N-acetonyl-3-fluoro-4-ethylbenzamide | 1016572-17-0

• 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-acetonyl-3-fluoro-4-ethylbenzamide
• 英文别名: 3-fluoro-4-methyl-N-(2-oxopropyl)benzamide
• CAS: 1016572-17-0
• 化学式: C₁₁H₁₂FNO₂
• 分子量: 209.22
• InChiKey: ZRYMGFMTYPDIIC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-acetonyl-3-fluoro-4-ethylbenzamide 、 methyl c-5-(4-iodobutyl)-2-methyl-1,3-dioxane-r-2-carboxylate 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以45%的产率得到methyl c-5-[5-(3-fluoro-4-methylbenzoylamino)-6-oxoheptyl]-2-methyl-1,3-dioxane-r-2-carboxylate
  参考文献：
  名称：

  Structure–activity studies on 1,3-dioxane-2-carboxylic acid derivatives, a novel class of subtype-selective peroxisome proliferator-activated receptor α (PPARα) agonists

  摘要：

  A series of 1,3-dioxane carboxylic acid derivatives was synthesized and evaluated for human PPAR transactivation activity. Structure-activity relationships on the phenyloxazole moiety of the lead compound 3 revealed that the introduction of small hydrophobic substituents at the 4-position of the terminal phenyl ring increased the PPAR alpha agonist activity, and that the oxazole heterocycle was essential to the maintenance of both potency and PPAR alpha subtype-selectivity. This investigation led to the identification of 14d (NS-220) and 14i as highly potent and selective human PPAR alpha agonists. In KK-A(y) type 2 diabetic mice, these compounds significantly lowered plasma triglyceride and very-low-density plus low-density lipoprotein cholesterol levels while simultaneously raising HDL cholesterol levels. Our results suggest that highly potent and subtype-selective PPAR alpha agonists will be promising drugs for the treatment of metabolic disorders in type 2 diabetes. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.10.007
• 作为产物：
  描述：

  3-fluoro-N-(2-hydroxypropyl)-4-methylbenzamide 在 pyridinium chlorochromate 作用下， 以 二氯甲烷 为溶剂， 以63%的产率得到N-acetonyl-3-fluoro-4-ethylbenzamide
  参考文献：
  名称：

  Structure–activity studies on 1,3-dioxane-2-carboxylic acid derivatives, a novel class of subtype-selective peroxisome proliferator-activated receptor α (PPARα) agonists

  摘要：

  A series of 1,3-dioxane carboxylic acid derivatives was synthesized and evaluated for human PPAR transactivation activity. Structure-activity relationships on the phenyloxazole moiety of the lead compound 3 revealed that the introduction of small hydrophobic substituents at the 4-position of the terminal phenyl ring increased the PPAR alpha agonist activity, and that the oxazole heterocycle was essential to the maintenance of both potency and PPAR alpha subtype-selectivity. This investigation led to the identification of 14d (NS-220) and 14i as highly potent and selective human PPAR alpha agonists. In KK-A(y) type 2 diabetic mice, these compounds significantly lowered plasma triglyceride and very-low-density plus low-density lipoprotein cholesterol levels while simultaneously raising HDL cholesterol levels. Our results suggest that highly potent and subtype-selective PPAR alpha agonists will be promising drugs for the treatment of metabolic disorders in type 2 diabetes. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.10.007

文献信息

• Structure–activity studies on 1,3-dioxane-2-carboxylic acid derivatives, a novel class of subtype-selective peroxisome proliferator-activated receptor α (PPARα) agonists
  作者：Tetsuo Asaki、Tomiyoshi Aoki、Taisuke Hamamoto、Yukiteru Sugiyama、Shinji Ohmachi、Kenji Kuwabara、Kohji Murakami、Makoto Todo

  DOI：10.1016/j.bmc.2007.10.007

  日期：2008.1

  A series of 1,3-dioxane carboxylic acid derivatives was synthesized and evaluated for human PPAR transactivation activity. Structure-activity relationships on the phenyloxazole moiety of the lead compound 3 revealed that the introduction of small hydrophobic substituents at the 4-position of the terminal phenyl ring increased the PPAR alpha agonist activity, and that the oxazole heterocycle was essential to the maintenance of both potency and PPAR alpha subtype-selectivity. This investigation led to the identification of 14d (NS-220) and 14i as highly potent and selective human PPAR alpha agonists. In KK-A(y) type 2 diabetic mice, these compounds significantly lowered plasma triglyceride and very-low-density plus low-density lipoprotein cholesterol levels while simultaneously raising HDL cholesterol levels. Our results suggest that highly potent and subtype-selective PPAR alpha agonists will be promising drugs for the treatment of metabolic disorders in type 2 diabetes. (C) 2007 Elsevier Ltd. All rights reserved.