methyl 2-{2-[3,4-(methylenedioxy)cinnamoyl]amino-1-oxo-3-phenyl}propyl-amino-3-(2-oxo-3-pyrrolidinyl)-propionate | 1065478-31-0

• 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: methyl 2-{2-[3,4-(methylenedioxy)cinnamoyl]amino-1-oxo-3-phenyl}propyl-amino-3-(2-oxo-3-pyrrolidinyl)-propionate
• CAS: 1065478-31-0
• 化学式: C₂₇H₂₉N₃O₇
• 分子量: 507.543
• InChiKey: OOAGLAUKPSWHMB-DGVMCGEFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.34
• 重原子数：
  37.0
• 可旋转键数：
  10.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  132.06
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  methyl 2-{2-[3,4-(methylenedioxy)cinnamoyl]amino-1-oxo-3-phenyl}propyl-amino-3-(2-oxo-3-pyrrolidinyl)-propionate 在 锂硼氢 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  Design, synthesis, and evaluation of 3C protease inhibitors as anti-enterovirus 71 agents

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2008.06.015
• 作为产物：
  描述：

  (E)-3-(1,3-benzodioxol-5-yl)acryloyl chloride 、 (S)-methyl 2-((S)-2-amino-3-phen-ylpropanamido)-3-((S)-2-oxopyrrolidin-3-yl)propanoate 在 N-甲基吗啉 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以124 mg的产率得到methyl 2-{2-[3,4-(methylenedioxy)cinnamoyl]amino-1-oxo-3-phenyl}propyl-amino-3-(2-oxo-3-pyrrolidinyl)-propionate
  参考文献：
  名称：

  Design, synthesis, and evaluation of 3C protease inhibitors as anti-enterovirus 71 agents

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2008.06.015