N-((S)-1-oxo-1-(((S)-1-oxo-3-((S)-2-oxopyrrolidin-3-yl)propan-2-yl)amino)-3-phenyl-propan-2-yl)cinnamamide | 1065478-47-8

• 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-((S)-1-oxo-1-(((S)-1-oxo-3-((S)-2-oxopyrrolidin-3-yl)propan-2-yl)amino)-3-phenyl-propan-2-yl)cinnamamide
• 英文别名: cinnamoyl(E)-Phe-Ala((S)-2-oxopyrrolidin-3-yl)-al；(2S)-N-[(2S)-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl]-3-phenyl-2-[[(E)-3-phenylprop-2-enoyl]amino]propanamide
• CAS: 1065478-47-8
• 化学式: C₂₅H₂₇N₃O₄
• 分子量: 433.507
• InChiKey: GLPMVVAUDLVTNQ-QENTWVPSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-((S)-1-oxo-1-(((S)-1-oxo-3-((S)-2-oxopyrrolidin-3-yl)propan-2-yl)amino)-3-phenyl-propan-2-yl)cinnamamide 、 (苄氧羰基亚甲基)三苯基膦 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 生成 benzyl (S,E)-4-((S)-2-cinnamamido-3-phenylpropanamido)-5-((S)-2-oxopyrrolidin-3-yl)pent-2-enoate
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Peptidomimetic Aldehydes as Broad-Spectrum Inhibitors against Enterovirus and SARS-CoV-2

  摘要：

  DOI：

  10.1021/acs.jmedchem.0c02258
• 作为产物：
  描述：

  (alphaS,3S)-alpha-[(叔-丁基氧羰基)氨基]-2-氧代-3-吡咯烷丙酸甲酯 在 盐酸 、 sodium tetrahydroborate 、 碳酸氢钠 、 戴斯-马丁氧化剂 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 57.0h， 生成 N-((S)-1-oxo-1-(((S)-1-oxo-3-((S)-2-oxopyrrolidin-3-yl)propan-2-yl)amino)-3-phenyl-propan-2-yl)cinnamamide
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Peptidomimetic Aldehydes as Broad-Spectrum Inhibitors against Enterovirus and SARS-CoV-2

  摘要：

  DOI：

  10.1021/acs.jmedchem.0c02258

文献信息

• Design, synthesis, and evaluation of 3C protease inhibitors as anti-enterovirus 71 agents
  作者：Chih-Jung Kuo、Jiun-Jie Shie、Jim-Min Fang、Guei-Rung Yen、John T.-A. Hsu、Hun-Ge Liu、Sung-Nain Tseng、Shih-Cheng Chang、Ching-Yin Lee、Shin-Ru Shih、Po-Huang Liang

  DOI：10.1016/j.bmc.2008.06.015

  日期：2008.8

  Human enterovirus (EV) belongs to the picornavirus family, which consists of over 200 medically relevant viruses. A peptidomimetic inhibitor AG7088 was developed to inhibit the 3C protease of rhinovirus (a member of the family), a chymotrypsin-like protease required for viral replication, by forming a covalent bond with the active site Cys residue. In this study, we have prepared the recombinant 3C protease from EV71 (TW/2231/98), a particular strain which causes severe outbreaks in Asia, and developed inhibitors against the protease and the viral replication. For inhibitor design, the P3 group of AG7088, which is not interacting with the rhinovirus protease, was replaced with a series of cinnamoyl derivatives directly linked to P2 group through an amide bond to simplify the synthesis. While the replacement caused decreased potency, the activity can be largely improved by substituting the alpha,beta-unsaturated ester with an aldehyde at the P1' position. The best inhibitor 10b showed EC(50) of 18 nM without apparent toxicity (CC(50) > 25 mu M). Our study provides potent inhibitors of the EV71 3C protease as anti-EV71 agents and facilitates the combinatorial synthesis of derivatives for further improving the inhibitory activity. (C) 2008 Elsevier Ltd. All rights reserved.
• Design, Synthesis, and Biological Evaluation of Peptidomimetic Aldehydes as Broad-Spectrum Inhibitors against Enterovirus and SARS-CoV-2
  作者：Wenhao Dai、Dirk Jochmans、Hang Xie、Hang Yang、Jian Li、Haixia Su、Di Chang、Jiang Wang、Jingjing Peng、Lili Zhu、Yong Nian、Rolf Hilgenfeld、Hualiang Jiang、Kaixian Chen、Leike Zhang、Yechun Xu、Johan Neyts、Hong Liu

  DOI：10.1021/acs.jmedchem.0c02258

  日期：2022.2.24