3-(p-methylphenylsulfonylamino)-N,N-(dimethyl)propanamide | 193635-15-3

• 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-(p-methylphenylsulfonylamino)-N,N-(dimethyl)propanamide
• 英文别名: N,N-dimethyl-3-[(4-methylphenyl)sulfonylamino]propanamide
• CAS: 193635-15-3
• 化学式: C₁₂H₁₈N₂O₃S
• 分子量: 270.353
• InChiKey: GBSSSDPUPKZQMZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  74.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(p-methylphenylsulfonylamino)-N,N-(dimethyl)propanamide 在 palladium on activated charcoal 盐酸 、 氢气 、 sodium hydride 作用下， 以 甲醇 为溶剂， 反应 1.5h， 生成 (3S)-1-<3'-(N,N-dimethylamino)-3'-oxopropyl>-N¹-(p-methylphenylsulfonyl)>-1,3-diaminobutan-2-one hydrochloride
  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-dimethyl 1-(p-tolylsulfonyl)aziridine-2-carboxamide 在 N,N-二甲基乙醇胺 、 samarium diiodide 作用下， 以 四氢呋喃 为溶剂， 反应 0.08h， 以86%的产率得到3-(p-methylphenylsulfonylamino)-N,N-(dimethyl)propanamide
  参考文献：
  名称：

  Reduction of 2-Acylaziridines by Samarium(II) Iodide. An Efficient and Regioselective Route to β-Amino Carbonyl Compounds.

  摘要：

  DOI：

  10.1016/s0040-4020(97)00576-0

文献信息

• Kinetic, Thermodynamic, and Dynamic Control in Normal vs. Cross [2 + 2] Cycloadditions of Ene-Keteniminium Ions: Computational Understanding, Prediction, and Experimental Verification
  作者：Pan Zhang、Zhi-Xiang Yu

  DOI：10.1021/jacs.3c00685

  日期：2023.5.3

  Almost all reported intramolecular [2 + 2] reactions of ene-keteniminium ions gave normal [2 + 2] products with a fused bicycle framework, but not cross [2 + 2] products with a bicyclo[3.1.1]heptane skeleton, a highly pursued bioisostere in pharmaceutical chemistry. How to rationalize this and design new cross [2 + 2] reactions? Theoretical studies using density functional theory, high-level ab initio

  几乎所有报道的烯-烯酮亚胺离子的分子内 [2 + 2] 反应都会产生具有稠合自行车骨架的正常 [2 + 2] 产物，但不会产生具有双环 [3.1.1] 庚烷骨架的交叉 [2 + 2] 产物，a药物化学中高度追求的生物电子等排体。如何合理化并设计新的交叉 [2 + 2] 反应？使用密度泛函理论、高水平从头算单点能量计算和分子动力学的理论研究表明，这种 [2 + 2] 反应具有所有三种区域化学控制模式：反应受动力学、热力学或动态控制。形成内切和外切的碳阳离子模型已提出碳正离子以使反应结果合理化，揭示了链（烯烃和烯酮亚胺离子之间）、取代基（在烯烃上）和烯-烯酮亚胺离子中的烯烃构型起着关键作用。这些认识进一步用于预测在具有反式的烯烃的末端位置引入取代基烯-烯酮亚胺离子中的构型可以实现交叉[2+2]反应，该反应对烷基取代基是动态控制的，对芳基取代基是动力学控制的。这些和更多其他预测都通过实验实现了，并且可以实现许多具有双环[3
• Reduction of 2-Acylaziridines by Samarium(II) Iodide. An Efficient and Regioselective Route to β-Amino Carbonyl Compounds.
  作者：G Molander

  DOI：10.1016/s0040-4020(97)00576-0

  日期：1997.6.30
• 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.