2-(2-chlorophenyl)-1-(4-chlorophenyl)-5-ethyl-1H-imidazole-4-carboxylic acid | 942435-74-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(2-chlorophenyl)-1-(4-chlorophenyl)-5-ethyl-1H-imidazole-4-carboxylic acid
• 英文别名: 2-(2-chlorophenyl)-1-(4-chlorophenyl)-5-ethylimidazole-4-carboxylic acid
• CAS: 942435-74-7
• 化学式: C₁₈H₁₄Cl₂N₂O₂
• 分子量: 361.227
• InChiKey: KKGOLWWWLBHJRN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(2-chlorophenyl)-1-(4-chlorophenyl)-5-ethyl-1H-imidazole-4-carboxylic acid 、 N-(7-aminoheptyl)-1,2,3,4-tetrahydroacridin-9-amine 在 N-羟基-7-氮杂苯并三氮唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 60.0h， 以53%的产率得到N-[7-(1,2,3,4-tetrahydroacridin-9-ylamino)heptyl]-2-(2-chlorophenyl)-1-(4-chlorophenyl)-5-ethyl-1H-imidazole-4-carboxamide
  参考文献：
  名称：

  COMPOUNDS WITH A COMBINATION OF CANNABINOID-CB1 ANTAGONISM AND ACETYLCHOLINESTERASE INHIBITION

  摘要：

  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。

  公开号：

  US20080153867A1
• 作为产物：
  描述：

  ethyl 2-(2-chlorophenyl)-1-(4-chlorophenyl)-5-ethyl-1H-imidazole-4-carboxylate 在 lithium hydroxide 、 水 、 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 16.0h， 以84%的产率得到2-(2-chlorophenyl)-1-(4-chlorophenyl)-5-ethyl-1H-imidazole-4-carboxylic acid
  参考文献：
  名称：

  COMPOUNDS WITH A COMBINATION OF CANNABINOID-CB1 ANTAGONISM AND ACETYLCHOLINESTERASE INHIBITION

  摘要：

  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。

  公开号：

  US20080153867A1

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。
• Compounds with a combination of cannabinoid-CB1 antagonism and acetylcholinesterase inhibition
  申请人：Solvay Pharmaceuticals B.V.

  公开号：US08063062B2

  公开（公告）日：2011-11-22

  Embodiments of this invention relate to compounds having a combination of cannabinoid-CB1 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-CB1 antagonism and cholinesterase inhibition is a compound of formula (1) wherein the symbols have the meanings given in the specification.

  本发明的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，用于合成这些化合物的新型中间体的制备方法以及制备包括这些化合物的组合物的方法。本发明还涉及通过向需要治疗阿尔茨海默病、认知障碍、记忆障碍、痴呆症、注意力缺陷障碍、创伤性脑损伤、药物依赖、成瘾或药物滥用的患者施用包含这些化合物的制药组合物来治疗这些疾病的方法。具有大麻素-CB1拮抗和胆碱酯酶抑制作用的化合物是式（1）中符号所表示的化合物，其中符号的含义在说明书中给出。
• Compounds with a combination of cannabinoid CB1 antagonism and serotonin reuptake inhibition
  申请人：Solvay Pharmaceuticals B.V.

  公开号：US08138174B2

  公开（公告）日：2012-03-20

  Compounds with a combination of cannabinoid CB1 antagonism and serotonin reuptake 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作用的化合物组合，以及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，特别是它们在治疗精神病、焦虑症、抑郁症、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、神经病性疼痛障碍和性障碍中的应用。在至少一种实施例中，本发明涉及具有一般式（1）中所述取代基的化合物：其中所述取代基的定义在说明书中给出。
• Optimization of imidazole amide derivatives as cannabinoid-1 receptor antagonists for the treatment of obesity
  作者：Roger A. Smith、Zahra Fathi、Furahi Achebe、Christiana Akuche、Su-Ellen Brown、Soongyu Choi、Jianmei Fan、Susan Jenkins、Harold C.E. Kluender、Anish Konkar、Rico Lavoie、Ronald Mays、Jennifer Natoli、Stephen J. O’Connor、Astrid A. Ortiz、Ning Su、Christy Taing、Susan Tomlinson、Theresa Tritto、Gan Wang、Stephan-Nicholas Wirtz、Wai Wong、Xiao-Fan Yang、Shihong Ying、Zhonghua Zhang

  DOI：10.1016/j.bmcl.2007.03.011

  日期：2007.5

  Several imidazole-based cyclohexyl amides were identified as potent CB-1 antagonists, but they exhibited poor oral exposure in rodents. Incorporation of a hydroxyl moiety on the cyclohexyl ring provided a dramatic improvement in oral exposure, together with a ca. 10-fold decrease in potency. Further optimization provided the imidazole 2-hydroxy-cyclohexyl amide 45, which exhibited hCB-1 K-i = 3.7 nM and caused significant appetite suppression and robust, dose-dependent reduction of body weight gain in industry-standard rat models. (c) 2007 Elsevier Ltd. All rights reserved.