(E)-(S)-4-((E)-3-Benzo[1,3]dioxol-5-yl-acryloylamino)-5-((S)-2-oxo-pyrrolidin-3-yl)-pent-2-enoic acid ethyl ester

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-(S)-4-((E)-3-Benzo[1,3]dioxol-5-yl-acryloylamino)-5-((S)-2-oxo-pyrrolidin-3-yl)-pent-2-enoic acid ethyl ester
• 英文别名: ethyl (E,4S)-4-[[(E)-3-(1,3-benzodioxol-5-yl)prop-2-enoyl]amino]-5-[(3S)-2-oxopyrrolidin-3-yl]pent-2-enoate
• 化学式: C₂₁H₂₄N₂O₆
• 分子量: 400.431
• InChiKey: SVRKNEXEKCRGPU-ZNKHKNALSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  6

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 (E)-(S)-4-((E)-3-Benzo[1,3]dioxol-5-yl-acryloylamino)-5-((S)-2-oxo-pyrrolidin-3-yl)-pent-2-enoic acid ethyl ester
  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

• Antipicornaviral compounds and compositions, their pharmaceutical uses, and materials for their synthesis
  申请人：——

  公开号：US20020061916A1

  公开（公告）日：2002-05-23

  Compounds of the formula: 1 where the formula variables are as defined in the disclosure, advantageously inhibit or block the biological activity of the picornaviral 3C protease. These compounds, as well as pharmaceutical compositions containing these compounds, are useful for treating patients or hosts infected with one or more picornaviruses, such as RVP. Intermediates and synthetic methods for preparing such compounds are also described.

  公式为1的化合物，其中公式变量如披露所定义，有利地抑制或阻断了小肠病毒3C蛋白酶的生物活性。这些化合物以及含有这些化合物的制药组合物，对于治疗感染了一个或多个小肠病毒（如RVP）的患者或宿主是有用的。还描述了制备这些化合物的中间体和合成方法。
• ANTIPICORNAVIRAL COMPOUNDS AND COMPOSITIONS, THEIR PHARMACEUTICAL USES, AND MATERIALS FOR THEIR SYNTHESIS
  申请人：AGOURON PHARMACEUTICALS, INC.

  公开号：EP1355878A2

  公开（公告）日：2003-10-29
• US6632825B2
  申请人：——

  公开号：US6632825B2

  公开（公告）日：2003-10-14
• US6989384B2
  申请人：——

  公开号：US6989384B2

  公开（公告）日：2006-01-24
• [EN] ANTIPICORNAVIRAL COMPOUNDS AND COMPOSITIONS, THEIR PHARMACEUTICAL USES, AND MATERIALS FOR THEIR SYNTHESIS<br/>[FR] COMPOSES ET COMPOSITIONS ANTIPICORNAVIRAUX, LEURS APPLICATIONS PHARMACEUTIQUES ET MATIERES UTILES A LA SYNTHESE DE CEUX-CI
  申请人：AGOURON PHARMA

  公开号：WO2001096297A2

  公开（公告）日：2001-12-20

  Compounds of the formula (I), where the formula variables are as defined in the disclosure, advantageously inhibit or block the biological activity of the picornaviral 3C protease. These compounds, as well as pharmaceutical compositions containing these compounds, are useful for treating patients or hosts infected with one or more picornaviruses, such as RVP. Intermediates and synthetic methods for preparing such compounds are also described.