(E)-(S)-6-Carbamoyl-4-[(S)-2-((S)-2-ethylsulfanylcarbonylamino-4-methyl-pentanoylamino)-3-phenyl-propionylamino]-hex-2-enoic acid ethyl ester

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (E)-(S)-6-Carbamoyl-4-[(S)-2-((S)-2-ethylsulfanylcarbonylamino-4-methyl-pentanoylamino)-3-phenyl-propionylamino]-hex-2-enoic acid ethyl ester
• 英文别名: 6-Carbamoyl-4-[2-(2-ethylsulfanylcarbonylamino-4-methyl-pentanoylamino)-3-phenyl-propionylamino]-hex-2-enoic acid, ethyl ester；ethyl (E,4S)-7-amino-4-[[(2S)-2-[[(2S)-2-(ethylsulfanylcarbonylamino)-4-methylpentanoyl]amino]-3-phenylpropanoyl]amino]-7-oxohept-2-enoate
• 化学式: C₂₇H₄₀N₄O₆S
• 分子量: 548.704
• InChiKey: QMZHSGPRTLCOGB-JKCGXOLOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  38
• 可旋转键数：
  18
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  182
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (E)-(S)-4-[(S)-2-((S)-2-Ethylsulfanylcarbonylamino-4-methyl-pentanoylamino)-3-phenyl-propionylamino]-6-(trityl-carbamoyl)-hex-2-enoic acid ethyl ester 在 三氟乙酸 作用下， 以 四氢呋喃 为溶剂， 生成 (E)-(S)-6-Carbamoyl-4-[(S)-2-((S)-2-ethylsulfanylcarbonylamino-4-methyl-pentanoylamino)-3-phenyl-propionylamino]-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. 2. Peptide Structure−Activity Studies

  摘要：

  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.

  DOI：

  10.1021/jm9800696

文献信息

• 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.