(alphaR)-alpha-[(3S)-3-(叔-丁基氧羰基氨基)-4-甲基-2-氧代戊基]-4-氟-苯丙酸2-丙烯-1-基酯 | 862414-82-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (alphaR)-alpha-[(3S)-3-(叔-丁基氧羰基氨基)-4-甲基-2-氧代戊基]-4-氟-苯丙酸2-丙烯-1-基酯
• 英文名称: allyl (2R,5S)-5-(tert-butoxycarbonyl)amino-2-(4-fluorobenzyl)-6-methyl-4-oxoheptanoate
• 英文别名: prop-2-enyl (2R,5S)-2-[(4-fluorophenyl)methyl]-6-methyl-5-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxoheptanoate
• CAS: 862414-82-2
• 化学式: C₂₃H₃₂FNO₅
• 分子量: 421.509
• InChiKey: HCCFXTUGPNCBLL-XLIONFOSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  30
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (alphaR)-alpha-[(3S)-3-(叔-丁基氧羰基氨基)-4-甲基-2-氧代戊基]-4-氟-苯丙酸2-丙烯-1-基酯 在 N-甲基吗啉 、 盐酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 allyl (2R,5S)-2-(4-fluorobenzyl)-6-methyl-5-{[(5-methyl-3-isoxazolyl)carbonyl]amino}-4-oxoheptanoate
  参考文献：
  名称：

  Inhibition of the severe acute respiratory syndrome 3CL protease by peptidomimetic α,β-unsaturated esters

  摘要：

  The proteolytic processing of polyproteins by the 3CL protease of severe acute respiratory syndrome coronavirus is essential for the viral propagation. A series of tripeptide alpha,beta-unsaturated esters and ketomethylene isosteres, including AG7088, are synthesized and assayed to target the 3CL protease. Though AG7088 is inactive (IC50 > 100 mu M), the ketomethylene isosteres and tripeptide alpha,beta-unsaturated esters containing both P1 and P2 phenylalanine residues show modest inhibitory activity (IC50 = 11-39 mu M). The Phe-Phe dipeptide inhibitors 18a-e are designed on the basis of computer modeling of the enzyme-inhibitor complex. The most potent inhibitor 18c with an inhibition constant of 0.52 mu M is obtained by condensation of the Phe-Phe dipeptide alpha,beta-unsaturated ester with 4-(dimethylamino)cinnamic acid. The cell-based assays also indicate that 18c is a nontoxic anti-SARS agent with an EC50 value of 0.18 mu M. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.05.065
• 作为产物：
  描述：

  (3R)-1-tert-butyl 4-methyl 2-((S)-2-(benzyloxycarbonylamino)-3-methylbutanoyl)-3-(4-fluorobenzyl)succinate 在 palladium on activated charcoal lithium hydroxide 、 氢气 、 caesium carbonate 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 42.0h， 生成 (alphaR)-alpha-[(3S)-3-(叔-丁基氧羰基氨基)-4-甲基-2-氧代戊基]-4-氟-苯丙酸2-丙烯-1-基酯
  参考文献：
  名称：

  Inhibition of the severe acute respiratory syndrome 3CL protease by peptidomimetic α,β-unsaturated esters

  摘要：

  The proteolytic processing of polyproteins by the 3CL protease of severe acute respiratory syndrome coronavirus is essential for the viral propagation. A series of tripeptide alpha,beta-unsaturated esters and ketomethylene isosteres, including AG7088, are synthesized and assayed to target the 3CL protease. Though AG7088 is inactive (IC50 > 100 mu M), the ketomethylene isosteres and tripeptide alpha,beta-unsaturated esters containing both P1 and P2 phenylalanine residues show modest inhibitory activity (IC50 = 11-39 mu M). The Phe-Phe dipeptide inhibitors 18a-e are designed on the basis of computer modeling of the enzyme-inhibitor complex. The most potent inhibitor 18c with an inhibition constant of 0.52 mu M is obtained by condensation of the Phe-Phe dipeptide alpha,beta-unsaturated ester with 4-(dimethylamino)cinnamic acid. The cell-based assays also indicate that 18c is a nontoxic anti-SARS agent with an EC50 value of 0.18 mu M. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.05.065