N-[4-[[C-[5-(4-chlorophenyl)-4-phenyl-3,4-dihydropyrazol-2-yl]-N-methylcarbonimidoyl]sulfamoyl]phenyl]acetamide | 1404117-40-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: N-[4-[[C-[5-(4-chlorophenyl)-4-phenyl-3,4-dihydropyrazol-2-yl]-N-methylcarbonimidoyl]sulfamoyl]phenyl]acetamide
• CAS: 1404117-40-3
• 化学式: C₂₅H₂₄ClN₅O₃S
• 分子量: 510.016
• InChiKey: LDBYYAUYORVLLI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-(4-硝基苯基)磺酰基氨基甲酸甲酯 在 吡啶 、 盐酸 、 五氯化磷 、 铁粉 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 水 、 氯苯 、 甲苯 为溶剂， 反应 8.0h， 生成 N-[4-[[C-[5-(4-chlorophenyl)-4-phenyl-3,4-dihydropyrazol-2-yl]-N-methylcarbonimidoyl]sulfamoyl]phenyl]acetamide
  参考文献：
  名称：

  JD-5006 and JD-5037: Peripherally restricted (PR) cannabinoid-1 receptor blockers related to SLV-319 (Ibipinabant) as metabolic disorder therapeutics devoid of CNS liabilities

  摘要：

  Analogs of SLV-319 (Ibipinibant), a CB1 receptor inverse agonist, were synthesized with functionality intended to limit brain exposure while maintaining the receptor affinity and selectivity of the parent compound. Structure activity relationships of this series, and pharmacology of two lead compounds, 16 (JD-5006) and 23 (JD-5037) showing little brain presence as indicated by tissue distribution and receptor occupancy studies, are described. Effects with one of these compounds on plasma triglyceride levels, liver weight and enzymes, glucose tolerance and insulin sensitivity support the approach that blockade of peripheral CB1 receptors is sufficient to produce many of the beneficial metabolic effects of globally active CB1 blockers. Thus, PR CB1 inverse agonists may indeed represent a safer alternative to highly brain-penetrant agents for the treatment of metabolic disorders, including diabetes, liver diseases, dyslipidemias, and obesity. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.004

文献信息

• JD-5006 and JD-5037: Peripherally restricted (PR) cannabinoid-1 receptor blockers related to SLV-319 (Ibipinabant) as metabolic disorder therapeutics devoid of CNS liabilities
  作者：Robert J. Chorvat、Jennifer Berbaum、Kristine Seriacki、John F. McElroy

  DOI：10.1016/j.bmcl.2012.08.004

  日期：2012.10

  Analogs of SLV-319 (Ibipinibant), a CB1 receptor inverse agonist, were synthesized with functionality intended to limit brain exposure while maintaining the receptor affinity and selectivity of the parent compound. Structure activity relationships of this series, and pharmacology of two lead compounds, 16 (JD-5006) and 23 (JD-5037) showing little brain presence as indicated by tissue distribution and receptor occupancy studies, are described. Effects with one of these compounds on plasma triglyceride levels, liver weight and enzymes, glucose tolerance and insulin sensitivity support the approach that blockade of peripheral CB1 receptors is sufficient to produce many of the beneficial metabolic effects of globally active CB1 blockers. Thus, PR CB1 inverse agonists may indeed represent a safer alternative to highly brain-penetrant agents for the treatment of metabolic disorders, including diabetes, liver diseases, dyslipidemias, and obesity. (C) 2012 Elsevier Ltd. All rights reserved.