N-[7-(1,2,3,4-tetrahydroacridin-9-ylamino)heptyl]-2-(2-chlorophenyl)-1-(4-chlorophenyl)-5-ethyl-1H-imidazole-4-carboxamide | 1034783-27-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N-[7-(1,2,3,4-tetrahydroacridin-9-ylamino)heptyl]-2-(2-chlorophenyl)-1-(4-chlorophenyl)-5-ethyl-1H-imidazole-4-carboxamide
• 英文别名: 2-(2-chlorophenyl)-1-(4-chlorophenyl)-5-ethyl-N-[7-(1,2,3,4-tetrahydroacridin-9-ylamino)heptyl]imidazole-4-carboxamide
• CAS: 1034783-27-1
• 化学式: C₃₈H₄₁Cl₂N₅O
• 分子量: 654.682
• InChiKey: IBNHPFJFQUFNTI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.2
• 重原子数：
  46
• 可旋转键数：
  13
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  71.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  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

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。
• US8063062B2
  申请人：——

  公开号：US8063062B2

  公开（公告）日：2011-11-22
• [EN] COMPOUNDS WITH A COMBINATION OF CANNABINOID-CB1 ANTAGONISM AND ACETYLCHOLINESTERASE INHIBITION<br/>[FR] COMPOSÉS PRÉSENTANT UNE COMBINAISON D'ANTAGONISME DE CANABINOÏDE-CB1 ET D'INHIBITION D'ACÉTYLCHOLINESTÉRASE
  申请人：SOLVAY PHARM BV

  公开号：WO2008074816A1

  公开（公告）日：2008-06-26

  [EN] Thisinvention concerns compounds with a combination of cannabinoid-CB₁antagonism and cholinesterase inhibition, to pharmaceutical compositions containing these compounds, to methods for preparing the compounds, methods for preparing novel intermediates useful for their synthesis, and methods for preparing compositions. The invention also relates to the uses of such compounds and compositions, particularly for treating Alzheimer's disease, cognitive disorders, memory disorders, dementia, attention deficits, traumatic brain injury, drug dependence, addiction and substance abuse. In particular the invention relates to compounds of the general Formula (1) wherein the symbols have the meanings given in the specification.
  [FR] Cette invention concerne des composés présentant une combinaison d'antagonisme de canabinoïde-CB₁ et d'inhibition de cholinestérase, des compositions pharmaceutiques contenant ces composés, des procédés pour préparer les procédés, des composés pour préparer de nouveaux intermédiaires utiles pour leur synthèse, et des procédés pour préparer les compositions. L'invention porte également sur les utilisations de tels composés et de telles compositions, en particulier pour traiter la maladie d'Alzheimer, des troubles cognitifs, des troubles de la mémoire, la démence, les déficits de l'attention, une lésion cérébrale traumatique, une dépendance aux drogues, la toxicomanie et l'usage de substances toxiques. En particulier, l'invention porte sur des composés représentés par la Formule générale (1) dans laquelle les symboles ont les significations données dans la description.
• Design, Synthesis, Biological Properties, and Molecular Modeling Investigations of Novel Tacrine Derivatives with a Combination of Acetylcholinesterase Inhibition and Cannabinoid CB₁ Receptor Antagonism
  作者：Jos H. M. Lange、Hein K. A. C. Coolen、Martina A. W. van der Neut、Alice J. M. Borst、Bob Stork、Peter C. Verveer、Chris G. Kruse

  DOI：10.1021/jm901614b

  日期：2010.2.11

  Pyrazolines 7-10 were designed as novel CB1 receptor antagonists, which exhibited improved turbidimetric aqueous solubilities. On the basis of their extended CB1 antagonist pharmacophore, hybrid molecules exhibiting cannabinoid CB1 receptor antagonistic as well as acetylcholinesterase (AChE) inhibiting activities were designed. The target compounds 12, 13, 20, and 21 are based on 1 (tacrine) as the AChE inhibitor (AChEI) pharmacophore and two different CB1 antagonistic pharmacophores. The imidazole-based 20 showed high CB1 receptor affinity (48 nM) in combination with high CB1/CB2 receptor subtype selectivity (> 20-fold) and elicited equipotent AChE inhibitory activity as 1. Molecular modeling studies revealed the presence of a binding pocket in the AChE enzyme which nicely accommodates the CB1 pharmacophores of the target compounds 12, 13, 20, and 21.