1-(2,4-dichlorophenyl)-4-bromo-5-(4-chlorophenyl)-1H-pyrazole-3-carboxylic acid ethyl ester | 501426-57-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(2,4-dichlorophenyl)-4-bromo-5-(4-chlorophenyl)-1H-pyrazole-3-carboxylic acid ethyl ester
• 英文别名: 4-bromo-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-1H-pyrazole-3-carboxylic acid ethyl ester；ethyl 4-bromo-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-1H-pyrazole-3-carboxylate；ethyl 4-bromo-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)pyrazole-3-carboxylate
• CAS: 501426-57-9
• 化学式: C₁₈H₁₂BrCl₃N₂O₂
• 分子量: 474.568
• InChiKey: GSIWZGJMHDMIHM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  26
• 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)-4-bromo-5-(4-chlorophenyl)-1H-pyrazole-3-carboxylic acid ethyl ester 在 氢氧化钾 、 氯化亚砜 作用下， 以 甲醇 、 甲苯 为溶剂， 生成
  参考文献：
  名称：

  Synthesis, Structure−Activity Relationship, and Evaluation of SR141716 Analogues:  Development of Central Cannabinoid Receptor Ligands with Lower Lipophilicity

  摘要：

  Exploration of the central CB1 cannabinoid receptors using positron emission tomography (PET) will allow for an understanding of the pharmacological and physiological role played by these receptors in the CNS. Current tracers are highly lipophilic compounds that exhibit very high nonspecific to specific binding ratios and as a result are inapt for use in humans. We have synthesized a series of less lipophilic analogues of SR141716 to serve as potential radioligands. Binding affinities of the series and a functional electrophysiological assay of three of our compounds have been presented.

  DOI：

  10.1021/jm020157x
• 作为产物：
  描述：

  2,4-二氯苯肼盐酸盐 在 溴 、 lithium hexamethyldisilazane 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 生成 1-(2,4-dichlorophenyl)-4-bromo-5-(4-chlorophenyl)-1H-pyrazole-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Synthesis, Structure−Activity Relationship, and Evaluation of SR141716 Analogues:  Development of Central Cannabinoid Receptor Ligands with Lower Lipophilicity

  摘要：

  Exploration of the central CB1 cannabinoid receptors using positron emission tomography (PET) will allow for an understanding of the pharmacological and physiological role played by these receptors in the CNS. Current tracers are highly lipophilic compounds that exhibit very high nonspecific to specific binding ratios and as a result are inapt for use in humans. We have synthesized a series of less lipophilic analogues of SR141716 to serve as potential radioligands. Binding affinities of the series and a functional electrophysiological assay of three of our compounds have been presented.

  DOI：

  10.1021/jm020157x

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。
• Heteroaryl-pyrazole derivatives as cannabinoid CB1 receptor antagonists
  申请人：Green Cross Corporation

  公开号：US07875647B2

  公开（公告）日：2011-01-25

  A heteroaryl-pyrazole compound of formula (I) or a pharmaceutically acceptable salt thereof is effective as a cannabinoid CB1 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.

  式(I)的杂环吡唑化合物或其药学上可接受的盐，是一种有效的大麻素CB1受体反向激动剂或拮抗剂，可用于预防或治疗肥胖和肥胖相关代谢障碍。本发明还提供了一种制备上述杂环吡唑化合物或其药学上可接受的盐的方法，以及包含它们的制药组合物和预防或治疗肥胖和肥胖相关代谢障碍的方法。
• Biarylpyrazolyl Oxadiazole as Potent, Selective, Orally Bioavailable Cannabinoid-1 Receptor Antagonists for the Treatment of Obesity
  作者：Suk Ho Lee、Hee Jeong Seo、Sung-Han Lee、Myung Eun Jung、Ji-Hyun Park、Hyun-Ju Park、Jakyung Yoo、Hoseop Yun、Jooran Na、Suk Youn Kang、Kwang-Seop Song、Min-ah Kim、Chong-Hwan Chang、Jeongmin Kim、Jinhwa Lee

  DOI：10.1021/jm800843r

  日期：2008.11.27

  Since the CB1 cannabinoid receptor antagonist 1 (SR141716, rimonabant) was previously reported to modulate food intake, CB1 antagonism has been considered as a new therapeutic target for the treatment of obesity. In the present study, biarylpyrazole analogues based on a pyrazole core coupled with 1,3,4-oxadiazole were synthesized and tested for CB1 receptor binding affinity. Thorough SAR studies to optimize pyrazole substituents as well as 1,3,4-oxadiazole ring led to several novel CB1 antagonists with IC50 similar to 1 nM for the CB1 receptor binding. Among these analogues, we identified 2-(4-((1H-1,2,4-triazol-1-yl)methyl)-5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-1H-pyrazol-3-yl)-5-(1-(trifluoromethyl)cyclopropyl)-1,3,4-oxa- diazole 43c as a promising precandidate for the development as an antiobesity agent.
• Discovery of 2-[5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4-ethyl-1<i>H</i>-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
  作者：Chien-Huang Wu、Ming-Shiu Hung、Jen-Shin Song、Teng-Kuang Yeh、Ming-Chen Chou、Cheng-Ming Chu、Jiing-Jyh Jan、Min-Tsang Hsieh、Shi-Liang Tseng、Chun-Ping Chang、Wan-Ping Hsieh、Yinchiu Lin、Yen-Nan Yeh、Wan-Ling Chung、Chun-Wei Kuo、Chin-Yu Lin、Horng-Shing Shy、Yu-Sheng Chao、Kak-Shan Shia

  DOI：10.1021/jm900471u

  日期：2009.7.23

  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.
• HETEROARYL-PYRAZOLE DERIVATIVES AS CANNABINOID CB1 RECEPTOR ANTAGONISTS
  申请人：Green Cross Corporation

  公开号：EP2097410A1

  公开（公告）日：2009-09-09