3-[N¹,N²-bis(carbobenzyloxy)hydrazino]-N,N-dimethylpropanamide | 255873-55-3

• 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: 3-[N¹,N²-bis(carbobenzyloxy)hydrazino]-N,N-dimethylpropanamide
• 英文别名: benzyl N-[3-(dimethylamino)-3-oxopropyl]-N-(phenylmethoxycarbonylamino)carbamate
• CAS: 255873-55-3
• 化学式: C₂₁H₂₅N₃O₅
• 分子量: 399.447
• InChiKey: NIIANJYZEAEXNT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  88.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-[N¹,N²-bis(carbobenzyloxy)hydrazino]-N,N-dimethylpropanamide 在 palladium on activated charcoal 4-二甲氨基吡啶 、 氢气 、 三乙胺 作用下， 以 甲醇 、 氯仿 、 乙腈 为溶剂， 反应 7.0h， 生成 3-[N¹-phenoxycarbonylhydrazido][N²-(tert-butoxycarbonyl)hydrazino]-N,N-dimethylpropanamide
  参考文献：
  名称：

  Azodicarboxamides:  A New Class of Cysteine Proteinase Inhibitor for Hepatitis A Virus and Human Rhinovirus 3C Enzymes

  摘要：

  Hepatitis A virus (HAV) 3C and human rhinovirus (HRV) 3C cysteine proteinases have been shown to be essential for viral maturation and infectivity through the cleavage of a viral polyprotein precursor. A number of bis-hydrazides (e.g., 11-14), analogous to nanomolar inhibitors of cathepsin K, were synthesized and tested for effectiveness against HAV 3C and HRV 3C proteinases, but these compounds showed no significant inhibition of the viral enzymes. However, oxidation of the bis-hydrazides to the corresponding azodicarboxamides gave potent, irreversible inhibitors with IC50's in the low micromolar range. These compounds probably act. by adding the active site thiol to the azo moiety in a Michael fashion to give a covalent complex, which was detected by electrospray mass spectrometry. Azodicarboxamide 16 was shown to have a rate constant (k(inact)/k(I)) of 35 644 M-1 min(-1).

  DOI：

  10.1021/jo9915123
• 作为产物：
  描述：

  氯甲酸苄酯 、 3-hydrazino-N,N-(dimethyl)propanamide 在 sodium hydroxide 作用下， 以 乙醚 、 水 为溶剂， 反应 1.0h， 以5.91 g的产率得到3-[N¹,N²-bis(carbobenzyloxy)hydrazino]-N,N-dimethylpropanamide
  参考文献：
  名称：

  Azodicarboxamides:  A New Class of Cysteine Proteinase Inhibitor for Hepatitis A Virus and Human Rhinovirus 3C Enzymes

  摘要：

  Hepatitis A virus (HAV) 3C and human rhinovirus (HRV) 3C cysteine proteinases have been shown to be essential for viral maturation and infectivity through the cleavage of a viral polyprotein precursor. A number of bis-hydrazides (e.g., 11-14), analogous to nanomolar inhibitors of cathepsin K, were synthesized and tested for effectiveness against HAV 3C and HRV 3C proteinases, but these compounds showed no significant inhibition of the viral enzymes. However, oxidation of the bis-hydrazides to the corresponding azodicarboxamides gave potent, irreversible inhibitors with IC50's in the low micromolar range. These compounds probably act. by adding the active site thiol to the azo moiety in a Michael fashion to give a covalent complex, which was detected by electrospray mass spectrometry. Azodicarboxamide 16 was shown to have a rate constant (k(inact)/k(I)) of 35 644 M-1 min(-1).

  DOI：

  10.1021/jo9915123

文献信息

• Synthesis and testing of azaglutamine derivatives as inhibitors of Hepatitis A Virus (HAV) 3C proteinase
  作者：Y Huang

  DOI：10.1016/s0968-0896(99)00006-1

  日期：1999.4

  Hepatitis A virus (HAV) 3C proteinase is a picornaviral cysteine proteinase that is essential for cleavage of the initially synthesized viral polyprotein precursor to mature fragments and is therefore required for viral replication in vivo. Since the enzyme generally recognizes peptide substrates with L-glutamine at the P-1 site, four types of analogues having an azaglutamine residue were chemically synthesized: hydrazo-o-nitrophenylsulfenamides A (e.g. 16); frame-shifted hydrazo-o-nitrophenylsulfenamides B (e.g. 25-28); the azaglutamine sulfonamides C (e.g. 7, 8, 11, 12); and haloacetyl azaglutamine analogues 2 and 3. Testing of these compounds for inhibition of the HAV 3C proteinase employed a C24S mutant in which the non-essential surface cysteine was replaced with serine and which displays identical catalytic parameters to the wild-type enzyme. Sulfenamide 16 (type A) showed no significant inhibition. Sulfenamide 27 (type B) had an IC50 of ca 100 mu M and gave time-dependent inactivation of the enzyme due to disulfide bond formation with the active site cysteine thiol, as demonstrated by electrospray mass spectrometry. Sulfonamide 8 (type C) was a weak competitive inhibitor with an IC50 of approximately 75 mu M. The haloacetyl azaglutamine analogues 2 and 3 were time-dependent irreversible inactivators of HAV 3C proteinase with rate constants k(obs)[I] of 680 M-1 s(-1) and 870 M-1 s(-1), respectively, and were shown to alkylate the active site thiol. (C) 1999 Elsevier Science Ltd. All rights reserved.
• Azodicarboxamides:  A New Class of Cysteine Proteinase Inhibitor for Hepatitis A Virus and Human Rhinovirus 3C Enzymes
  作者：Richard D. Hill、John C. Vederas

  DOI：10.1021/jo9915123

  日期：1999.12.1

  Hepatitis A virus (HAV) 3C and human rhinovirus (HRV) 3C cysteine proteinases have been shown to be essential for viral maturation and infectivity through the cleavage of a viral polyprotein precursor. A number of bis-hydrazides (e.g., 11-14), analogous to nanomolar inhibitors of cathepsin K, were synthesized and tested for effectiveness against HAV 3C and HRV 3C proteinases, but these compounds showed no significant inhibition of the viral enzymes. However, oxidation of the bis-hydrazides to the corresponding azodicarboxamides gave potent, irreversible inhibitors with IC50's in the low micromolar range. These compounds probably act. by adding the active site thiol to the azo moiety in a Michael fashion to give a covalent complex, which was detected by electrospray mass spectrometry. Azodicarboxamide 16 was shown to have a rate constant (k(inact)/k(I)) of 35 644 M-1 min(-1).