5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-N'-hexanoyl-4-methylpyrazole-3-carbohydrazide | 1020796-92-2

• 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-chlorophenyl)-1-(2,4-dichlorophenyl)-N'-hexanoyl-4-methylpyrazole-3-carbohydrazide
• CAS: 1020796-92-2
• 化学式: C₂₃H₂₃Cl₃N₄O₂
• 分子量: 493.82
• InChiKey: IEBZNCRMVXAJQB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  76
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-N'-hexanoyl-4-methylpyrazole-3-carbohydrazide 在 伯吉斯试剂 作用下， 生成 2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)-5-pentyl-1,3,4-oxadiazole
  参考文献：
  名称：

  Biarylpyrazolyl Oxadiazole as Potent, Selective, Orally Bioavailable Cannabinoid-1 Receptor Antagonists for the Treatment of Obesity

  摘要：

  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.

  DOI：

  10.1021/jm800843r
• 作为产物：
  描述：

  己酰肼 、 1-(2,4-二氯苯基)-5-对氯苯基-4-甲基-吡唑-3-甲酸 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 生成 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-N'-hexanoyl-4-methylpyrazole-3-carbohydrazide
  参考文献：
  名称：

  Biarylpyrazolyl Oxadiazole as Potent, Selective, Orally Bioavailable Cannabinoid-1 Receptor Antagonists for the Treatment of Obesity

  摘要：

  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.

  DOI：

  10.1021/jm800843r

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.