4-methoxybenzyl 2-((6-amino-5-(((4-((1r,4r)-4-(2-methoxy-2-oxoethyl)cyclohexyl)phenyl)amino)methyl)pyrimidin-4-yl)oxy)acetate | 1450727-79-3

• 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: 4-methoxybenzyl 2-((6-amino-5-(((4-((1r,4r)-4-(2-methoxy-2-oxoethyl)cyclohexyl)phenyl)amino)methyl)pyrimidin-4-yl)oxy)acetate
• CAS: 1450727-79-3
• 化学式: C₃₀H₃₆N₄O₆
• 分子量: 548.639
• InChiKey: ZVVVEJCXYAECTL-AQYVVDRMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.64
• 重原子数：
  40.0
• 可旋转键数：
  12.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  134.89
• 氢给体数：
  2.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  4-methoxybenzyl 2-((6-amino-5-(((4-((1r,4r)-4-(2-methoxy-2-oxoethyl)cyclohexyl)phenyl)amino)methyl)pyrimidin-4-yl)oxy)acetate 在 三氟乙酸 、 4-二甲氨基吡啶 、 N,N'-羰基二咪唑 、 lithium hydroxide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 1,4-二氧六环 、 水 为溶剂， 反应 26.0h， 以3.3 mg的产率得到{trans-4-[4-(4-amino-7-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl]cyclohexyl}acetic acid
  参考文献：
  名称：

  Defining the key pharmacophore elements of PF-04620110: Discovery of a potent, orally-active, neutral DGAT-1 inhibitor

  摘要：

  DGAT-1 is an enzyme that catalyzes the final step in triglyceride synthesis. mRNA knockout experiments in rodent models suggest that inhibitors of this enzyme could be of value in the treatment of obesity and type II diabetes. The carboxylic acid-based DGAT-1 inhibitor 1 was advanced to clinical trials for the treatment of type 2 diabetes, despite of the low passive permeability of 1. Because of questions relating to the potential attenuation of distribution and efficacy of a poorly permeable agent, efforts were initiated to identify compounds with improved permeability. Replacement of the acid moiety in 1 with an oxadiazole led to the discovery of 52, which possesses substantially improved passive permeability. The resulting pharmacodynamic profile of this neutral DGAT-1 inhibitor was found to be similar to 1 at comparable plasma exposures. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.06.045
• 作为产物：
  描述：

  4-Methoxybenzyl 2-hydroxyacetate 在 sodium hydride 作用下， 以 四氢呋喃 、 1,2-二氯乙烷 、 mineral oil 为溶剂， 反应 62.25h， 生成 4-methoxybenzyl 2-((6-amino-5-(((4-((1r,4r)-4-(2-methoxy-2-oxoethyl)cyclohexyl)phenyl)amino)methyl)pyrimidin-4-yl)oxy)acetate
  参考文献：
  名称：

  Defining the key pharmacophore elements of PF-04620110: Discovery of a potent, orally-active, neutral DGAT-1 inhibitor

  摘要：

  DGAT-1 is an enzyme that catalyzes the final step in triglyceride synthesis. mRNA knockout experiments in rodent models suggest that inhibitors of this enzyme could be of value in the treatment of obesity and type II diabetes. The carboxylic acid-based DGAT-1 inhibitor 1 was advanced to clinical trials for the treatment of type 2 diabetes, despite of the low passive permeability of 1. Because of questions relating to the potential attenuation of distribution and efficacy of a poorly permeable agent, efforts were initiated to identify compounds with improved permeability. Replacement of the acid moiety in 1 with an oxadiazole led to the discovery of 52, which possesses substantially improved passive permeability. The resulting pharmacodynamic profile of this neutral DGAT-1 inhibitor was found to be similar to 1 at comparable plasma exposures. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.06.045