3-[5-methylisoxazol-3-yl]acrylic acid ethyl ester | 1065478-58-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 3-[5-methylisoxazol-3-yl]acrylic acid ethyl ester
• 英文别名: 3-[5-Methylisoxazol-3-yl]acrylic acid ethyl ester；ethyl (E)-3-(5-methyl-1,2-oxazol-3-yl)prop-2-enoate
• CAS: 1065478-58-1
• 化学式: C₉H₁₁NO₃
• 分子量: 181.191
• InChiKey: NEUIHVIMBYUVCG-SNAWJCMRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  52.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-[5-methylisoxazol-3-yl]acrylic acid ethyl ester 在 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 3-(5-methylisoxazol-3-yl)acrylic acid
  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：

  5-甲基异恶唑-3-甲醛 、 乙氧甲酰基亚甲基三苯基膦 以 甲苯 为溶剂， 反应 5.0h， 以81%的产率得到3-[5-methylisoxazol-3-yl]acrylic acid ethyl ester
  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

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.