(E)-(R)-5-(2-Amino-ethylamino)-4-[(S)-2-((S)-2-benzyloxycarbonylamino-4-methyl-pentanoylamino)-3-phenyl-propionylamino]-pent-2-enoic acid ethyl ester | 223526-73-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (E)-(R)-5-(2-Amino-ethylamino)-4-[(S)-2-((S)-2-benzyloxycarbonylamino-4-methyl-pentanoylamino)-3-phenyl-propionylamino]-pent-2-enoic acid ethyl ester
• CAS: 223526-73-6
• 化学式: C₃₂H₄₅N₅O₆
• 分子量: 595.739
• InChiKey: SBTKCYWQEQSDJS-KHBQZPANSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.21
• 重原子数：
  43.0
• 可旋转键数：
  18.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  160.88
• 氢给体数：
  5.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  N,N'-羰基二咪唑 、 (E)-(R)-5-(2-Amino-ethylamino)-4-[(S)-2-((S)-2-benzyloxycarbonylamino-4-methyl-pentanoylamino)-3-phenyl-propionylamino]-pent-2-enoic acid ethyl ester 以 四氢呋喃 为溶剂， 反应 3.5h， 以54%的产率得到(E)-(R)-4-[(S)-2-((S)-2-Benzyloxycarbonylamino-4-methyl-pentanoylamino)-3-phenyl-propionylamino]-5-(2-oxo-imidazolidin-1-yl)-pent-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. 4. Incorporation of P₁ Lactam Moieties as l-Glutamine Replacements

  摘要：

  The structure-based design, chemical synthesis, and biological evaluation of various human rhinovirus (HRV) 3C protease (3CP) inhibitors which incorporate P-1 lactam moieties in lieu of an L-glutamine residue are described. These compounds are comprised of a tripeptidyl or peptidomimetic binding determinant and an ethyl propenoate Michael acceptor moiety which forms an irreversible covalent adduct with the active site cysteine residue of the 3C enzyme. The P-1-lactam-containing inhibitors display significantly increased 3CP inhibition activity along with improved antirhinoviral properties relative to corresponding L-glutamine-derived molecules. In addition, several lactam-containing compounds exhibit excellent selectivity for HRV 3CP over several other serine and cysteine proteases and are not appreciably degraded by a variety of biological agents. One of the most potent inhibitors (AG7088, mean antirhinoviral EC90 0.10 approximate to mu M, n = 46 serotypes) is shown to warrant additional preclinical development to explore its potential for use as an antirhinoviral agent.

  DOI：

  10.1021/jm9805384
• 作为产物：
  描述：

  ethyl-3--E-propenoate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以92%的产率得到(E)-(R)-5-(2-Amino-ethylamino)-4-[(S)-2-((S)-2-benzyloxycarbonylamino-4-methyl-pentanoylamino)-3-phenyl-propionylamino]-pent-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. 4. Incorporation of P₁ Lactam Moieties as l-Glutamine Replacements

  摘要：

  The structure-based design, chemical synthesis, and biological evaluation of various human rhinovirus (HRV) 3C protease (3CP) inhibitors which incorporate P-1 lactam moieties in lieu of an L-glutamine residue are described. These compounds are comprised of a tripeptidyl or peptidomimetic binding determinant and an ethyl propenoate Michael acceptor moiety which forms an irreversible covalent adduct with the active site cysteine residue of the 3C enzyme. The P-1-lactam-containing inhibitors display significantly increased 3CP inhibition activity along with improved antirhinoviral properties relative to corresponding L-glutamine-derived molecules. In addition, several lactam-containing compounds exhibit excellent selectivity for HRV 3CP over several other serine and cysteine proteases and are not appreciably degraded by a variety of biological agents. One of the most potent inhibitors (AG7088, mean antirhinoviral EC90 0.10 approximate to mu M, n = 46 serotypes) is shown to warrant additional preclinical development to explore its potential for use as an antirhinoviral agent.

  DOI：

  10.1021/jm9805384