isopropyl 2-(3-((2S,3R)-3-hydroxy-4-(3-methoxyphenylamino)-1-phenylbutan-2-ylcarbamoyl)-5-((R)-1-phenylethylcarbamoyl)-4-propylpyridin-1(4H)-yl)acetate | 1229576-10-6

• 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: isopropyl 2-(3-((2S,3R)-3-hydroxy-4-(3-methoxyphenylamino)-1-phenylbutan-2-ylcarbamoyl)-5-((R)-1-phenylethylcarbamoyl)-4-propylpyridin-1(4H)-yl)acetate
• 英文别名: propan-2-yl 2-[3-[[(2S,3R)-3-hydroxy-4-(3-methoxyanilino)-1-phenylbutan-2-yl]carbamoyl]-5-[[(1R)-1-phenylethyl]carbamoyl]-4-propyl-4H-pyridin-1-yl]acetate
• CAS: 1229576-10-6
• 化学式: C₄₀H₅₀N₄O₆
• 分子量: 682.86
• InChiKey: FGPAWXPJMYQIHY-WJIGXWHBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  50
• 可旋转键数：
  18
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  129
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (2R,3S)-3-amino-1-(3-methoxyanilino)-4-phenylbutan-2-ol 、 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 isopropyl 2-(3-((2S,3R)-3-hydroxy-4-(3-methoxyphenylamino)-1-phenylbutan-2-ylcarbamoyl)-5-((R)-1-phenylethylcarbamoyl)-4-propylpyridin-1(4H)-yl)acetate
  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

文献信息

• 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.