tert-butyl N-[(2S)-2-[[(2S)-2-[(3,5-dimethylpyrazol-1-yl)methyl]butanoyl]amino]-3-[[(4S,5S,7R)-5-hydroxy-2,7-dimethyl-8-[[(2S)-3-methyl-1-(2-methylpropylamino)-1-oxobutan-2-yl]amino]-8-oxooctan-4-yl]amino]-3-oxopropyl]carbamate | 881009-12-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: tert-butyl N-[(2S)-2-[[(2S)-2-[(3,5-dimethylpyrazol-1-yl)methyl]butanoyl]amino]-3-[[(4S,5S,7R)-5-hydroxy-2,7-dimethyl-8-[[(2S)-3-methyl-1-(2-methylpropylamino)-1-oxobutan-2-yl]amino]-8-oxooctan-4-yl]amino]-3-oxopropyl]carbamate
• CAS: 881009-12-7
• 化学式: C₃₇H₆₇N₇O₇
• 分子量: 721.982
• InChiKey: ZFEBFROZYQKAQP-LJXNYGQKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  51
• 可旋转键数：
  22
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  193
• 氢给体数：
  6
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-(N-Cbz)-3-(N-Boc)-2,3-二氨基丙酸 在 20% palladium hydroxide-activated charcoal 、 四丁基氟化铵 、 氢气 、 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 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 45.0h， 生成 tert-butyl N-[(2S)-2-[[(2S)-2-[(3,5-dimethylpyrazol-1-yl)methyl]butanoyl]amino]-3-[[(4S,5S,7R)-5-hydroxy-2,7-dimethyl-8-[[(2S)-3-methyl-1-(2-methylpropylamino)-1-oxobutan-2-yl]amino]-8-oxooctan-4-yl]amino]-3-oxopropyl]carbamate
  参考文献：
  名称：

  Structure-based design, synthesis and biological evaluation of novel β-secretase inhibitors containing a pyrazole or thiazole moiety as the P3 ligand

  摘要：

  We describe structure-based design, synthesis, and biological evaluation of a series of novel inhibitors bearing a pyrazole (compounds 3a-h) or a thiazole moiety (compounds 4a-e) as the P3 ligand. We have also explored Boc-beta-amino-L-alanine as a novel P2 ligand. A number of inhibitors have displayed b-secretase inhibitory potency. Inhibitor 4c has shown potent BACE1 inhibitory activity, K-i = 0.25 nM, cellular EC50 of 194 nM, and displayed good selectivity over BACE2. A model of 4c was created based upon the X-ray structure of 2-bound beta-secretase which revealed critical interactions in the active site. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.11.087

文献信息

• Amino-Containing Compounds Which Inhibit Memapsin 2 Beta-Secretase Activity and Methods of Use Thereof
  申请人：Ghosh Arun K.

  公开号：US20080125467A1

  公开（公告）日：2008-05-29

  The present invention provides novel beta-secretase inhibitors and methods for their use, including methods of treating of Alzheimer's disease.

  本发明提供了新型β-分泌酶抑制剂及其使用方法，包括治疗阿尔茨海默病的方法。
• US7659289B2
  申请人：——

  公开号：US7659289B2

  公开（公告）日：2010-02-09
• Structure-based design, synthesis and biological evaluation of novel β-secretase inhibitors containing a pyrazole or thiazole moiety as the P3 ligand
  作者：Arun K. Ghosh、Margherita Brindisi、Yu-Chen Yen、Xiaoming Xu、Xiangping Huang、Thippeswamy Devasamudram、Geoffrey Bilcer、Hui Lei、Gerald Koelsch、Andrew D. Mesecar、Jordan Tang

  DOI：10.1016/j.bmcl.2014.11.087

  日期：2015.2

  We describe structure-based design, synthesis, and biological evaluation of a series of novel inhibitors bearing a pyrazole (compounds 3a-h) or a thiazole moiety (compounds 4a-e) as the P3 ligand. We have also explored Boc-beta-amino-L-alanine as a novel P2 ligand. A number of inhibitors have displayed b-secretase inhibitory potency. Inhibitor 4c has shown potent BACE1 inhibitory activity, K-i = 0.25 nM, cellular EC50 of 194 nM, and displayed good selectivity over BACE2. A model of 4c was created based upon the X-ray structure of 2-bound beta-secretase which revealed critical interactions in the active site. (C) 2014 Elsevier Ltd. All rights reserved.