tert-butyl N-[(1S)-4-(dimethylamino)-1-[2-(5-nitro-1,4-dioxo-3H-phthalazin-2-yl)acetyl]-4-oxo-butyl]carbamate | 387338-16-1

• 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: tert-butyl N-[(1S)-4-(dimethylamino)-1-[2-(5-nitro-1,4-dioxo-3H-phthalazin-2-yl)acetyl]-4-oxo-butyl]carbamate
• 英文别名: tert-butyl N-[(3S)-6-(dimethylamino)-1-(5-nitro-1,4-dioxo-3H-phthalazin-2-yl)-2,6-dioxohexan-3-yl]carbamate
• CAS: 387338-16-1
• 化学式: C₂₁H₂₇N₅O₈
• 分子量: 477.474
• InChiKey: XMXUBCZIWRLIIU-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  171
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  三氟乙酸 、 tert-butyl N-[(1S)-4-(dimethylamino)-1-[2-(5-nitro-1,4-dioxo-3H-phthalazin-2-yl)acetyl]-4-oxo-butyl]carbamate 以 二氯甲烷 为溶剂， 反应 1.5h， 生成 (S)-4-Amino-6-(5-nitro-1,4-dioxo-3,4-dihydro-1H-phthalazin-2-yl)-5-oxo-hexanoic acid dimethylamide; compound with trifluoro-acetic acid
  参考文献：
  名称：

  Synthesis and Evaluation of Keto-Glutamine Analogues as Potent Inhibitors of Severe Acute Respiratory Syndrome 3CL^pro

  摘要：

  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.

  DOI：

  10.1021/jm0494873
• 作为产物：
  描述：

  (S)-2-((叔丁氧基羰基)氨基)-5-(二甲基氨基)-5-氧代戊酸 在 氢溴酸 、 氯甲酸乙酯 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.5h， 生成 tert-butyl N-[(1S)-4-(dimethylamino)-1-[2-(5-nitro-1,4-dioxo-3H-phthalazin-2-yl)acetyl]-4-oxo-butyl]carbamate
  参考文献：
  名称：

  Synthesis and Evaluation of Keto-Glutamine Analogues as Inhibitors of Hepatitis A Virus 3C Proteinase

  摘要：

  Hepatitis A virus (HAV) 3C enzyme is a picornaviral cysteine proteinase involved in the processing of the initially synthesized viral polyprotein and is therefore important for viral maturation and infectivity, Although it is a cysteine proteinase, this enzyme has a topology similar to those of the chymotrypsin-like serine proteinases. Since the enzyme recognizes peptide substrates with a glutamine residue at the P, site, a number of ketone-containing glutamine compounds analogous to nanomolar inhibitors of cathepsin K were synthesized and tested for inhibition against HAV 3C proteinase. In addition, a 3-azetidinone scaffold was incorporated into the glutamine fragment but gave only modest inhibition. However, introduction of a phthalhydrazido group a to the ketone moiety gave significantly better inhibitors with IC50 values ranging from 13 to 164 muM, presumably due to the effect of intramolecular hydrogen bonding to the ketone. In addition, the tetrapeptide phthalhydrazide 24 was found to be a competitive reversible inhibitor (K-i = 9 x 10(-6) M) and also showed no loss of inhibitory potency in the presence of dithiothreitol.

  DOI：

  10.1021/jo0157831