N-[(2S)-1-[[(4S,5S,7R)-5-hydroxy-2,7-dimethyl-8-(2-methylpropylamino)-8-oxooctan-4-yl]amino]-1-oxo-3-phenylpropan-2-yl]-3,5-dinitrobenzamide | 1173887-63-2

• 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: N-[(2S)-1-[[(4S,5S,7R)-5-hydroxy-2,7-dimethyl-8-(2-methylpropylamino)-8-oxooctan-4-yl]amino]-1-oxo-3-phenylpropan-2-yl]-3,5-dinitrobenzamide
• CAS: 1173887-63-2
• 化学式: C₃₀H₄₁N₅O₈
• 分子量: 599.684
• InChiKey: RPQSAFZRBJAIIJ-FLXBVFITSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  43
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  199
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  [(2R,4S,5S)-5-(N-Boc-L-phenylalanylamido)-4-hydroxy-2,7-dimethyloctanoyl] N'-isobutyl amide 、 3,5-二硝基苯甲酸 在 三氟乙酸 、 N-甲基吗啉 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.5h， 以19%的产率得到N-[(2S)-1-[[(4S,5S,7R)-5-hydroxy-2,7-dimethyl-8-(2-methylpropylamino)-8-oxooctan-4-yl]amino]-1-oxo-3-phenylpropan-2-yl]-3,5-dinitrobenzamide
  参考文献：
  名称：

  Synthesis and preliminary evaluation of peptidomimetic inhibitors of human β-secretase

  摘要：

  Based on the structure of OM99-2 and the X-ray crystal structure of its complex with beta-secretase, a series of compounds containing the Leu*Ala hydroxyethylene isostere as a scissile bond substitution were designed. 31 compounds were synthesized and their beta-secretase inhibition activities were measured. It was found that isobutyl group was a better R(3) substitution as C-terminus in our target compounds, and 4-nitrobenzyl group was the best R(2) side chain. With the aid of molecular modeling, the binding modes of compounds 9 and 22 with beta-secretase were compared. The result revealed a stronger bonding mode of 22 than 9. This explored that the optimal length of this series of peptidomimetic inhibitors was P3-P2'. The molecular weights of compounds with this length are around 600. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.01.044