tert-butyl N-[(2S)-3-oxo-1-[(3S)-2-oxopyrrolidin-3-yl]-4-(5,6,7,8-tetrafluoro-1,4-dioxo-3H-phthalazin-2-yl)butan-2-yl]carbamate | 741267-78-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: tert-butyl N-[(2S)-3-oxo-1-[(3S)-2-oxopyrrolidin-3-yl]-4-(5,6,7,8-tetrafluoro-1,4-dioxo-3H-phthalazin-2-yl)butan-2-yl]carbamate
• CAS: 741267-78-7
• 化学式: C₂₁H₂₂F₄N₄O₆
• 分子量: 502.422
• InChiKey: SEZITRLJPFYDIC-IUCAKERBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  134
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[(2S)-3-oxo-1-[(3S)-2-oxopyrrolidin-3-yl]-4-(5,6,7,8-tetrafluoro-1,4-dioxo-3H-phthalazin-2-yl)butan-2-yl]carbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以100%的产率得到2-[(S)-3-Amino-2-oxo-4-((S)-2-oxo-pyrrolidin-3-yl)-butyl]-5,6,7,8-tetrafluoro-2,3-dihydro-phthalazine-1,4-dione
  参考文献：
  名称：

  Structural variations in keto-glutamines for improved inhibition against hepatitis A virus 3C proteinase

  摘要：

  A series of keto-glutamine tetrapeptide analogs containing a 2-oxo-pyrrolidine ring as a glutamine side chain mimic were synthesized with both R and S configuration at the beta-carbon. Compounds bearing a phthalhydrazide moiety show improved reversible inhibition of HAV 3C proteinase in the low micromolar range. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.05.021
• 作为产物：
  描述：

  (S)-2-((tert-butoxycarbonyl)amino)-3-((S)-2-oxopyrrolidin-3-yl)propanoic acid 在 氢溴酸 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 生成 tert-butyl N-[(2S)-3-oxo-1-[(3S)-2-oxopyrrolidin-3-yl]-4-(5,6,7,8-tetrafluoro-1,4-dioxo-3H-phthalazin-2-yl)butan-2-yl]carbamate
  参考文献：
  名称：

  Structural variations in keto-glutamines for improved inhibition against hepatitis A virus 3C proteinase

  摘要：

  A series of keto-glutamine tetrapeptide analogs containing a 2-oxo-pyrrolidine ring as a glutamine side chain mimic were synthesized with both R and S configuration at the beta-carbon. Compounds bearing a phthalhydrazide moiety show improved reversible inhibition of HAV 3C proteinase in the low micromolar range. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.05.021

文献信息

• Synthesis and Evaluation of Keto-Glutamine Analogues as Potent Inhibitors of Severe Acute Respiratory Syndrome 3CL^pro
  作者：Rajendra P. Jain、Hanna I. Pettersson、Jianmin Zhang、Katherine D. Aull、Pascal D. Fortin、Carly Huitema、Lindsay D. Eltis、Jonathan C. Parrish、Michael N. G. James、David S. Wishart、John C. Vederas

  DOI：10.1021/jm0494873

  日期：2004.12.1

  The 3C-like proteinase (3CL(pro)) of severe acute respiratory syndrome (SARS) coronavirus is a key target for structure-based drug design against this viral infection. The enzyme recognizes peptide substrates with a glutamine residue at the P1 site. A series of keto-glutamine analogues with a phthalhydrazido group at the a-position were synthesized and tested as reversible inhibitiors against SARS 3CL(pro). Attachment of tripeptide (Ac-Val-Thr-Leu) to these glutamine-based "warheads" generated significantly better inhibitors (4a-c, 8a-d) with IC50 values ranging from 0.60 to 70 muM.
• Structural variations in keto-glutamines for improved inhibition against hepatitis A virus 3C proteinase
  作者：Rajendra P Jain、John C Vederas

  DOI：10.1016/j.bmcl.2004.05.021

  日期：2004.7

  A series of keto-glutamine tetrapeptide analogs containing a 2-oxo-pyrrolidine ring as a glutamine side chain mimic were synthesized with both R and S configuration at the beta-carbon. Compounds bearing a phthalhydrazide moiety show improved reversible inhibition of HAV 3C proteinase in the low micromolar range. (C) 2004 Elsevier Ltd. All rights reserved.