trans-(4S)-4-Amino-6-(tritylcarbamoyl)hex-2-enoic Acid Ethyl Ester | 343566-87-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: trans-(4S)-4-Amino-6-(tritylcarbamoyl)hex-2-enoic Acid Ethyl Ester
• 英文别名: ethyl (E,4S)-4-amino-7-oxo-7-(tritylamino)hept-2-enoate
• CAS: 343566-87-0
• 化学式: C₂₈H₃₀N₂O₃
• 分子量: 442.558
• InChiKey: RRMGTQSDPBOAIV-NFRPBIJRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  33
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  81.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  trans-(4S)-4-Amino-6-(tritylcarbamoyl)hex-2-enoic Acid Ethyl Ester 在 N-甲基吗啉 、 盐酸 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 19.0h， 生成 (E)-(S)-4-((S)-2-Amino-3-phenyl-propionylamino)-6-(trityl-carbamoyl)-hex-2-enoic acid ethyl ester
  参考文献：
  名称：

  Structure-based design of irreversible, tripeptidyl human rhinovirus 3C protease inhibitors containing N-methyl amino acids

  摘要：

  Tripeptide-derived molecules incorporating N-methyl amino acid residues and C-terminal Michael acceptor moieties were evaluated as irreversible inhibitors of the cysteine-containing human rhinovirus 3C protease (3CP). Such compounds displayed good 3CP inhibition activity (k(obs)/[I] up to 610,000 M(-1)s(-1)) and potent in vitro antiviral properties (EC50 approaching 0.03 mu M) when tested against HRV serotype-14. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00368-6
• 作为产物：
  描述：

  N-Boc-N'-三苯甲基-L-谷氨酰胺 在 N-甲基吗啉 、 盐酸 、 sodium hexamethyldisilazane 、 二异丁基氢化铝 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 甲苯 为溶剂， 反应 12.16h， 生成 trans-(4S)-4-Amino-6-(tritylcarbamoyl)hex-2-enoic Acid Ethyl Ester
  参考文献：
  名称：

  Structure-Based Design, Synthesis, and Biological Evaluation of Irreversible Human Rhinovirus 3C Protease Inhibitors. 1. Michael Acceptor Structure−Activity Studies

  摘要：

  The structure-based design, chemical synthesis, and biological evaluation of peptide-derived human rhinovirus (HRV) 3C protease (3CP) inhibitors are described. These compounds incorporate various Michael acceptor moieties and are shown to irreversibly bind to HRV serotype 14 3CP with inhibition activities (k(obs)/[I]) ranging from 100 to 600 000 M-1 s(-1). These inhibitors are also shown to exhibit antiviral activity when tested against HRV-14-infected H1-HeLa cells with EC50's approaching 0.50 mu M. Extensive structure-activity relationships developed by Michael acceptor alteration are reported along with the evaluation of several compounds against HRV serotypes other than 14. A 2.0 Angstrom crystal structure of a peptide-derived inhibitor complexed with HRV-2 3CP is also detailed.

  DOI：

  10.1021/jm980068d

文献信息

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

  公开号：US20010047006A1

  公开（公告）日：2001-11-29

  Compounds of the formula: 1 where the formula variables are as defined herein, are disclosed that advantageously inhibit or block the biological activity of the picornaviral 3C protease. Also disclosed are compounds of the formula: 2 where the formula variables are as defined herein that 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 rhinovirus 3C proteases. Intermediates and synthetic methods for preparing such compounds are also described.

  披露了具有以下公式的化合物： 1 其中公式变量如本文所述定义，这些化合物能够有优势地抑制或阻断小RNA病毒3C蛋白酶的生物学活性。还披露了具有以下公式的化合物： 2 其中公式变量如本文所述定义，这些化合物能够有优势地抑制或阻断小RNA病毒3C蛋白酶的生物学活性。这些化合物以及含有这些化合物的药物组合物对于治疗感染了一种或多种小RNA病毒的患者或宿主是有用的，例如鼻病毒3C蛋白酶。还描述了用于制备这些化合物的中间体和合成方法。
• [EN] ANTIPICORNAVIRAL COMPOUNDS AND COMPOSITIONS, THEIR PHARMACEUTICAL USES, AND MATERIALS FOR THEIR SYNTHESIS<br/>[FR] COMPOSES ET COMPOSITIONS ANTI-PICORNAVIRUS; UTILISATIONS PHARMACEUTIQUES ET MATERIAUX EMPLOYES POUR LEUR SYNTHESE
  申请人：AGOURON PHARMA

  公开号：WO2001040189A1

  公开（公告）日：2001-06-07

  Compounds of formula (I), where the formula variables are as defined herein, are disclosed that advantageously inhibit or block the biological activity of the picornaviral 3C protease. Also disclosed are compounds of formula (II) where the formula variables are as defined herein that 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 rhinovirus 3C proteases. Intermediates and synthetic methods for preparing such compounds are also described.

  本发明披露了式(I)的化合物，其中式变量如本文所定义，这些化合物有利地抑制或阻断了小肠病毒3C蛋白酶的生物活性。本发明还披露了式(II)的化合物，其中式变量如本文所定义，这些化合物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药物组合物，对于治疗感染一种或多种小肠病毒（如鼻病毒3C蛋白酶）的患者或宿主非常有用。还描述了制备这些化合物的中间体和合成方法。
• Structure-Based Design, Synthesis, and Biological Evaluation of Irreversible Human Rhinovirus 3C Protease Inhibitors. 2. Peptide Structure−Activity Studies
  作者：Peter S. Dragovich、Stephen E. Webber、Robert E. Babine、Shella A. Fuhrman、Amy K. Patick、David A. Matthews、Siegfried H. Reich、Joseph T. Marakovits、Thomas J. Prins、Ru Zhou、Jayashree Tikhe、Ethel S. Littlefield、Ted M. Bleckman、Michael B. Wallace、Thomas L. Little、Clifford E. Ford、James W. Meador、Rose Ann Ferre、Edward L. Brown、Susan L. Binford、Dorothy M. DeLisle、Stephen T. Worland

  DOI：10.1021/jm9800696

  日期：1998.7.1

  The structure-based design, chemical synthesis, and biological evaluation of various peptide-derived human rhinovirus (HRV) 3C protease (3CP) inhibitors are described. These compounds are comprised of an ethyl propenoate Michael acceptor moiety and a tripeptidyl binding determinant. The systematic modification of each amino acid residue present in the binding determinant as well as the N-terminal functionality is described. Such modifications are shown to provide irreversible HRV-14 3CP inhibitors with anti-3CP activities (k(obs)/[I]) ranging from 60 to 280 000 M-1 s(-1) and antiviral EC50's which approach 0.15 mu M. An optimized inhibitor which incorporates several improvements identified by the structure-activity studies is also described. This molecule displays very rapid irreversible inhibition of HRV-14 3CP (k(obs)/[I] = 800 000 M-1 s(-1)) and potent antiviral activity against HRV-14 in cell culture (EC50 = 0.056 mu M). A 1.9 Angstrom crystal structure of an S-alkylthiocarbamate-containing inhibitor complexed with HRV-8 3CP is also detailed.
• ANTIPICORNAVIRAL COMPOUNDS AND COMPOSITIONS, THEIR PHARMACEUTICAL USES, AND MATERIALS FOR THEIR SYNTHESIS
  申请人：AGOURON PHARMACEUTICALS, INC.

  公开号：EP1252145A1

  公开（公告）日：2002-10-30
• US6514997B2
  申请人：——

  公开号：US6514997B2

  公开（公告）日：2003-02-04