2-chloro-N-(3-chloro-4-methylphenyl)-5-nitrobenzamide

• 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: 2-chloro-N-(3-chloro-4-methylphenyl)-5-nitrobenzamide
• 化学式: C₁₄H₁₀Cl₂N₂O₃
• mdl: MFCD01215210
• 分子量: 325.151
• InChiKey: XBJYRCAFIALUHQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  74.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-chloro-N-(3-chloro-4-methylphenyl)-5-nitrobenzamide 在 sodium tetrahydroborate 、 palladium on activated charcoal 、 溶剂黄146 、 三乙胺 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 5.0h， 生成 2-(3-(3-chloro-4-methylphenylcarbamoyl)-4-(piperidin-1-yl)phenyl)-1,3-dioxoisoindoline-5-carboxylic acid
  参考文献：
  名称：

  Structure–activity relationships for lipoprotein lipase agonists that lower plasma triglycerides in vivo

  摘要：

  The risk of cardiovascular events increases in individuals with elevated plasma triglyceride (TG) levels, therefore advocating the need for efficient TG-lowering drugs. In the blood circulation, TG levels are regulated by lipoprotein lipase (LPL), an unstable enzyme that is only active as a non-covalently associated homodimer. We recently reported on a N-phenylphthalimide derivative (1) that stabilizes LPL in vitro, and moderately lowers triglycerides in vivo (Biochem. Biophys. Res. Common. 2014, 450, 1063). Herein, we establish structure activity relationships of 51 N-phenylphthalimide analogs of the screening hit 1. In vitro evaluation highlighted that modifications on the phthalimide moiety were not tolerated and that lipophilic substituents on the central phenyl ring were functionally essential. The substitution pattern on the central phenyl ring also proved important to stabilize LPL However, in vitro testing demonstrated rapid degradation of the phthalimide fragment in plasma which was addressed by replacing the phthalimide scaffold with other heterocyclic fragments. The in vitro potency was retained or improved and substance 80 proved stable in plasma and efficiently lowered plasma TGs in vivo. 2015 The Authors. Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2015.08.058
• 作为产物：
  描述：

  2-氯-5-硝基苯甲酸 在 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 7.33h， 生成 2-chloro-N-(3-chloro-4-methylphenyl)-5-nitrobenzamide
  参考文献：
  名称：

  Structure–activity relationships for lipoprotein lipase agonists that lower plasma triglycerides in vivo

  摘要：

  The risk of cardiovascular events increases in individuals with elevated plasma triglyceride (TG) levels, therefore advocating the need for efficient TG-lowering drugs. In the blood circulation, TG levels are regulated by lipoprotein lipase (LPL), an unstable enzyme that is only active as a non-covalently associated homodimer. We recently reported on a N-phenylphthalimide derivative (1) that stabilizes LPL in vitro, and moderately lowers triglycerides in vivo (Biochem. Biophys. Res. Common. 2014, 450, 1063). Herein, we establish structure activity relationships of 51 N-phenylphthalimide analogs of the screening hit 1. In vitro evaluation highlighted that modifications on the phthalimide moiety were not tolerated and that lipophilic substituents on the central phenyl ring were functionally essential. The substitution pattern on the central phenyl ring also proved important to stabilize LPL However, in vitro testing demonstrated rapid degradation of the phthalimide fragment in plasma which was addressed by replacing the phthalimide scaffold with other heterocyclic fragments. The in vitro potency was retained or improved and substance 80 proved stable in plasma and efficiently lowered plasma TGs in vivo. 2015 The Authors. Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2015.08.058