5-(benzyloxycarbonyl)-1-(2-isopropoxy-2-oxoethyl)-2,4,6-trimethyl-1,4-dihydro pyridine-3-carboxylic acid | 1229575-53-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 5-(benzyloxycarbonyl)-1-(2-isopropoxy-2-oxoethyl)-2,4,6-trimethyl-1,4-dihydro pyridine-3-carboxylic acid
• 英文别名: 2,4,6-trimethyl-1-(2-oxo-2-propan-2-yloxyethyl)-5-phenylmethoxycarbonyl-4H-pyridine-3-carboxylic acid
• CAS: 1229575-53-4
• 化学式: C₂₂H₂₇NO₆
• 分子量: 401.459
• InChiKey: BJFUNVVQMGPBBS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  93.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-(benzyloxycarbonyl)-1-(2-isopropoxy-2-oxoethyl)-2,4,6-trimethyl-1,4-dihydro pyridine-3-carboxylic acid 、 (2R,3S)-3-amino-1-(cyclopropylamino)-4-phenylbutan-2-ol 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 以37%的产率得到benzyl 5-((2S,3R)-4-(cyclopropylamino)-3-hydroxy-1-phenylbutan-2-ylcarbamoyl)-1-(2-isopropoxy-2-oxoethyl)-2,4,6-trimethyl-1,4-dihydropyridine-3-carboxylate
  参考文献：
  名称：

  Design and synthesis of 1,4-dihydropyridine derivatives as BACE-1 inhibitors

  摘要：

  BACE-1 has been shown to be an attractive therapeutic target in Alzheimer's disease (AD). Using a 1,4-dihydropyridine (DHP) scaffold, we synthesized new inhibitors of BACE-1 by modifying the known BACE inhibitor 2 containing a hydroxyethylamine (HEA) motif. Using structure-based drug design based on computer-aided molecular docking, the isophthalamide ring of 2 was replaced with a 1,4-dihydropyridine ring as a brain-targeting strategy. Several of the new dihydropyridine derivatives were synthesized and their BACE-1-inhibitory activities were evaluated using a cell-based, reporter gene assay system that measures the cleavage of alkaline phosphatase (AP)-APP fusion protein by BACE-1. Most of the 1,4-DHP analogs showed BACE-1-inhibitory activities with IC50 values in the range 8-30 mu M, suggesting that the 1,4-DHP skeleton may be utilized to develop brain-targeting BACE-1 inhibitors.

  DOI：

  10.1016/j.ejmech.2010.02.046
• 作为产物：
  描述：

  dibenzyl 1-(2-isopropoxy-2-oxoethyl)-2,4,6-trimethyl-1,4-dihydropyridine-3,5-dicarboxylate 在 aluminum (III) chloride 、 苯甲醚 、 水 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 5-(benzyloxycarbonyl)-1-(2-isopropoxy-2-oxoethyl)-2,4,6-trimethyl-1,4-dihydro pyridine-3-carboxylic acid
  参考文献：
  名称：

  Design and synthesis of 1,4-dihydropyridine derivatives as BACE-1 inhibitors

  摘要：

  BACE-1 has been shown to be an attractive therapeutic target in Alzheimer's disease (AD). Using a 1,4-dihydropyridine (DHP) scaffold, we synthesized new inhibitors of BACE-1 by modifying the known BACE inhibitor 2 containing a hydroxyethylamine (HEA) motif. Using structure-based drug design based on computer-aided molecular docking, the isophthalamide ring of 2 was replaced with a 1,4-dihydropyridine ring as a brain-targeting strategy. Several of the new dihydropyridine derivatives were synthesized and their BACE-1-inhibitory activities were evaluated using a cell-based, reporter gene assay system that measures the cleavage of alkaline phosphatase (AP)-APP fusion protein by BACE-1. Most of the 1,4-DHP analogs showed BACE-1-inhibitory activities with IC50 values in the range 8-30 mu M, suggesting that the 1,4-DHP skeleton may be utilized to develop brain-targeting BACE-1 inhibitors.

  DOI：

  10.1016/j.ejmech.2010.02.046