(E)-(S)-4-[(S)-2-((S)-2-Benzyloxycarbonylamino-4-methylsulfanyl-butyrylamino)-3-phenyl-propionylamino]-6-carbamoyl-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)-4-[(S)-2-((S)-2-Benzyloxycarbonylamino-4-methylsulfanyl-butyrylamino)-3-phenyl-propionylamino]-6-carbamoyl-hex-2-enoic acid ethyl ester
• 英文别名: ethyl (E,4S)-7-amino-4-[[(2S)-2-[[(2S)-2-(benzyloxycarbonylamino)-4-methylsulfanyl-butanoyl]amino]-3-phenyl-propanoyl]amino]-7-oxo-hept-2-enoate；ethyl (E,4S)-7-amino-4-[[(2S)-2-[[(2S)-4-methylsulfanyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]-3-phenylpropanoyl]amino]-7-oxohept-2-enoate
• 化学式: C₃₁H₄₀N₄O₇S
• 分子量: 612.747
• InChiKey: FPEBBDFGIGGORA-JWBCENJPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  43
• 可旋转键数：
  20
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  191
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (E)-(S)-4-[(S)-2-((S)-2-Benzyloxycarbonylamino-4-methylsulfanyl-butyrylamino)-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-4-methylsulfanyl-butyrylamino)-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