ethyl 3-(4-((2-amino-6-(4-benzoylpiperazin-1-yl)pyrimidin-4-yl)oxy)phenyl)-2-methyl-2-phenoxypropanoate | 1186373-01-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: ethyl 3-(4-((2-amino-6-(4-benzoylpiperazin-1-yl)pyrimidin-4-yl)oxy)phenyl)-2-methyl-2-phenoxypropanoate
• CAS: 1186373-01-2
• 化学式: C₃₃H₃₅N₅O₅
• 分子量: 581.671
• InChiKey: UDHCQFVHJKNWRO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.76
• 重原子数：
  43.0
• 可旋转键数：
  10.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  120.11
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  ethyl 3-(4-((2-amino-6-(4-benzoylpiperazin-1-yl)pyrimidin-4-yl)oxy)phenyl)-2-methyl-2-phenoxypropanoate 在 水 、 potassium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 12.0h， 以95.5%的产率得到3-{4-[2-amino-6-(4-benzoylpiperazin-1-yl)pyrimidin-4-yloxy]phenyl}-2-methyl-2-phenoxypropionic acid
  参考文献：
  名称：

  Discovery of novel dual functional agent as PPARγ agonist and 11β-HSD1 inhibitor for the treatment of diabetes

  摘要：

  PPAR gamma and 11 beta-HSD1 are attractive therapeutic targets for type 2 diabetes. However, PPAR gamma agonists induce adipogenesis, which causes the side effect of weight gain, whereas 11 beta-HSD1 inhibitors prevent adipogenesis and may be beneficial for the treatment of obesity in diabetic patients. For the first time, we designed, synthesized a series of alpha-aryloxy-alpha-methylhydrocinnamic acids as dual functional agents which activate PPAR gamma and inhibit 11 beta-HSD1 simultaneously. The compound 11e exhibited the most potent inhibitory activity compared to that of the lead compound 2, with PPAR gamma (EC50 = 6.76 mu M) and 11 beta-HSD1 (IC50 = 0.76 mu M) in vitro. Molecular modeling study for compound 11e was also presented. Compound 11e showed excellent efficacy for lowering glucose, triglycerides, body fat, in well established mice and rats models of diabetes and obesity and had a favorable ADME profile. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.05.082
• 作为产物：
  描述：

  3-[4-(2-Amino-6-chloro-pyrimidin-4-yloxy)-phenyl]-2-methyl-2-phenoxy-propionic acid ethyl ester 、 1-苯甲酰哌嗪 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以74.6%的产率得到ethyl 3-(4-((2-amino-6-(4-benzoylpiperazin-1-yl)pyrimidin-4-yl)oxy)phenyl)-2-methyl-2-phenoxypropanoate
  参考文献：
  名称：

  Discovery of novel dual functional agent as PPARγ agonist and 11β-HSD1 inhibitor for the treatment of diabetes

  摘要：

  PPAR gamma and 11 beta-HSD1 are attractive therapeutic targets for type 2 diabetes. However, PPAR gamma agonists induce adipogenesis, which causes the side effect of weight gain, whereas 11 beta-HSD1 inhibitors prevent adipogenesis and may be beneficial for the treatment of obesity in diabetic patients. For the first time, we designed, synthesized a series of alpha-aryloxy-alpha-methylhydrocinnamic acids as dual functional agents which activate PPAR gamma and inhibit 11 beta-HSD1 simultaneously. The compound 11e exhibited the most potent inhibitory activity compared to that of the lead compound 2, with PPAR gamma (EC50 = 6.76 mu M) and 11 beta-HSD1 (IC50 = 0.76 mu M) in vitro. Molecular modeling study for compound 11e was also presented. Compound 11e showed excellent efficacy for lowering glucose, triglycerides, body fat, in well established mice and rats models of diabetes and obesity and had a favorable ADME profile. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.05.082