1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-methyl-1H-imidazole-4-carboxylic acid | 796875-26-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-methyl-1H-imidazole-4-carboxylic acid
• 英文别名: 1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-methylimidazole-4-carboxylic acid
• CAS: 796875-26-8
• 化学式: C₁₇H₁₁Cl₃N₂O₂
• 分子量: 381.646
• InChiKey: IAYPXDWWSHCJTP-UHFFFAOYSA-N

物化性质

• 熔点：
  243-245 °C
• 沸点：
  588.2±60.0 °C(Predicted)
• 密度：
  1.48±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 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：

  1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-methyl-1H-imidazole-4-carboxylic acid 在 氯化亚砜 作用下， 以 甲苯 为溶剂， 反应 3.0h， 生成 1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-methyl-1H-imidazole-4-carboxyl chloride
  参考文献：
  名称：

  Azole Derivatives as Cannabinoid CB1 Receptor Antagonists

  摘要：

  化合物(I)的新颖唑类化合物或其药用盐作为大麻素CB1受体的反向激动剂或拮抗剂具有良好效果，可用于预防或治疗肥胖和与肥胖相关的代谢紊乱。预防还提供了一种制备该化合物的方法，含有该化合物的药物组合物，以及预防或治疗肥胖和与肥胖相关的代谢紊乱的方法。

  公开号：

  US20080262066A1
• 作为产物：
  描述：

  2,4-dichloro-N-(4-chlorophenyl)benzenecarboximidamide 在 lithium hydroxide 、 碳酸氢钠 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 37.0h， 生成 1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-methyl-1H-imidazole-4-carboxylic acid
  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

• HETEROARYL-IMIDAZOLE DERIVATIVES AS CANNABINOID CB1 RECEPTOR ANTAGONISTS
  申请人：Lee Jinhwa

  公开号：US20080207704A1

  公开（公告）日：2008-08-28

  A heteroaryl-imidazole compound of formula (I) or a pharmaceutically acceptable salt thereof is effective as a cannabinoid CB 1 receptor inverse agonist or antagonist, which is useful for preventing or treating obesity and obesity-related metabolic disorders. The present invention also provides a method for preparing a heteroaryl-imidazole compound of formula (I), a pharmaceutical composition containing a heteroaryl-imidazole compound of formula (I), and a method for preventing or treating obesity and obesity-related metabolic disorders.

  一种具有化学式(I)的杂环芳基咪唑化合物或其药学上可接受的盐作为一种大麻素CB1受体的反向激动剂或拮抗剂，可用于预防或治疗肥胖和与肥胖相关的代谢紊乱。本发明还提供了一种制备具有化学式(I)的杂环芳基咪唑化合物的方法，含有具有化学式(I)的杂环芳基咪唑化合物的药物组合物，以及预防或治疗肥胖和与肥胖相关的代谢紊乱的方法。
• Heteroaryl-Imidazole Derivatives as Cannabinoid CB1 Receptor Antagonists
  申请人：LEE Jinhwa

  公开号：US20080207705A1

  公开（公告）日：2008-08-28

  A novel heteroaryl-imidazole compound of formula (I) or a pharmaceutically acceptable salt thereof is effective as a cannabinoid CB 1 receptor inverse agonist or antagonist, which is useful for preventing or treating obesity and obesity-related metabolic disorders. The present invention also provides a method for preparing same, a pharmaceutical composition containing same, and a method for preventing or treating obesity and obesity-related metabolic disorders.

  一种新型杂环取代咪唑化合物（I）或其药学上可接受的盐，作为大麻素CB1受体的反向激动剂或拮抗剂具有良好的效果，可用于预防或治疗肥胖和肥胖相关的代谢性疾病。本发明还提供了一种制备该化合物的方法，一种含有该化合物的制药组合物以及一种预防或治疗肥胖和肥胖相关代谢性疾病的方法。
• Structure–activity relationship studies of novel pyrazole and imidazole carboxamides as cannabinoid-1 (CB1) antagonists
  作者：Pradip K. Sasmal、Rashmi Talwar、J. Swetha、D. Balasubrahmanyam、B. Venkatesham、Khaji Abdul Rawoof、B. Neelima Devi、Vikram P. Jadhav、Sanjoy K. Khan、Priya Mohan、D. Srinivasa Reddy、Vijay Kumar Nyavanandi、Srinivas Nanduri、K. Shiva Kumar、M. Kannan、P. Srinivas、Prabhakar Nadipalli、Hira Chaudhury、V.J. Sebastian

  DOI：10.1016/j.bmcl.2011.06.017

  日期：2011.8

  The synthesis and biological evaluation of novel pyrazole and imidazole carboxamides as CB1 antagonists are described. As a part of eastern amide SAR, various chemically diverse motifs were introduced on rimonabant template. The central pyrazole core was also replaced with its conformationally constrained motif and imidazole moieties. In general, a range of modifications were well tolerated. Several molecules with low- and sub-nanomolar potencies were identified as potent CB1 receptor antagonists. The in vivo proof of principle for weight loss is demonstrated with a lead compound in DIO mice model. (C) 2011 Elsevier Ltd. All rights reserved.
• Diarylimidazolyl oxadiazole and thiadiazole derivatives as cannabinoid CB1 receptor antagonists
  作者：Jong Yup Kim、Hee Jeong Seo、Sung-Han Lee、Myung Eun Jung、Kwangwoo Ahn、Jeongmin Kim、Jinhwa Lee

  DOI：10.1016/j.bmcl.2008.10.130

  日期：2009.1

  Since the CB1 receptor antagonist SR141716 (rimonabant) was reported to modulate food intake, CB1 antagonism has been considered as a new therapeutic target in the treatment of obesity. Several series of derivatives based on diarylimidazolyl oxadiazole and thiadiazole scaffolds were synthesized and tested for CB1 receptor binding affinity. SAR studies directed toward the optimization of imidazole scaffolds resulted in the discovery of 10s which showed highest potency for CB1 receptor binding affinity (IC50 = 1.91 nM) prepared to date. (C) 2008 Elsevier Ltd. All rights reserved.
• USE OF CBX CANNABINOID RECEPTOR MODULATORS AS POTASSIUM CHANNEL MODULATORS
  申请人：Solvay Pharmaceuticals GmbH

  公开号：EP2012775A1

  公开（公告）日：2009-01-14