2-[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]-1,3-diazaspiro[4.5]dec-1-en-4-one | 1170700-94-3

• 英文名称: 2-[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]-1,3-diazaspiro[4.5]dec-1-en-4-one
• 英文别名: 2-[5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4-ethyl-1H-pyrazol-3-yl]-1,3-diaza-spiro[4.5]dec-1-en-4-one；2-[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-ethylpyrazol-3-yl]-1,3-diazaspiro[4.5]dec-1-en-4-one
• CAS: 1170700-94-3
• 化学式: C₂₅H₂₃Cl₃N₄O
• 分子量: 501.843
• InChiKey: KFXQPGMMLBLGPQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  59.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  在 三氯氧磷 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 4.0h， 以47%的产率得到2-[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]-1,3-diazaspiro[4.5]dec-1-en-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