1-((4-chlorophenyl)(2,4-dichlorophenyl)methyl)piperazine | 512775-94-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-((4-chlorophenyl)(2,4-dichlorophenyl)methyl)piperazine
• 英文别名: 1-[(4-Chlorophenyl)-(2,4-dichlorophenyl)methyl]piperazine
• CAS: 512775-94-9
• 化学式: C₁₇H₁₇Cl₃N₂
• 分子量: 355.694
• InChiKey: YNAMEQMEKSNPLH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-((4-chlorophenyl)(2,4-dichlorophenyl)methyl)piperazine 、 环丙乙酸 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 1-(4-((4-氯苯基)(2,4-二氯苯基)甲基)哌嗪-1-基)-2-环丙基乙酮
  参考文献：
  名称：

  Design, synthesis and biological evaluation of piperazine analogues as CB1 cannabinoid receptor ligands

  摘要：

  After the CB1 receptor antagonist SR141716 (rimonabant) was previously reported to modulate food intake, CB1 antagonism has been considered as a new therapeutic target for the treatment of obesity. Several series of urea, carbamate, amide, sulfonamide and oxalamide derivatives based on 1-benzhydrylpiperazine scaffold were synthesized and tested for CB1 receptor binding affinity. The SAR studies to optimize the CB1 binding affinity led to the potent urea derivatives. After the additional SAR studies to optimize the substituents of diphenyl rings, the combination of 2-chlorophenyl and 4-chlorophenyl turned out to be the most potent scaffold. The CB2 binding affinity assay as well as functional assay was also conducted on these compounds. Herein we wish to introduce several novel CB1 antagonists with IC50 values less than 100 nM for the CB1 receptor binding. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.01.023
• 作为产物：
  描述：

  哌嗪 、 2,4,4'-trichloro-benzhydryl chloride 以 乙腈 为溶剂， 生成 1-((4-chlorophenyl)(2,4-dichlorophenyl)methyl)piperazine
  参考文献：
  名称：

  Design, synthesis and biological evaluation of piperazine analogues as CB1 cannabinoid receptor ligands

  摘要：

  After the CB1 receptor antagonist SR141716 (rimonabant) was previously reported to modulate food intake, CB1 antagonism has been considered as a new therapeutic target for the treatment of obesity. Several series of urea, carbamate, amide, sulfonamide and oxalamide derivatives based on 1-benzhydrylpiperazine scaffold were synthesized and tested for CB1 receptor binding affinity. The SAR studies to optimize the CB1 binding affinity led to the potent urea derivatives. After the additional SAR studies to optimize the substituents of diphenyl rings, the combination of 2-chlorophenyl and 4-chlorophenyl turned out to be the most potent scaffold. The CB2 binding affinity assay as well as functional assay was also conducted on these compounds. Herein we wish to introduce several novel CB1 antagonists with IC50 values less than 100 nM for the CB1 receptor binding. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.01.023

文献信息

• Discovery of benzhydrylpiperazine derivatives as CB1 receptor inverse agonists via privileged structure-based approach
  作者：Tao Meng、Jue Wang、Hongli Peng、Guanghua Fang、Min Li、Bing Xiong、Xin Xie、Yongliang Zhang、Xin Wang、Jingkang Shen

  DOI：10.1016/j.ejmech.2009.12.018

  日期：2010.3

  The present study describes the identification via privileged structure-based approach of the benzhydrylpiperazine moiety as a potential scaffold to develop novel CB1 receptor modulators. Efficient structural optimization of the initial four hit compounds led to a high quality lead series, represented by compound 6c. Compound 6c is a highly potent and selective CB1 receptor inverse agonist that is able to reduce body weight in diet-induced obese Sprague-Dawley rats. The preparation of privileged structure-based library, the progression from hit to lead, the structure-activity relationships in the lead series and in vitro and in vivo activity of compound 6c are discussed. (C) 2009 Elsevier Masson SAS. All rights reserved.