(1S,2R)-N-{1-benzyl-2-hydroxy-3-(S)-[2-(1-benzylpiperidin-4-yl)ethylamino]-propyl}-N',N'-dipropyl-5-[methyl(methylsulfonyl)amino]isophthalamide | 1116134-50-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (1S,2R)-N-{1-benzyl-2-hydroxy-3-(S)-[2-(1-benzylpiperidin-4-yl)ethylamino]-propyl}-N',N'-dipropyl-5-[methyl(methylsulfonyl)amino]isophthalamide
• 英文别名: 1-N-[(2S,3R)-4-[2-(1-benzylpiperidin-4-yl)ethylamino]-3-hydroxy-1-phenylbutan-2-yl]-5-[methyl(methylsulfonyl)amino]-3-N,3-N-dipropylbenzene-1,3-dicarboxamide
• CAS: 1116134-50-9
• 化学式: C₄₀H₅₇N₅O₅S
• 分子量: 719.989
• InChiKey: QQBIHVNKZCDPGZ-QPPIDDCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  51
• 可旋转键数：
  19
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  131
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-(dipropylcarbamoyl)-5-[methyl(methylsulfonyl)amino]benzoic acid 、 在 盐酸 、 水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 (1S,2R)-N-{1-benzyl-2-hydroxy-3-(S)-[2-(1-benzylpiperidin-4-yl)ethylamino]-propyl}-N',N'-dipropyl-5-[methyl(methylsulfonyl)amino]isophthalamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel dual inhibitors of acetylcholinesterase and β-secretase

  摘要：

  To explore novel effective drugs for the treatment of Alzheimer's disease (AD), a series of dual inhibitors of acetylcholineterase (AChE) and beta-secretase (BACE-1) were designed based on the multi-target-directed ligands strategy. Among them, inhibitor 28 exhibited good dual potency in enzyme inhibitory potency assay (BACE-1: IC50 = 0.567 mu M; AChE: IC50 = 1.83 mu M), and also showed excellent inhibitory effects on Ab production of APP transfected HEK293 cells (IC50 = 98.7 nM) and mild protective effect against hydrogen peroxide (H2O2)-induced PC12 cell injury. Encouragingly, intracerebroventricular injection of 28 into amyloid precursor protein (APP) transgenic mice caused a 29% reduction of A beta(1-40) production. Therefore, 28 was demonstrated as a good lead compound for the further study and more importantly, the strategy of AChE and BACE-1 dual inhibitors might be a promising direction for developing novel drugs for AD patients. (c) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.12.067

文献信息

• Design, synthesis and biological evaluation of novel dual inhibitors of acetylcholinesterase and β-secretase
  作者：Yiping Zhu、Kun Xiao、Lanping Ma、Bin Xiong、Yan Fu、Haiping Yu、Wei Wang、Xin Wang、Dingyu Hu、Hongli Peng、Jingya Li、Qi Gong、Qian Chai、Xican Tang、Haiyan Zhang、Jia Li、Jingkang Shen

  DOI：10.1016/j.bmc.2008.12.067

  日期：2009.2

  To explore novel effective drugs for the treatment of Alzheimer's disease (AD), a series of dual inhibitors of acetylcholineterase (AChE) and beta-secretase (BACE-1) were designed based on the multi-target-directed ligands strategy. Among them, inhibitor 28 exhibited good dual potency in enzyme inhibitory potency assay (BACE-1: IC50 = 0.567 mu M; AChE: IC50 = 1.83 mu M), and also showed excellent inhibitory effects on Ab production of APP transfected HEK293 cells (IC50 = 98.7 nM) and mild protective effect against hydrogen peroxide (H2O2)-induced PC12 cell injury. Encouragingly, intracerebroventricular injection of 28 into amyloid precursor protein (APP) transgenic mice caused a 29% reduction of A beta(1-40) production. Therefore, 28 was demonstrated as a good lead compound for the further study and more importantly, the strategy of AChE and BACE-1 dual inhibitors might be a promising direction for developing novel drugs for AD patients. (c) 2009 Elsevier Ltd. All rights reserved.