ethyl 2-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-1H-imidazole-4-carboxylate | 505073-36-9

• 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 2-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-1H-imidazole-4-carboxylate
• 英文别名: 2-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-1H-imidazole-4-carboxylic acid ethyl ester；ethyl 2-(4-chlorophenyl)-1-(2,4-dichlorophenyl)imidazole-4-carboxylate
• CAS: 505073-36-9
• 化学式: C₁₈H₁₃Cl₃N₂O₂
• 分子量: 395.672
• InChiKey: QHFZEXZBGBLPFZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 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 2-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-1H-imidazole-4-carboxylate 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 1.5h， 以85%的产率得到2-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-1H-imidazole-4-carboxylic acid
  参考文献：
  名称：

  Synthesis, Structure−Activity Relationships at the GABA_A Receptor in Rat Brain, and Differential Electrophysiological Profile at the Recombinant Human GABA_A Receptor of a Series of Substituted 1,2-Diphenylimidazoles

  摘要：

  A series of new 1,2-diphenylimidazole derivatives (la-x) were synthesized and evaluated for their ability to potentiate gamma-aminobutyric acid (GABA)-evoked currents in Xenopus laevis oocytes expressing recombinant human GABAA receptors. Many of these compounds enhanced GABA action with potencies (EC50 = 0.19-19,mu M) and efficacies (maximal efficacies of up to 640%) similar to or greater than those of anesthetics such as etomidate, propofol, and alphaxalone. Structure- activity relationship analysis revealed that the presence of an ester moiety in the imidazole ring was required for full agonist properties, while modifications made in the phenyl rings affected potency and efficacy, with ethyl 2-(4-bromophenyl)-l-(2,4-dichlorophenyl)-1H4-imidazolecarboxylate showing the highest potency. These compounds potentiated the [H-3]GABA binding to rat brain membranes, suggesting a site of interaction different from that of GABA. As for etomidate, mutation of asparagine-265 in the beta 2 subunit of the GABA(A) receptor into serine reduced the ability of derivative 1i to modulate the GABA function.

  DOI：

  10.1021/jm049120y
• 作为产物：
  描述：

  2,4-二氯苯胺 在 三甲基铝 、 碳酸氢钠 、 对甲苯磺酸 作用下， 以 异丙醇 、 甲苯 为溶剂， 生成 ethyl 2-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-1H-imidazole-4-carboxylate
  参考文献：
  名称：

  Synthesis, Structure−Activity Relationships at the GABA_A Receptor in Rat Brain, and Differential Electrophysiological Profile at the Recombinant Human GABA_A Receptor of a Series of Substituted 1,2-Diphenylimidazoles

  摘要：

  A series of new 1,2-diphenylimidazole derivatives (la-x) were synthesized and evaluated for their ability to potentiate gamma-aminobutyric acid (GABA)-evoked currents in Xenopus laevis oocytes expressing recombinant human GABAA receptors. Many of these compounds enhanced GABA action with potencies (EC50 = 0.19-19,mu M) and efficacies (maximal efficacies of up to 640%) similar to or greater than those of anesthetics such as etomidate, propofol, and alphaxalone. Structure- activity relationship analysis revealed that the presence of an ester moiety in the imidazole ring was required for full agonist properties, while modifications made in the phenyl rings affected potency and efficacy, with ethyl 2-(4-bromophenyl)-l-(2,4-dichlorophenyl)-1H4-imidazolecarboxylate showing the highest potency. These compounds potentiated the [H-3]GABA binding to rat brain membranes, suggesting a site of interaction different from that of GABA. As for etomidate, mutation of asparagine-265 in the beta 2 subunit of the GABA(A) receptor into serine reduced the ability of derivative 1i to modulate the GABA function.

  DOI：

  10.1021/jm049120y

文献信息

• 1 H-imidazole derivatives having CB1 agonistic, CB1 partial agonistic or CB1-antagonistic activity
  申请人：Kruse G. Cornelis

  公开号：US20050054679A1

  公开（公告）日：2005-03-10

  The present invention relates to a group of novel 1H-imidazole derivatives, to methods for the preparation of these compounds, and to pharmaceutical compositions containing one or more of these compounds as an active component. These 1H-imidazole derivatives are potent cannabinoid-CB 1 receptor agonists, partial agonists or antagonists, useful for the treatment of psychiatric and neurological disorders, as well as and other diseases involving cannabinoid neurotransmission. The compounds have the general formula (I) wherein R and R 1 -R 4 have the meanings given in the specification.

  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。
• 1H-imidazole derivatives having cb1 agonistic, cb1 partial agonistic or cb1 antagonistic activity
  申请人：——

  公开号：US20040235854A1

  公开（公告）日：2004-11-25

  The present invention relates to a group of novel 1H-imidazole derivatives, to methods for the preparation of these compounds, and to pharmaceutical compositions containing one or more of these compounds as an active component. These 1H-imidazole derivatives are potent cannabinoid-CB1 receptor agonists, partial agonists or antagonists, useful for the treatment of psychiatric and neurological disorders, as well as and other diseases involving cannabinoid neurotransmission. The compounds have the general formula (I) wherein R and R1-R4 have the meanings given in the specification. 1

  本发明涉及一组新型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，可用于治疗精神和神经系统疾病，以及其他涉及大麻素神经递质的疾病。这些化合物的一般式为(I)，其中R和R1-R4在规范中给出了它们的含义。
• 1H-IMIDAZOLE DERIVATIVE HAVING CB1, AGONISTIC, CB1 PARTIAL AGONISTIC OR CB1 ANTAGNISTIC ACTIVITY
  申请人：KRUSE Cornelis G.

  公开号：US20090181949A1

  公开（公告）日：2009-07-16

  The present invention relates to a group of novel 1H-imidazole derivatives, to methods for the preparation of these compounds, and to pharmaceutical compositions containing one or more of these compounds as an active component. These 1H-imidazole derivatives are potent cannabinoid-CB1 receptor agonists, partial agonists or antagonists, useful for the treatment of psychiatric and neurological disorders, as well as and other diseases involving cannabinoid neurotransmission. The compounds have the general formula (I) wherein R and R1-R4 have the meanings given in the specification.

  本发明涉及一组新型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，可用于治疗精神和神经疾病，以及其他涉及大麻素神经传递的疾病。这些化合物的一般式为(I)，其中R和R1-R4在说明书中有所描述。
• 1H-IMIDAZOLE DERIVATIVES HAVING CB1 AGONISTIC, CB1 PARTIAL AGONISTIC OR CB1- ANTAGONISTIC ACTIVITY
  申请人：Solvay Pharmaceuticals B.V.

  公开号：EP1438296B1

  公开（公告）日：2008-11-26
• US7109216B2
  申请人：——

  公开号：US7109216B2

  公开（公告）日：2006-09-19