dibenzyl 2,4,6-trimethyl-1,4-dihydropyridine-3,5-dicarboxylate | 55536-70-4

• 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: dibenzyl 2,4,6-trimethyl-1,4-dihydropyridine-3,5-dicarboxylate
• 英文别名: 3,5-Dibenzyloxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridin；2,4,6-trimethyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid dibenzyl ester；2,4,6-Trimethyl-3,5-dicarbobenzyloxy-1,4-dihydropyridine
• CAS: 55536-70-4
• 化学式: C₂₄H₂₅NO₄
• 分子量: 391.467
• InChiKey: VGFHQHLORRXSTD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  溴乙酸异丙酯 、 dibenzyl 2,4,6-trimethyl-1,4-dihydropyridine-3,5-dicarboxylate 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 dibenzyl 1-(2-isopropoxy-2-oxoethyl)-2,4,6-trimethyl-1,4-dihydropyridine-3,5-dicarboxylate
  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：

  乙酸乙烯酯 、 乙酰丙酮苄酯 在 bovine porcine pancrease 、 formamide 作用下， 以 甲醇 为溶剂， 反应 48.0h， 以73%的产率得到dibenzyl 2,4,6-trimethyl-1,4-dihydropyridine-3,5-dicarboxylate
  参考文献：
  名称：

  1,4-Dihydropyridines: discovery of minimal AIEEgens and their mitochondrial imaging applications

  摘要：

  通过简单的生物催化过程合成了只含有单环的最小AIEEgens，成功地用于成像线粒体。

  DOI：

  10.1039/c6tb02135b

文献信息

• US4239893A
  申请人：——

  公开号：US4239893A

  公开（公告）日：1980-12-16
• US4317768A
  申请人：——

  公开号：US4317768A

  公开（公告）日：1982-03-02
• 1,4-Dihydropyridines: discovery of minimal AIEEgens and their mitochondrial imaging applications
  作者：Wei Zhang、Na Wang、Yan-Hong Liu、Shu-Yan Jiao、Wei-Wei Zhang、Xue-Mei Pu、Xiao-Qi Yu

  DOI：10.1039/c6tb02135b

  日期：——

  Minimal AIEEgens containing only a single ring were synthesized through a facile biocatalysis procedure and were successfully utilized in the imaging of mitochondria.

  通过简单的生物催化过程合成了只含有单环的最小AIEEgens，成功地用于成像线粒体。
• Design and synthesis of 1,4-dihydropyridine derivatives as BACE-1 inhibitors
  作者：Soo-Jeong Choi、Joong-Heui Cho、Isak Im、So-Deok Lee、Ji-Yeon Jang、Yu-Min Oh、Yong-Keun Jung、Eun-Seok Jeon、Yong-Chul Kim

  DOI：10.1016/j.ejmech.2010.02.046

  日期：2010.6

  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.