(4S)-(N-((N-acetyl-L-isoleucyl)-L-threonyl-L-alanyl amino)-2,2-difluoro-3-oxo-4-aminopentanoyl)glycine

• 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: (4S)-(N-((N-acetyl-L-isoleucyl)-L-threonyl-L-alanyl amino)-2,2-difluoro-3-oxo-4-aminopentanoyl)glycine
• 英文别名: 2-[[(4S)-4-[[(2S)-2-[[(2S,3R)-2-[[(2S,3S)-2-acetamido-3-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]propanoyl]amino]-2,2-difluoro-3-oxopentanoyl]amino]acetic acid
• 化学式: C₂₂H₃₅F₂N₅O₉
• 分子量: 551.545
• InChiKey: AQGOQBYAZBTQQB-CVYVPXSGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  38
• 可旋转键数：
  15
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  220
• 氢给体数：
  7
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  芴甲氧羰基-O-苄基-L-苏氨酸 在 哌啶 、 palladium 10% on activated carbon 、 氢气 、 1-羟基苯并三唑 、 戴斯-马丁氧化剂 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N-甲基吡咯烷酮 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 53.3h， 生成 (4S)-(N-((N-acetyl-L-isoleucyl)-L-threonyl-L-alanyl amino)-2,2-difluoro-3-oxo-4-aminopentanoyl)glycine
  参考文献：
  名称：

  Rational design of the first difluorostatone-based PfSUB1 inhibitors

  摘要：

  The etiological agent of the most dangerous form of malaria, Plasmodium falciparum, has developed resistance or reduced sensitivity to the majority of the drugs available to treat this deadly disease. Innovative antimalarial therapies are therefore urgently required. P. falciparum serine protease subtilisin-like protease 1 (PfSUB1) has been identified as a key enzyme for merozoite egress from red blood cells and invasion. We present herein the rational design, synthesis, and biological evaluation of novel and potent difluorostatone-based inhibitors. Our bioinformatic-driven studies resulted in the identification of compounds 1a, b as potent and selective PfSUB1 inhibitors. The enzyme/inhibitor interaction pattern herein proposed will pave the way to the future optimization of this class of promising enzyme inhibitors. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.05.044

文献信息

• Rational design of the first difluorostatone-based PfSUB1 inhibitors
  作者：Simone Giovani、Maria Penzo、Simone Brogi、Margherita Brindisi、Sandra Gemma、Ettore Novellino、Luisa Savini、Michael J. Blackman、Giuseppe Campiani、Stefania Butini

  DOI：10.1016/j.bmcl.2014.05.044

  日期：2014.8

  The etiological agent of the most dangerous form of malaria, Plasmodium falciparum, has developed resistance or reduced sensitivity to the majority of the drugs available to treat this deadly disease. Innovative antimalarial therapies are therefore urgently required. P. falciparum serine protease subtilisin-like protease 1 (PfSUB1) has been identified as a key enzyme for merozoite egress from red blood cells and invasion. We present herein the rational design, synthesis, and biological evaluation of novel and potent difluorostatone-based inhibitors. Our bioinformatic-driven studies resulted in the identification of compounds 1a, b as potent and selective PfSUB1 inhibitors. The enzyme/inhibitor interaction pattern herein proposed will pave the way to the future optimization of this class of promising enzyme inhibitors. (C) 2014 Elsevier Ltd. All rights reserved.