tert-butyl (2S)-2-[3-(dimethylamino)-3-oxo-propyl]-3-oxo-azetidine-1-carboxylate | 387338-21-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环丁烷
• 英文名称: tert-butyl (2S)-2-[3-(dimethylamino)-3-oxo-propyl]-3-oxo-azetidine-1-carboxylate
• 英文别名: tert-butyl (2S)-2-[3-(dimethylamino)-3-oxopropyl]-3-oxoazetidine-1-carboxylate
• CAS: 387338-21-8
• 化学式: C₁₃H₂₂N₂O₄
• 分子量: 270.329
• InChiKey: YDXUGSRRVMVTMV-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  66.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (2S)-2-[3-(dimethylamino)-3-oxo-propyl]-3-oxo-azetidine-1-carboxylate 在 sodium tetrahydroborate 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 5.5h， 生成 (2S)-2-(N,N-dimethylpropanamid-3-yl)-3-hydroxyazetidine trifluoroacetate salt
  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
• 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 dirhodium tetraacetate 、 氯甲酸乙酯 、 三乙胺 作用下， 以 四氢呋喃 、 苯 为溶剂， 反应 7.5h， 生成 tert-butyl (2S)-2-[3-(dimethylamino)-3-oxo-propyl]-3-oxo-azetidine-1-carboxylate
  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

文献信息

• Synthesis and Evaluation of Keto-Glutamine Analogues as Inhibitors of Hepatitis A Virus 3C Proteinase
  作者：Yeeman K. Ramtohul、Michael N. G. James、John C. Vederas

  DOI：10.1021/jo0157831

  日期：2002.5.1

  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.