5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazole-3-carboxylic acid ethyl ester | 288104-74-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazole-3-carboxylic acid ethyl ester
• 英文别名: 5-(4-bromo-phenyl)-1-(2,4-dichloro-phenyl)-4-ethyl-1H-pyrazole-3-carboxylic acid ethyl ester；ethyl 5-(4-Bromophenyl)-1-(2,4-dichlorophenyl)-4-ethylpyrazole-3-carboxylate
• CAS: 288104-74-5
• 化学式: C₂₀H₁₇BrCl₂N₂O₂
• 分子量: 468.177
• InChiKey: POSRVYDHDWFTRL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 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：

  5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazole-3-carboxylic acid ethyl ester 以97的产率得到5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazole-3-carboxylic acid
  参考文献：
  名称：

  [EN] PYRAZOLECARBOXYLIC ACID DERIVATIVES, THEIR PREPARATION, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
  [FR] DERIVES D'ACIDE PYRAZOLECARBOXYLIQUE, LEUR PREPARATION, LES COMPOSITIONS PHARMACEUTIQUES EN CONTENANT

  摘要：

  Le N-pipéridino-5-(4-bromophényl)-1-(2,4-dichlorophényl)-4-éthylpyrazole-3-carboxamide, ainsi que ses sels et solvants, sont des antagonistes puissants des récepteurs cannabinoïdes CB1. Ils sont préparés en faisant réagir un dérivé fonctionnel de l'acide 5-(4-bromophényl)-1-(2,4-dichlorophényl)-4-éthylpyrazole-3-carboxylique avec de la 1-aminopipéridine, suivie éventuellement d'une salification.

  公开号：

  WO2000046209A1
• 作为产物：
  描述：

  ethyl 3-(4-bromobenzoyl)-2-[(2,4-dichlorophenyl)hydrazono]-pentanoate 在 溶剂黄146 作用下， 反应 24.0h， 以1.35 g的产率得到5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazole-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Discovery of 2-[5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4-ethyl-1H-pyrazol-3-yl]-1,5,5-trimethyl-1,5-dihydro-imidazol-4-thione (BPR-890) via an Active Metabolite. A Novel, Potent and Selective Cannabinoid-1 Receptor Inverse Agonist with High Antiobesity Efficacy in DIO Mice

  摘要：

  By using the active metabolite 5 as an initial template, further structural modifications led to the identification of the titled compound 24 (BPR-890) as a highly potent CB I inverse agonist possessing an excellent CB2/1 selectivity and remarkable in vivo efficacy in diet-induced obese mice with a minimum effective dose as low as 0.03 mg/kg (po qd) at the end of the 30-day chronic study. Current SAR studies along with those of many existing rimonabant-mimicking molecules imply that around the pyrazole C3-position, a rigid and deep binding pocket should exist for CB1 receptor. In addition, relative to the conventional carboxamide carbonyl, serving as a key hydrogen-bond acceptor during ligand-CB1 receptor interaction, the corresponding polarizable thione carbonyl might play a more critical role in stabilizing the Asp366-Lys192 salt bridge in the proposed CB1-receptor homology model and inducing significant selectivity for CB1R over CB2R.

  DOI：

  10.1021/jm900471u

文献信息

• Imidazol-4-one and Imidazole-4-thione Compounds
  申请人：Shia Kak-Shan

  公开号：US20100113546A1

  公开（公告）日：2010-05-06

  Imidazol-4-one or imidazole-4-thione compounds of formula (I): wherein X, R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are defined herein. Also disclosed is a method for treating a cannabinoid receptor-mediated disorder with these compounds.

  咪唑-4-酮或咪唑-4-硫酮化合物的化学式（I）：其中X，R1，R2，R3，R4，R5和R6在此定义。还揭示了使用这些化合物治疗大麻素受体介导的疾病的方法。
• 吡唑甲酸类衍生物、其制备方法和含有它们的药物组合物
  申请人：赛诺菲-安万特

  公开号：CN1146544C

  公开（公告）日：2004-04-21

  本发明涉及是大麻素CB 1 受体强效拮抗剂的N-哌啶子基-5-(4-溴苯基)-1-(2，4-二氯苯基)-4-乙基吡唑-3-甲酰胺、其盐和溶剂化物。其制备方法包括令5-(4-溴苯基)-1-(2，4-二氯苯基)-4-乙基吡唑-3-甲酸的官能衍生物与1-氨基哌啶反应、随后选择性地成盐。
• Pyrazolecarboxylic acid derivatives, their preparation, pharmaceutical compositions containing them
  申请人：Sanofi-Synthelabo

  公开号：US06432984B1

  公开（公告）日：2002-08-13

  N-Piperidino-5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethylpyrazole-3-carboxamide and its salts and solvates are powerful antagonists of the CB1 cannabinoid receptors. They are prepared by reacting a functional derivative of 5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethylpyrazole-3-carboxylic acid with 1-aminopiperidine, optionally followed by salification.

  N-哌啶基-5-(4-溴苯基)-1-(2,4-二氯苯基)-4-乙基吡唑-3-羧酰胺及其盐和溶剂化合物是CB1大麻素受体的强效拮抗剂。它们是通过将5-(4-溴苯基)-1-(2,4-二氯苯基)-4-乙基吡唑-3-羧酸的官能衍生物与1-氨基哌啶反应制备的，可选择性地进行盐化反应。
• Pyrazolecarboxylic acid derivatives, their preparation and pharmaceutical compositions containing them
  申请人：——

  公开号：US20020188007A1

  公开（公告）日：2002-12-12

  N-Piperidino-5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethylpyrazole-3-carboxamide and its salts and solvates are powerful antagonists of the CB 1 cannabinoid receptors. They are prepared by reacting a functional derivative of 5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethylpyrazole-3-carboxylic acid with 1-aminopiperidine, optionally followed by salification.

  N-哌啶基-5-(4-溴苯基)-1-(2,4-二氯苯基)-4-乙基吡唑-3-甲酰胺及其盐类和溶剂是 CB 1 大麻素受体的强效拮抗剂。其制备方法是将 5-(4-溴苯基)-1-(2,4-二氯苯基)-4-乙基吡唑-3-羧酸的功能衍生物与 1-氨基哌啶反应，然后进行盐析。
• Novel pyrazole-3-carboxamide derivatives as cannabinoid-1 (CB1) antagonists: Journey from non-polar to polar amides
  作者：Pradip K. Sasmal、D. Srinivasa Reddy、Rashmi Talwar、B. Venkatesham、D. Balasubrahmanyam、M. Kannan、P. Srinivas、K. Shiva Kumar、B. Neelima Devi、Vikram P. Jadhav、Sanjoy K. Khan、Priya Mohan、Hira Chaudhury、Debnath Bhuniya、Javed Iqbal、Ranjan Chakrabarti

  DOI：10.1016/j.bmcl.2010.10.055

  日期：2011.1

  The synthesis and biological evaluation of novel pyrazole-3-carboxamide derivatives as CB1 antagonists are described. As a part of eastern amide SAR, various chemically diverse motifs were introduced. In general, a range of modifications were well tolerated. Several molecules with high polar surface area were also indentified as potent CB1 receptor antagonists. The in vivo proof of principle for weight loss is exemplified with a lead compound from this series. (C) 2010 Elsevier Ltd. All rights reserved.