ethyl 5-(bromomethyl)-1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-1H-imidazole-4-carboxylate | 796875-43-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 5-(bromomethyl)-1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-1H-imidazole-4-carboxylate
• 英文别名: ethyl 5-bromomethyl-1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-1H-imidazole-4-carboxylate；ethyl 5-(bromomethyl)-1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)imidazole-4-carboxylate
• CAS: 796875-43-9
• 化学式: C₁₉H₁₄BrCl₃N₂O₂
• 分子量: 488.595
• InChiKey: OAXTVEXFMYELKH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 5-(bromomethyl)-1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-1H-imidazole-4-carboxylate 在 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 以63%的产率得到1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-hydroxymethyl-1H-imidazole-4-carboxylic acid
  参考文献：
  名称：

  1 H-imidazole derivatives having CB1 agonistic, CB1 partial agonistic or CB1-antagonistic activity

  摘要：

  本发明涉及一组新颖的1H-咪唑衍生物，以及制备这些化合物的方法和含有这些化合物中的一个或多个作为活性成分的药物组合物。这些1H-咪唑衍生物是有效的大麻素-CB1受体激动剂、部分激动剂或拮抗剂，可用于治疗精神疾病和神经系统疾病，以及其他涉及大麻素神经传递的疾病。这些化合物具有通式（I），其中R和R1-R4的含义如规范中所述。

  公开号：

  US20050054679A1
• 作为产物：
  描述：

  2-丁酮酸乙酯 在 N-溴代丁二酰亚胺(NBS) 、 溴 、 碳酸氢钠 、 过氧化苯甲酰 作用下， 以 四氯化碳 、 乙醇 为溶剂， 反应 59.0h， 生成 ethyl 5-(bromomethyl)-1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-1H-imidazole-4-carboxylate
  参考文献：
  名称：

  利莫那班吡唑部分的生物立体置换：噻唑，三唑和咪唑作为有效和选择性的CB1大麻素受体拮抗剂的合成，生物学性质和分子模型研究。

  摘要：

  基于有效的CB（1）受体拮抗剂利莫那班（SR141716A，1）中存在的1,5-二芳基吡唑基序，将噻唑，三唑和咪唑系列设计为生物等排体。合成了许多目标化合物，并在大麻素（hCB（1）和hCB（2））受体分析中进行了评估。噻唑，三唑和咪唑具有体外（）（）CB（1）拮抗活性，通常表现出相当大的CB（1）与CB（2）受体亚型选择性，从而证明是原始的二芳基吡唑类的大麻素生物等排体。咪唑系列的一些主要代表在CB激动剂诱导的低血压模型和CB激动剂诱导的低体温模型中均显示出口服给药后体内的有效药理活性。分子模型研究表明，关键化合物62和利莫那班之间存在紧密的三维结构重叠。结构-活性关系（SAR）研究表明，咪唑和吡唑系列的生物学结果之间存在密切的相关性。

  DOI：

  10.1021/jm040843r

文献信息

• 1H-imidazole derivatives as cannabinoid receptor modulators
  申请人：Lange H.M. Josephus

  公开号：US20050137197A1

  公开（公告）日：2005-06-23

  The invention relates to a group of 1H-imidazole derivatives which are modulators of cannabinoid receptors, to methods for the preparation of these compounds, to novel intermediates useful for the synthesis of said imidazole derivatives, to methods for the preparation of these intermediates, to pharmaceutical compositions containing one or more of these 1H-imidazole derivatives as active ingredient, as well as to the use of these pharmaceutical compositions for the treatment of psychiatric and neurological disorders in which cannabinoid receptors are involved. The compounds have the general formula (I) wherein R, R 1 -R 4 and X have the meanings given in the specification.

  本发明涉及一类1H-咪唑衍生物，其为大麻素受体调节剂，涉及制备这些化合物的方法，有用于合成所述咪唑衍生物的新型中间体，制备这些中间体的方法，含有一种或多种所述1H-咪唑衍生物作为活性成分的药物组合物，以及使用这些药物组合物治疗牵涉到大麻素受体的精神和神经疾病的方法。所述化合物具有通式（I），其中R、R1-R4和X的含义如规范中所述。
• 1 H-IMIDAZOLE DERIVATIVES AS CANNABINOID RECEPTOR MODULATORS
  申请人：Lange H.M. Josephus

  公开号：US20070281974A1

  公开（公告）日：2007-12-06

  The invention relates to a group of 1H-imidazole derivatives which are modulators of cannabinoid receptors, to methods for the preparation of these compounds, to novel intermediates useful for the synthesis of said imidazole derivatives, to methods for the preparation of these intermediates, to pharmaceutical compositions containing one or more of these 1H-imidazole derivatives as active ingredient, as well as to the use of these pharmaceutical compositions for the treatment of psychiatric and neurological disorders in which cannabinoid receptors are involved. The compounds have the general formula (I) wherein R, R 1 —R 4 and X have the meanings given in the specification.

  本发明涉及一组1H-咪唑衍生物，它们是大麻素受体调节剂，涉及制备这些化合物的方法，有用于合成所述咪唑衍生物的新型中间体，制备这些中间体的方法，含有一种或多种这些1H-咪唑衍生物作为活性成分的药物组合物，以及使用这些药物组合物治疗精神和神经疾病，其中涉及大麻素受体。这些化合物具有通式（I），其中R、R1-R4和X具有规范中给出的含义。
• 1 H-imidazole derivatives as cannabinoid receptor modulators
  申请人：Solvay Pharmaceuticals, Inc.

  公开号：US07498348B2

  公开（公告）日：2009-03-03

  The invention relates to a group of 1H-imidazole derivatives which are modulators of cannabinoid receptors, to methods for the preparation of these compounds, to novel intermediates useful for the synthesis of said imidazole derivatives, to methods for the preparation of these intermediates, to pharmaceutical compositions containing one or more of these 1H-imidazole derivatives as active ingredient, as well as to the use of these pharmaceutical compositions for the treatment of psychiatric and neurological disorders in which cannabinoid receptors are involved. The compounds have the general formula (I) wherein R, R1-R4 and X have the meanings given in the specification.

  本发明涉及一组1H-咪唑衍生物，它们是大麻素受体调节剂，涉及制备这些化合物的方法，有用于合成所述咪唑衍生物的新型中间体，制备这些中间体的方法，含有其中一种或多种1H-咪唑衍生物作为活性成分的制药组合物，以及这些制药组合物在涉及大麻素受体的精神和神经疾病的治疗中的使用。这些化合物具有通式（I），其中R、R1-R4和X的含义如规范中所给出。
• [EN] 1H-IMIDAZOLE DERIVATIVES AS CANNABINOID RECEPTOR MODULATORS<br/>[FR] DERIVES DE 1H-IMIDAZOLE COMME MODULATEURS DE RECEPTEURS CANNABINOIDES
  申请人：SOLVAY PHARM BV

  公开号：WO2005040130A1

  公开（公告）日：2005-05-06

  The invention relates to a group of 1H -imidazole derivatives which are modulators of cannabinoid receptors, to methods for the preparation of these compounds, to novel intermediates useful for the synthesis of said imidazole derivatives, to methods for the preparation of these intermediates, to pharmaceutical compositions containing one or more of these 1H-imidazole derivatives as active ingredient, as well as to the use of these pharmaceutical compositions for the treatment of psychiatric and neurological disorders in which cannabinoid receptors are involved. The compounds have the general formula (I) wherein R, R1-R4 and X have the meanings given in the specification.

  本发明涉及一组1H-咪唑衍生物，它们是大麻素受体调节剂，涉及制备这些化合物的方法，有用于合成所述咪唑衍生物的新型中间体，制备这些中间体的方法，包含一种或多种这些1H-咪唑衍生物作为活性成分的制药组合物，以及利用这些制药组合物治疗涉及大麻素受体的精神和神经疾病的用途。所述化合物具有通式(I)，其中R、R1-R4和X的含义在规范中给出。
• Probing the cannabinoid CB1/CB2 receptor subtype selectivity limits of 1,2-diarylimidazole-4-carboxamides by fine-tuning their 5-substitution pattern
  作者：Jos H.M. Lange、Martina A.W. van der Neut、Alice J.M. Borst、Mahmut Yildirim、Herman H. van Stuivenberg、Bernard J. van Vliet、Chris G. Kruse

  DOI：10.1016/j.bmcl.2010.03.068

  日期：2010.5

  The cannabinoid CB1/CB2 receptor subtype selectivity in the 1,2-diarylimidazole-4-carboxamide series was boosted by fine-tuning its 5-substitution pattern. The presence of the 5-methylsulfonyl group in 11 led to a greater than similar to 840-fold CB1/CB2 subtype selectivity. The compounds 10, 18 and 19 were found more active than rimonabant (1) in a CB1-mediated rodent hypotension model after oral administration. Our findings suggest a limited brain exposure of the P-glycoprotein substrates 11, 12 and 21. (C) 2010 Elsevier Ltd. All rights reserved.