3-hydrazino-N,N-(dimethyl)propanamide | 107746-30-5

• 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-hydrazino-N,N-(dimethyl)propanamide
• 英文别名: β-hydrazino-N,N-dimethylpropionamide；3-hydrazinyl-N,N-dimethylpropanamide；3-hydrazino-N,N-dimethylpropanamide
• CAS: 107746-30-5
• 化学式: C₅H₁₃N₃O
• 分子量: 131.178
• InChiKey: RAXXJJMZIFXCJO-UHFFFAOYSA-N

物化性质

• 沸点：
  284.5±23.0 °C(Predicted)
• 密度：
  1.025±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  9
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  58.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-hydrazino-N,N-(dimethyl)propanamide 在 palladium on activated charcoal sodium hydroxide 、 氢气 、 氯甲酸乙酯 、 potassium carbonate 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 为溶剂， 反应 9.83h， 生成 3--N,N-(dimethyl)propanamide
  参考文献：
  名称：

  Synthesis and testing of azaglutamine derivatives as inhibitors of Hepatitis A Virus (HAV) 3C proteinase

  摘要：

  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.

  DOI：

  10.1016/s0968-0896(99)00006-1
• 作为产物：
  描述：

  N,N-二甲基丙烯酰胺 在 一水合肼 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以6.5 g的产率得到3-hydrazino-N,N-(dimethyl)propanamide
  参考文献：
  名称：

  Synthesis and testing of azaglutamine derivatives as inhibitors of Hepatitis A Virus (HAV) 3C proteinase

  摘要：

  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.

  DOI：

  10.1016/s0968-0896(99)00006-1
• 作为试剂：
  描述：

  methyl N-(2-chloropyridine-4-carbonyl)-N'-(2,2-difluoro-1,3-benzodioxol-5-yl)carbamimidothioate 、 3-hydrazino-N,N-(dimethyl)propanamide 在 3-hydrazino-N,N-(dimethyl)propanamide 作用下， 生成 3-[5-(2-chloropyridin-4-yl)-3-[(2,2-difluoro-1,3-benzodioxol-5-yl)amino]-1,2,4-triazol-1-yl]-N,N-dimethylpropanamide
  参考文献：
  名称：

  Trisubstituted 1,2,4-triazoles

  摘要：

  本发明涉及3-苯胺基-5-芳基三唑衍生物及其类似物或药学上可接受的盐，其制备过程，包含它们的药物组合物以及它们在治疗中的使用，根据式(I)。本发明特别涉及正向变构调制剂，其作用于尼古丁乙酰胆碱受体，这种正向变构调制剂具有增加尼古丁受体激动剂功效的能力。

  公开号：

  US08143419B2

文献信息

• [EN] TRISUBSTITUTED PYRAZOLES AS ACETYLCHOLINE RECEPTOR MODULATORS<br/>[FR] PYRAZOLES TRISUBSTITUÉS EN TANT QUE MODULATEURS DES RÉCEPTEURS DE L'ACÉTYLCHOLINE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2009135944A1

  公开（公告）日：2009-11-12

  The present invention relates to 1-alkyl-3-aniline-5-aryl-pyrazole derivatives and pharmaceutically acceptable salts thereof, processes for preparing them, pharmaceutical compositions containing them and their use in therapy, according to Formula (I). The invention particularly relates to positive allosteric modulators of nicotinic acetylcholine receptors, such positive allosteric modulator having the capability to increase the efficacy of nicotinic receptor agonists.

  本发明涉及1-烷基-3-苯胺基-5-芳基-吡唑衍生物及其药用盐，制备它们的方法，含有它们的药物组合物以及它们在治疗中的应用，根据式（I）。该发明特别涉及正向变构调节剂对尼古丁乙酰胆碱受体的作用，这种正向变构调节剂具有增加尼古丁受体激动剂效力的能力。
• Process for production of 2-pyrazolin-5-ones
  申请人：Nissan Chemical Industries, Ltd.

  公开号：US04931565A1

  公开（公告）日：1990-06-05

  A process for production of 2-pyrazolin-5-ones having the formula (I): ##STR1## which comprises cyclizing hydrazone derivatives having the formula (II): ##STR2## in the presence of a base; wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 each represents a specific group; compounds having the formula (I) as well as compounds having the formula (II) and a process for production thereof.

  生产具有化学式(I)的2-吡唑啉-5-酮的方法：在碱存在下，使具有化学式(II)的腙酮衍生物环化；其中R.sup.1、R.sup.2、R.sup.3和R.sup.4分别代表特定基团；具有化学式(I)的化合物以及具有化学式(II)的化合物及其生产方法。
• TRISUBSTITUTED PYRAZOLES AS ACETYLCHOLINE RECEPTOR MODULATORS
  申请人：Thuring Johannes Wilhelmus John F.

  公开号：US20110065683A1

  公开（公告）日：2011-03-17

  The present invention relates to 1-alkyl-3-aniline-5-aryl-pyrazole derivatives and pharmaceutically acceptable salts thereof, processes for preparing them, pharmaceutical compositions containing them and their use in therapy, according to Formula (I). The invention particularly relates to positive allosteric modulators of nicotinic acetylcholine receptors, such positive allosteric modulator having the capability to increase the efficacy of nicotinic receptor agonists.

  本发明涉及1-烷基-3-苯胺-5-芳基吡唑衍生物及其药学上可接受的盐、制备它们的过程、含有它们的制药组合物以及它们在治疗中的应用，根据式（I）。本发明特别涉及正向变构调节剂，其具有增加烟碱乙酰胆碱受体激动剂效力的能力。
• Trisubstituted pyrazoles as acetylcholine receptor modulators
  申请人：Thuring Johannes Wilhelmus John F.

  公开号：US08779158B2

  公开（公告）日：2014-07-15

  The present invention relates to 1-alkyl-3-aniline-5-aryl-pyrazole derivatives and pharmaceutically acceptable salts thereof, processes for preparing them, pharmaceutical compositions containing them and their use in therapy, according to Formula (I). The invention particularly relates to positive allosteric modulators of nicotinic acetylcholine receptors, such positive allosteric modulator having the capability to increase the efficacy of nicotinic receptor agonists.

  本发明涉及1-烷基-3-苯胺-5-芳基-吡唑衍生物及其药学上可接受的盐，制备它们的方法，包含它们的制药组合物以及它们在治疗中的应用，根据式（I）。本发明特别涉及正向变构调节剂，其具有增加尼古丁乙酰胆碱受体激动剂的功效的能力。
• 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).