods for preparing these compounds, methods for preparing novel intermediates useful for their synthesis, and methods for preparing these compositions are disclosed. Uses of such compounds and compositions, particularly their use in administering them to patients to achieve a therapeutic effect in psychosis, anxiety, depression, attention deficits, cognitive disorders, obesity, drug dependence, Parkinson's disease, Alzheimer's disease, pain disorders, neuropathic pain disorders and sexual disorders are disclosed. In at least one embodiment, the invention relates to compounds of the general formula (1); wherein the substitutents have the definitions given in the specification.

  本发明涉及一种具有大麻素CB1拮抗和血清素再摄取抑制的化合物组合，含有这些化合物的制药组合物，制备这些化合物的方法，制备用于其合成的新型中间体的方法，以及制备这些组合物的方法。本发明还涉及这些化合物和组合物的用途，特别是将它们用于给患者施用，以在精神病、焦虑、抑郁、注意力缺陷、认知障碍、肥胖症、药物依赖、帕金森病、阿尔茨海默病、疼痛障碍、神经痛障碍和性障碍中实现治疗效果。在至少一个实施例中，本发明涉及一般式（1）的化合物；其中取代基具有规范中给出的定义。
• Formulations and methods for treating acute cannabinoid overdose
  申请人：Anebulo Pharmaceuticals, Inc.

  公开号：US11141404B1

  公开（公告）日：2021-10-12

  Described herein are uses of the CB1 inhibitors (e.g., antagonists, neutral antagonists, inverse agonists) and various methods of using and administering a CB1 inhibitor to a patient, especially patients showing symptoms of drug overdose or suspected of a drug overdose. Further described herein are uses wherein the CB1 inhibitor is ANEB-001. Further described herein are treatments with a CB1 inhibitor for THC or synthetic cannabinoid overdose.

  本文描述了CB1抑制剂（如拮抗剂、中性拮抗剂、逆激动剂）的用途，以及向患者，特别是出现药物过量症状或疑似药物过量的患者使用和施用CB1抑制剂的各种方法。本文进一步描述了CB1抑制剂为ANEB-001的用途。本文还描述了使用 CB1 抑制剂治疗四氢大麻酚或合成大麻素过量的方法。
• AZETIDINECARBOXAMIDE DERIVATIVES AND THEIR USE IN THE TREATMENT OF CB1 RECEPTOR MEDIATED DISORDERS
  申请人：VERNALIS RESEARCH LIMITED

  公开号：EP1620395A1

  公开（公告）日：2006-02-01
• FORMULATIONS AND METHODS FOR TREATING ACUTE CANNABINOID OVERDOSE
  申请人：Anebulo Pharmaceuticals, Inc.

  公开号：US20220151990A1

  公开（公告）日：2022-05-19

  Described herein are uses of the CB1 inhibitors (e.g., antagonists, neutral antagonists, inverse agonists) and various methods of using and administering a CB1 inhibitor to a patient, especially patients showing symptoms of drug overdose or suspected of a drug overdose. Further described herein are uses wherein the CB1 inhibitor is ANEB-001. Further described herein are treatments with a CB1 inhibitor for THC or synthetic cannabinoid overdose.