ethyl (E,4S)-4-(naphthalene-2-carbonylamino)-5-[(3S)-2-oxopyrrolidin-3-yl]pent-2-enoate

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: ethyl (E,4S)-4-(naphthalene-2-carbonylamino)-5-[(3S)-2-oxopyrrolidin-3-yl]pent-2-enoate
• 化学式: C₂₂H₂₄N₂O₄
• 分子量: 380.444
• InChiKey: BWGUINYTRHIFSE-NDUHVBCRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  84.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-[(1S)-1-(羟基甲基)-2-[(3S)-2-氧代-3-吡咯烷基]乙基]-氨基甲酸叔-丁酯 在 盐酸 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 2-碘酰基苯甲酸 作用下， 以 乙醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 ethyl (E,4S)-4-(naphthalene-2-carbonylamino)-5-[(3S)-2-oxopyrrolidin-3-yl]pent-2-enoate
  参考文献：
  名称：

  Structure-Based Design of a Parallel Synthetic Array Directed Toward the Discovery of Irreversible Inhibitors of Human Rhinovirus 3C Protease

  摘要：

  Utilizing the tools of parallel synthesis and structure-based design, a new class of Michael acceptor-containing, irreversible inhibitors of human rhinovirus 3C protease (HRV 3CP) was discovered. These inhibitors are shown to inhibit HRV-14 3CP with rates of inactivation ranging from 886 to 31400 M-1 sec(-1). These inhibitors exhibit antiviral activity when tested against HRV-14 infected H1-HeLa cells, with EC50 values ranging from 1.94 to 0.15 muM. No cytotoxicity was observed at the limits of the assay concentration. A crystal structure of one of the more potent inhibitors covalently bound to HRV-2 3CP is detailed, These compounds were also tested against HRV serotypes other than type 14 and were found to have highly variable activities.

  DOI：

  10.1021/jm010435c

文献信息

• Structure-Based Design of a Parallel Synthetic Array Directed Toward the Discovery of Irreversible Inhibitors of Human Rhinovirus 3C Protease
  作者：Theodore O. Johnson、Ye Hua、Hiep T. Luu、Edward L. Brown、Fora Chan、Shao Song Chu、Peter S. Dragovich、Brian W. Eastman、Rose Ann Ferre、Shella A. Fuhrman、Thomas F. Hendrickson、Fausto C. Maldonado、David A. Matthews、James W. Meador、Amy K. Patick、Siegfried H. Reich、Donald J. Skalitzky、Stephen T. Worland、Michelle Yang、Leora S. Zalman

  DOI：10.1021/jm010435c

  日期：2002.5.1

  Utilizing the tools of parallel synthesis and structure-based design, a new class of Michael acceptor-containing, irreversible inhibitors of human rhinovirus 3C protease (HRV 3CP) was discovered. These inhibitors are shown to inhibit HRV-14 3CP with rates of inactivation ranging from 886 to 31400 M-1 sec(-1). These inhibitors exhibit antiviral activity when tested against HRV-14 infected H1-HeLa cells, with EC50 values ranging from 1.94 to 0.15 muM. No cytotoxicity was observed at the limits of the assay concentration. A crystal structure of one of the more potent inhibitors covalently bound to HRV-2 3CP is detailed, These compounds were also tested against HRV serotypes other than type 14 and were found to have highly variable activities.