N-(1-amino-2-methyl-1-oxopropan-2-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-N,4-dimethyl-1H-pyrazole-3-carboxamide | 1224836-52-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-(1-amino-2-methyl-1-oxopropan-2-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-N,4-dimethyl-1H-pyrazole-3-carboxamide
• CAS: 1224836-52-5
• 化学式: C₂₂H₂₁Cl₃N₄O₂
• 分子量: 479.793
• InChiKey: GCQSQPMFMVUECC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.14
• 重原子数：
  31.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  81.22
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  N-(1-amino-2-methyl-1-oxopropan-2-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-N,4-dimethyl-1H-pyrazole-3-carboxamide 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以0.67 g的产率得到2-[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]-1,5,5-trimethyl-1,5-dihydroimidazol-4-one
  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：

  2-甲基-2-(甲氨基)丙酰胺 、 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carbonyl chloride 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 15.0h， 生成 N-(1-amino-2-methyl-1-oxopropan-2-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-N,4-dimethyl-1H-pyrazole-3-carboxamide
  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