2-(4-(2-(2-methoxyethoxy)ethoxy)-3-(p-tolylcarbamoyl)phenyl)-1,3-dioxoisoindoline-5-carboxylic acid

• 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-(4-(2-(2-methoxyethoxy)ethoxy)-3-(p-tolylcarbamoyl)phenyl)-1,3-dioxoisoindoline-5-carboxylic acid
• 英文别名: 2-[4-[2-(2-Methoxyethoxy)ethoxy]-3-[(4-methylphenyl)carbamoyl]phenyl]-1,3-dioxoisoindole-5-carboxylic acid；2-[4-[2-(2-methoxyethoxy)ethoxy]-3-[(4-methylphenyl)carbamoyl]phenyl]-1,3-dioxoisoindole-5-carboxylic acid
• 化学式: C₂₈H₂₆N₂O₈
• 分子量: 518.523
• InChiKey: BPZBPKNPLURGHX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  38
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  132
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  二乙二醇单甲醚 在 sodium tetrahydroborate 、 palladium on activated charcoal 、 溶剂黄146 、 potassium hydroxide 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 反应 29.0h， 生成 2-(4-(2-(2-methoxyethoxy)ethoxy)-3-(p-tolylcarbamoyl)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

文献信息

• [EN] NEW PLASMA LIPID LOWERING AGENTS<br/>[FR] NOUVEAUX AGENTS ABAISSANT LES TAUX DES LIPIDES PLASMATIQUES
  申请人：LIPIGON PHARMACEUTICALS AB

  公开号：WO2015187082A1

  公开（公告）日：2015-12-10

  The present invention relates to new plasma lipid lowering compounds and pharmacological compositions,and their use in the prophylaxis, prevention and treatment of hyperlipidemia, including hypertriglyceridemia, hyperlipoproteinemia, and hypercholesterolemia, as well as hyperlipidemia-related diseases.

  本发明涉及新的降低血浆脂质的化合物和药物组合物，以及它们在预防、预防和治疗高脂血症，包括高三酸甘油酯血症、高脂蛋白血症和高胆固醇血症，以及与高脂血症相关的疾病中的应用。