(4S)-N,N-dimethyl-4-(tert-butyloxycarbonylamino)-6-bromo-5-oxohexanamide | 193206-79-0

• 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: (4S)-N,N-dimethyl-4-(tert-butyloxycarbonylamino)-6-bromo-5-oxohexanamide
• 英文别名: tert-butyl N-[(3S)-1-bromo-6-(dimethylamino)-2,6-dioxohexan-3-yl]carbamate
• CAS: 193206-79-0
• 化学式: C₁₃H₂₃BrN₂O₄
• 分子量: 351.241
• InChiKey: DRZLPPQSVIJXQD-VIFPVBQESA-N

物化性质

• 熔点：
  59-60 °C
• 沸点：
  472.9±45.0 °C(Predicted)
• 密度：
  1.298±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  75.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4S)-N,N-dimethyl-4-(tert-butyloxycarbonylamino)-6-bromo-5-oxohexanamide 在 potassium fluoride 、 sodium azide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成
  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-((叔丁氧基羰基)氨基)-5-(二甲基氨基)-5-氧代戊酸 在 氢溴酸 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 为溶剂， 反应 2.08h， 生成 (4S)-N,N-dimethyl-4-(tert-butyloxycarbonylamino)-6-bromo-5-oxohexanamide
  参考文献：
  名称：

  肽基单氟甲基酮对甲型肝炎病毒3C蛋白酶的体外和离体抑制作用。

  摘要：

  甲型肝炎病毒（HAV）3C蛋白酶是负责处理病毒多蛋白的酶。尽管是半胱氨酸蛋白酶，但它表现出类似于哺乳动物丝氨酸蛋白酶的活性位点构型（Malcolm，BA Protein Science 1995，4，1439）。通过首先将前体N，N-二甲基谷氨酰胺氟甲基醇与三肽Ac-Leu-Ala-Ala-OH偶联，然后生成基于HAV 3C蛋白酶优选肽底物的肽基单氟甲基酮（peptidyl-FMK）。将产物氧化为相应的肽基-FMK（Ac-LAAQ'-FMK）。发现该分子是HAV 3C的不可逆灭活剂，其二级速率常数为3.3 x 10（2）M-1 s-1。19 F NMR光谱表明在氟甲基酮使酶失活时氟化物的置换。13C标记的抑制剂和HAV 3C蛋白酶之间的复合物的NMR光谱表明形成了（烷硫基）甲基酮。使用体外转录/翻译产生的各种底物进行的多蛋白加工研究表明，即使是最快速的蛋白水解事件，如2A-2B和2C-3A

  DOI：

  10.1016/s0968-0896(97)88649-x

文献信息

• In vitro and ex vivo inhibition of hepatitis A virus 3C proteinase by a peptidyl monofluoromethyl ketone
  作者：Tina S Morris、Sven Frormann、Shirley Shechosky、Christopher Lowe、Manjinder S Lall、Verena Gauss-Müller、Robert H Purcell、Suzanne U Emerson、John C Vederas、Bruce A Malcolm

  DOI：10.1016/s0968-0896(97)88649-x

  日期：1997.5

  configuration like those of the mammalian serine proteinases (Malcolm, B. A. Protein Science 1995, 4, 1439). A peptidyl monofluoromethyl ketone (peptidyl-FMK) based on the preferred peptide substrates for HAV 3C proteinase was generated by first coupling the precursor, N,N-dimethylglutamine fluoromethylalcohol, to the tripeptide, Ac-Leu-Ala-Ala-OH, and then oxidizing the product to the corresponding peptidyl-FMK

  甲型肝炎病毒（HAV）3C蛋白酶是负责处理病毒多蛋白的酶。尽管是半胱氨酸蛋白酶，但它表现出类似于哺乳动物丝氨酸蛋白酶的活性位点构型（Malcolm，BA Protein Science 1995，4，1439）。通过首先将前体N，N-二甲基谷氨酰胺氟甲基醇与三肽Ac-Leu-Ala-Ala-OH偶联，然后生成基于HAV 3C蛋白酶优选肽底物的肽基单氟甲基酮（peptidyl-FMK）。将产物氧化为相应的肽基-FMK（Ac-LAAQ'-FMK）。发现该分子是HAV 3C的不可逆灭活剂，其二级速率常数为3.3 x 10（2）M-1 s-1。19 F NMR光谱表明在氟甲基酮使酶失活时氟化物的置换。13C标记的抑制剂和HAV 3C蛋白酶之间的复合物的NMR光谱表明形成了（烷硫基）甲基酮。使用体外转录/翻译产生的各种底物进行的多蛋白加工研究表明，即使是最快速的蛋白水解事件，如2A-2B和2C-3A
• 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.
• 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.