N-{4-(diethylamino)phenyl}-2-(2-{indolin-1-yl}-2-oxoethoxy)benzamide

• 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: N-{4-(diethylamino)phenyl}-2-(2-{indolin-1-yl}-2-oxoethoxy)benzamide
• 英文别名: N-[4-(diethylamino)phenyl]-2-[2-(2,3-dihydro-1H-indol-1-yl)-2-oxoethoxy]benzamide；N-[4-(diethylamino)phenyl]-2-[2-(2,3-dihydroindol-1-yl)-2-oxoethoxy]benzamide
• 化学式: C₂₇H₂₉N₃O₃
• 分子量: 443.546
• InChiKey: GSEHLZQOBINPDT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  61.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  水杨酸 在 氯化亚砜 、 potassium carbonate 、 potassium iodide 作用下， 以 氯化亚砜 、 二氯甲烷 、 丙酮 为溶剂， 反应 3.0h， 生成 N-{4-(diethylamino)phenyl}-2-(2-{indolin-1-yl}-2-oxoethoxy)benzamide
  参考文献：
  名称：

  Identification of dual PPARα/γ agonists and their effects on lipid metabolism

  摘要：

  The three peroxisome proliferator-activated receptor (PPAR) isoforms; PPAR alpha, PPAR gamma and PPAR delta, play central roles in lipid metabolism and glucose homeostasis. Dual PPAR alpha/gamma agonists, which stimulate both PPAR alpha and PPAR gamma isoforms to similar extents, are gaining popularity as it is believed that they are able to ameliorate the unwanted side effects of selective PPAR alpha and PPAR gamma agonists; and may also be used to treat dyslipidemia and type 2 diabetes mellitus simultaneously. In this study, virtual screening of natural product libraries, using both structure-based and ligand-based drug discovery approaches, identified ten potential dual PPAR alpha/gamma agonist lead compounds (9-13 and 16-20). In vitro assays confirmed these compounds to show no statistically significant toxicity to cells, with the exception of compound 12 which inhibited cell growth to 74.5% +/- 3.5 and 54.1% +/- 3.7 at 50 mu M and 100 mu M, respectively. In support of their potential as dual PPAR alpha/gamma agonists, all ten compounds upregulated the expression of cholesterol transporters ABCA1 and ABCG1 in THP-1 macrophages, with indoline derivative 16 producing the greatest elevation (2.3-fold; 3.3-fold, respectively). Furthermore, comparable to the activity of established PPAR alpha and PPAR gamma agonists, compound 16 stimulated triacylglycerol accumulation during 3T3-L1 adipocyte differentiation as well as fatty acid beta-oxidation in HuH7 hepatocytes. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.11.013

文献信息

• Identification of dual PPARα/γ agonists and their effects on lipid metabolism
  作者：Quanqing Gao、Jacky Hanh、Linda Váradi、Rose Cairns、Helena Sjöström、Vivian W.Y. Liao、Peta Wood、Seher Balaban、Jennifer Ai Ong、Hsuan-Yu Jennifer Lin、Felcia Lai、Andrew J. Hoy、Thomas Grewal、Paul W. Groundwater、David E. Hibbs

  DOI：10.1016/j.bmc.2015.11.013

  日期：2015.12

  The three peroxisome proliferator-activated receptor (PPAR) isoforms; PPAR alpha, PPAR gamma and PPAR delta, play central roles in lipid metabolism and glucose homeostasis. Dual PPAR alpha/gamma agonists, which stimulate both PPAR alpha and PPAR gamma isoforms to similar extents, are gaining popularity as it is believed that they are able to ameliorate the unwanted side effects of selective PPAR alpha and PPAR gamma agonists; and may also be used to treat dyslipidemia and type 2 diabetes mellitus simultaneously. In this study, virtual screening of natural product libraries, using both structure-based and ligand-based drug discovery approaches, identified ten potential dual PPAR alpha/gamma agonist lead compounds (9-13 and 16-20). In vitro assays confirmed these compounds to show no statistically significant toxicity to cells, with the exception of compound 12 which inhibited cell growth to 74.5% +/- 3.5 and 54.1% +/- 3.7 at 50 mu M and 100 mu M, respectively. In support of their potential as dual PPAR alpha/gamma agonists, all ten compounds upregulated the expression of cholesterol transporters ABCA1 and ABCG1 in THP-1 macrophages, with indoline derivative 16 producing the greatest elevation (2.3-fold; 3.3-fold, respectively). Furthermore, comparable to the activity of established PPAR alpha and PPAR gamma agonists, compound 16 stimulated triacylglycerol accumulation during 3T3-L1 adipocyte differentiation as well as fatty acid beta-oxidation in HuH7 hepatocytes. (c) 2015 Elsevier Ltd. All rights reserved.