1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-1H-pyrazole-3-carboxylic acid ethyl ester | 501426-53-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-1H-pyrazole-3-carboxylic acid ethyl ester
• 英文别名: 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-1H-pyrazole-3-carboxylic acid ethyl ester；ethyl 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-1H-pyrazole-3-carboxylate；5-(4-chloro-phenyl)-1-(2,4-dichloro-phenyl)-1H-pyrazole-3-carboxylic acid ethyl ester；ethyl 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)pyrazole-3-carboxylate
• CAS: 501426-53-5
• 化学式: C₁₈H₁₃Cl₃N₂O₂
• 分子量: 395.672
• InChiKey: OOPJBSBXXQYOIR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 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：

  1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-1H-pyrazole-3-carboxylic acid ethyl ester 在 水 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 3.0h， 以95%的产率得到1-(2,4-二氯苯基)-5-(4-氯苯基)-1H-吡唑-3-羧酸
  参考文献：
  名称：

  [EN] SUBSTITUTED PYRAZOLE COMPOUNDS AS CB1 RECEPTOR ANTAGONISTS AND USES THEREOF
  [FR] COMPOSÉS PYRAZOLE SUBSTITUÉS COMME ANTAGONISTES DU RÉCEPTEUR CB1 ET LEURS UTILISATIONS

  摘要：

  本发明涉及公式1的化合物，或其同位素形式、立体异构体、互变异构体、药学上可接受的盐、溶剂合物、多型体、前药、S-氧化物或N-氧化物，以及它们的制备方法。该发明还涉及含有这些化合物的药物组合物；以及公式1的化合物和含有这些化合物的药物组合物在治疗由大麻素1（CB1）受体介导的疾病或障碍中的用途。

  公开号：

  WO2015162452A1
• 作为产物：
  描述：

  在 溶剂黄146 作用下， 反应 24.0h， 以1.73 g的产率得到1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-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

• Heteroaryl-Pyrazole Derivatives as Cannabinoid CB1 Receptor Antagonists
  申请人：LEE Jinhwa

  公开号：US20080081812A1

  公开（公告）日：2008-04-03

  A heteroaryl-pyrazole 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 the inventive heteroaryl-pyrasole compounds or a pharmaceutically acceptable salt thereof, a pharmaceutical composition containing same, and a method for preventing or treating obesity and obesity-related metabolic disorders.

  一种异芳基-吡唑化合物，其公式为(I)或其药用可接受盐，可作为大麻素CB1受体的反向激动剂或拮抗剂，用于预防或治疗肥胖及其相关代谢紊乱。本发明还提供了制备本发明的异芳基-吡唑化合物或其药用可接受盐的方法，包含该化合物的药物组合物，以及用于预防或治疗肥胖及其相关代谢紊乱的方法。
• 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。
• [EN] SUBSTITUTED PYRAZOLE COMPOUNDS AS CB1 RECEPTOR ANTAGONISTS AND USES THEREOF<br/>[FR] COMPOSÉS PYRAZOLE SUBSTITUÉS COMME ANTAGONISTES DU RÉCEPTEUR CB1 ET LEURS UTILISATIONS
  申请人：PIRAMAL ENTPR LTD

  公开号：WO2015162452A1

  公开（公告）日：2015-10-29

  The present invention relates to compounds of formula 1, or isotopic forms, stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, polymorphs, prodrugs, S-oxides or N-oxides thereof, and processes for their preparation. The invention further relates to pharmaceutical compositions containing the compounds; and use of the compounds of formula 1 and the pharmaceutical compositions comprising the compounds in the treatment of diseases or disorders mediated by cannabinoid 1 (CB1) receptors.

  本发明涉及公式1的化合物，或其同位素形式、立体异构体、互变异构体、药学上可接受的盐、溶剂合物、多型体、前药、S-氧化物或N-氧化物，以及它们的制备方法。该发明还涉及含有这些化合物的药物组合物；以及公式1的化合物和含有这些化合物的药物组合物在治疗由大麻素1（CB1）受体介导的疾病或障碍中的用途。
• PYRAZOLE COMPOUNDS
  申请人：Shia Kak-Shan

  公开号：US20080090809A1

  公开（公告）日：2008-04-17

  This invention relates to pyrazole compounds of formula (I) shown below: Each variable in formula (I) is defined in the specification. These compounds can be used to treat cannabinoid-receptor mediated disorders.

  这项发明涉及下面所示的式(I)的吡唑化合物：式(I)中的每个变量在说明书中有定义。这些化合物可用于治疗大麻素受体介导的疾病。
• Antiobesity designed multiple ligands: Synthesis of pyrazole fatty acid amides and evaluation as hypophagic agents
  作者：Mario Alvarado、Pilar Goya、Manuel Macías-González、Francisco Javier Pavón、Antonia Serrano、Nadine Jagerovic、Jose Elguero、Angel Gutiérrez-Rodríguez、Santiago García-Granda、Margarita Suardíaz、Fernando Rodríguez de Fonseca

  DOI：10.1016/j.bmc.2008.10.023

  日期：2008.12

  Searching for new antiobesity agents, a new series of fatty acid amide derivatives of 1,5-diarylpyrazole have been synthesized as dual peroxisome proliferator activated receptor alpha (PPARalpha)/cannabinoid receptor ligands. The compounds have been evaluated in vivo and in vitro as PPARalpha activators and as cannabinoids in two tests of the mouse tetrad. In vivo, food intake studies have been performed

  为了寻找新的减肥药，已经合成了一系列新的1,5-二芳基吡唑脂肪酸酰胺衍生物，作为双重过氧化物酶体增殖物激活受体α（PPARalpha）/大麻素受体配体。在小鼠四联体的两次测试中，已将这些化合物作为PPARalpha激活剂和大麻素在体内和体外进行了评估。在体内，已经对所有化合物进行了食物摄入研究。没有发现明显的大麻素活性，但是一些化合物具有有效的PPARalpha活化剂的作用。几种化合物显示出厌食特性，从而减少了大鼠的食物摄入。