(E)-(S)-4-[(S)-2-((S)-2-Benzyloxycarbonylamino-3-phenyl-propionylamino)-3-phenyl-propionylamino]-6-(trityl-carbamoyl)-hex-2-enoic acid ethyl ester | 1026488-94-7

• 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)-4-[(S)-2-((S)-2-Benzyloxycarbonylamino-3-phenyl-propionylamino)-3-phenyl-propionylamino]-6-(trityl-carbamoyl)-hex-2-enoic acid ethyl ester
• 英文别名: ethyl (E,4S)-7-oxo-4-[[(2S)-3-phenyl-2-[[(2S)-3-phenyl-2-(phenylmethoxycarbonylamino)propanoyl]amino]propanoyl]amino]-7-(tritylamino)hept-2-enoate
• CAS: 1026488-94-7
• 化学式: C₅₄H₅₄N₄O₇
• 分子量: 871.045
• InChiKey: ROFWRUUAWIFFLV-VLBJQXRJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.9
• 重原子数：
  65
• 可旋转键数：
  23
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  152
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (E)-(S)-4-[(S)-2-((S)-2-Benzyloxycarbonylamino-3-phenyl-propionylamino)-3-phenyl-propionylamino]-6-(trityl-carbamoyl)-hex-2-enoic acid ethyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (E)-(S)-4-[(S)-2-((S)-2-Benzyloxycarbonylamino-3-phenyl-propionylamino)-3-phenyl-propionylamino]-6-carbamoyl-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
• 作为产物：
  描述：

  ((S)-1-{(S)-1-[(S)-1-Hydroxymethyl-3-(trityl-carbamoyl)-propylcarbamoyl]-2-phenyl-ethylcarbamoyl}-2-phenyl-ethyl)-carbamic acid benzyl ester 在 2-碘酰基苯甲酸 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 生成 (E)-(S)-4-[(S)-2-((S)-2-Benzyloxycarbonylamino-3-phenyl-propionylamino)-3-phenyl-propionylamino]-6-(trityl-carbamoyl)-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