ethyl-3--E-propenoate | 199005-72-6

• 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: ethyl-3--E-propenoate
• 英文别名: ethyl (E,4R)-4-[[(2S)-2-[[(2S)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-3-phenylpropanoyl]amino]-5-[(2-methylpropan-2-yl)oxycarbonylamino]pent-2-enoate
• CAS: 199005-72-6
• 化学式: C₃₅H₄₈N₄O₈
• 分子量: 652.788
• InChiKey: DUAKKUJUWPZSNV-CMAMQRGNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  47
• 可旋转键数：
  20
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  161
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl-3--E-propenoate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 以73%的产率得到(E)-(R)-5-Amino-4-[(S)-2-((S)-2-benzyloxycarbonylamino-4-methyl-pentanoylamino)-3-phenyl-propionylamino]-pent-2-enoic acid ethyl ester; hydrochloride
  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：

  乙氧甲酰基亚甲基三苯基膦 、 {(S)-1-[(S)-1-((S)-2-tert-Butoxycarbonylamino-1-formyl-ethylcarbamoyl)-2-phenyl-ethylcarbamoyl]-3-methyl-butyl}-carbamic acid benzyl ester 以 四氢呋喃 为溶剂， 生成 ethyl-3--E-propenoate
  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.
• Structure-Based Design, Synthesis, and Biological Evaluation of Irreversible Human Rhinovirus 3C Protease Inhibitors. 4. Incorporation of P₁ Lactam Moieties as <scp>l</scp>-Glutamine Replacements
  作者：Peter S. Dragovich、Thomas J. Prins、Ru Zhou、Stephen E. Webber、Joseph T. Marakovits、Shella A. Fuhrman、Amy K. Patick、David A. Matthews、Caroline A. Lee、Clifford E. Ford、Benjamin J. Burke、Paul A. Rejto、Thomas F. Hendrickson、Tove Tuntland、Edward L. Brown、James W. Meador、Rose Ann Ferre、James E. V. Harr、Maha B. Kosa、Stephen T. Worland

  DOI：10.1021/jm9805384

  日期：1999.4.1

  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.