2-(2-Chlorophenyl)-1-(4-chlorophenyl)-5-methylimidazole-4-carboxylic acid | 942435-72-5

• 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-methylimidazole-4-carboxylic acid
• CAS: 942435-72-5
• 化学式: C₁₇H₁₂Cl₂N₂O₂
• 分子量: 347.2
• InChiKey: FJWWILDIVOCJLL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  23
• 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：

  2-(2-Chlorophenyl)-1-(4-chlorophenyl)-5-methylimidazole-4-carboxylic acid 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 四氯化碳 、 乙醇 、 二氯甲烷 为溶剂， 反应 1.25h， 生成 {3-(4-chloro-phenyl)-2-(2-chloro-phenyl)-5-[4-(2-fluoro-phenyl)-piperidine-1-carbonyl]-3H-imidazol-4-yl}-acetonitrile
  参考文献：
  名称：

  [EN] CB1 RECEPTOR MODULATORS
  [FR] MODULATEURS DE RÉCEPTEUR CB1

  摘要：

  公开号：

  WO2009153569A3
• 作为产物：
  描述：

  邻氯苯腈 在 sodium hexamethyldisilazane 、 碳酸氢钠 作用下， 以 四氢呋喃 、 异丙醇 为溶剂， 反应 38.0h， 生成 2-(2-Chlorophenyl)-1-(4-chlorophenyl)-5-methylimidazole-4-carboxylic acid
  参考文献：
  名称：

  [EN] CB1 RECEPTOR MODULATORS
  [FR] MODULATEURS DE RÉCEPTEUR CB1

  摘要：

  公开号：

  WO2009153569A3

文献信息

• 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.
• 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.