4-((1H-1,2,4-triazol-1-yl)methyl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-1H-pyrazole-3-carbonyl chloride | 1020809-13-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-((1H-1,2,4-triazol-1-yl)methyl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-1H-pyrazole-3-carbonyl chloride
• CAS: 1020809-13-5
• 化学式: C₁₉H₁₁Cl₄N₅O
• 分子量: 467.141
• InChiKey: OOSVDVFKPZUACT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.52
• 重原子数：
  29.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  65.6
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  4-((1H-1,2,4-triazol-1-yl)methyl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-1H-pyrazole-3-carbonyl chloride 、 环己胺 以 二氯甲烷 为溶剂， 反应 1.0h， 以157 mg的产率得到4-((1H-1,2,4-triazol-1-yl)methyl)-5-(4-chlorophenyl)-N-cyclohexyl-1-(2,4-dichlorophenyl)-1H-pyrazole-3-carboxamide
  参考文献：
  名称：

  Synthesis and structure–activity relationship of 1,2,4-triazole-containing diarylpyrazolyl carboxamide as CB1 cannabinoid receptor–ligand

  摘要：

  Numerous research groups have been engaged in searching for novel CB1 receptor antagonists, since SR141716A (rimonabant), a CB1 receptor antagonist, proved to be efficacious in human for the treatment of obesity. In the present study, a series of 1,2,4-triazole-containing diarylpyrazolyl carboxamides based on the 1,5-diarylpyrazole template of rimonabant, was synthesized and tested for CB1 receptor binding affinity. The structure-activity relationship studies demonstrated that incorporation of 1,2,4-triazole ring onto the pyrazole scaffold via a methylene linker led to a significant improvement for CB1 receptor binding affinity. Importantly, these analogues also exhibited excellent selectivity for CB1 receptor over CB2 receptor. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.12.040
• 作为产物：
  描述：

  4-((1H-1,2,4-triazol-1-yl)methyl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-1H-pyrazole-3-carboxylic acid 在 N,N-二甲基甲酰胺 草酰氯 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 4-((1H-1,2,4-triazol-1-yl)methyl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-1H-pyrazole-3-carbonyl chloride
  参考文献：
  名称：

  Heteroaryl-Pyrazole Derivatives as Cannabinoid CB1 Receptor Antagonists

  摘要：

  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。

  公开号：

  US20080081812A1

文献信息

• 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.