ethyl (E,4S)-4-[[(2S)-3-(4-cyanophenyl)-2-[[(2S)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]propanoyl]amino]-7-oxo-7-(tritylamino)hept-2-enoate | 211186-13-9

• 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: ethyl (E,4S)-4-[[(2S)-3-(4-cyanophenyl)-2-[[(2S)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]propanoyl]amino]-7-oxo-7-(tritylamino)hept-2-enoate
• CAS: 211186-13-9
• 化学式: C₅₂H₅₅N₅O₇
• 分子量: 862.038
• InChiKey: BRHXGABAPYHLGD-KZRGINSGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.4
• 重原子数：
  64
• 可旋转键数：
  23
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  176
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl (E,4S)-4-[[(2S)-3-(4-cyanophenyl)-2-[[(2S)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]propanoyl]amino]-7-oxo-7-(tritylamino)hept-2-enoate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 以71%的产率得到ethyl (E,4S)-7-amino-4-[[(2S)-2-[[(2S)-2-(benzyloxycarbonylamino)-4-methyl-pentanoyl]amino]-3-(4-cyanophenyl)propanoyl]amino]-7-oxo-hept-2-enoate
  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：

  Boc-Phe(4-I)-Gln(Trt)(Trt)-ol 在 盐酸 、 四(三苯基膦)钯 、 三乙胺 、 2-碘酰基苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 1.58h， 生成 ethyl (E,4S)-4-[[(2S)-3-(4-cyanophenyl)-2-[[(2S)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]propanoyl]amino]-7-oxo-7-(tritylamino)hept-2-enoate
  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