5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-ethylpyrazole-3-carboxylic acid chloride | 168273-07-2

• 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)-4-ethylpyrazole-3-carboxylic acid chloride
• 英文别名: 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-ethylpyrazole-3-carbonyl chloride
• CAS: 168273-07-2
• 化学式: C₁₈H₁₂Cl₄N₂O
• 分子量: 414.118
• InChiKey: HAJJECJNBBUQRC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  34.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-ethylpyrazole-3-carboxylic acid chloride 、 2-甲基-2-(甲氨基)丙酰胺 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 15.0h， 生成
  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
• 作为产物：
  描述：

  5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazole-3-carboxylic acid 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 甲苯 为溶剂， 生成 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-ethylpyrazole-3-carboxylic acid chloride
  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

• US5462960A
  申请人：——

  公开号：US5462960A

  公开（公告）日：1995-10-31
• 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.