Ethyl 4-(4-aminophenyl)-2,4-dioxobutanoate | 1027104-63-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Ethyl 4-(4-aminophenyl)-2,4-dioxobutanoate
• CAS: 1027104-63-7
• 化学式: C₁₂H₁₃NO₄
• 分子量: 235.24
• InChiKey: CSKIYDVXJUBRCR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  86.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Ethyl 4-(4-aminophenyl)-2,4-dioxobutanoate 在 lithium hydroxide 作用下， 以 乙醇 为溶剂， 反应 0.67h， 生成 5-(4-Aminophenyl)-1-(3,4-dichlorophenyl)pyrazole-3-carboxylic acid
  参考文献：
  名称：

  Diphenylpyrazoles as Replication Protein A Inhibitors

  摘要：

  Replication Protein A is the primary eukaryotic ssDNA binding protein that has a central role in initiating the cellular response to DNA damage. RPA recruits multiple proteins to sites of DNA damage via the N-terminal domain of the 70 kDa subunit (RPA70N). Here we describe the optimization of a diphenylpyrazole carboxylic acid series of inhibitors of these RPA-protein interactions. We evaluated substituents on the aromatic rings as well as the type and geometry of the linkers used to combine fragments, ultimately leading to submicromolar inhibitors of RPA70N protein-protein interactions.

  DOI：

  10.1021/ml5003629
• 作为产物：
  描述：

  4-氨基苯乙酮 、 草酸二乙酯 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 0.33h， 生成 Ethyl 4-(4-aminophenyl)-2,4-dioxobutanoate
  参考文献：
  名称：

  Diphenylpyrazoles as Replication Protein A Inhibitors

  摘要：

  Replication Protein A is the primary eukaryotic ssDNA binding protein that has a central role in initiating the cellular response to DNA damage. RPA recruits multiple proteins to sites of DNA damage via the N-terminal domain of the 70 kDa subunit (RPA70N). Here we describe the optimization of a diphenylpyrazole carboxylic acid series of inhibitors of these RPA-protein interactions. We evaluated substituents on the aromatic rings as well as the type and geometry of the linkers used to combine fragments, ultimately leading to submicromolar inhibitors of RPA70N protein-protein interactions.

  DOI：

  10.1021/ml5003629

文献信息

• Synthesis and in vitro Evaluation of West Nile Virus Protease Inhibitors Based on the 1,3,4,5‐Tetrasubstituted 1 <i>H</i> ‐Pyrrol‐2(5 <i>H</i> )‐one Scaffold
  作者：Yaojun Gao、Sanjay Samanta、Taian Cui、Yulin Lam

  DOI：10.1002/cmdc.201300244

  日期：2013.9

  1H‐pyrrol‐2(5H)‐one scaffold was identified by screening a small library of nonpeptidic compounds. Optimization of this initial hit by the synthesis and screening of a focused library of compounds with this scaffold led to the identification of a novel uncompetitive inhibitor ((−)‐1a16, IC50=2.2±0.7 μM) of the WNV NS2B–NS3 protease. Molecular docking of the chiral compound onto the WNV protease indicates

  西尼罗河病毒（WNV）是黄病毒科的成员，是一种由蚊子传播的病原体，每年引起大量人类感染。目前尚无可用于人类的针对WNV的疫苗或抗病毒疗法。因此，迫切需要开发针对该病毒的新化学疗法。在这项研究中，通过筛选一个小的非肽类化合物文库，鉴定了具有1,3,4,5-四取代的1 H-吡咯-2（5 H）-one支架的WNV NS2B–NS3蛋白酶抑制剂。该初始命中通过合成的优化和化合物与本支架导致的新颖非竞争性抑制剂的鉴定（（聚焦文库的筛选- ） - 1a16，IC 50 = 2.2±0.7μ中号）的WNV NS2B–NS3蛋白酶。手性化合物与WNV蛋白酶的分子对接表明1a16的R 对映体干扰了NS2B辅因子和NS3蛋白酶结构域之间的生产性相互作用，因此是抑制WNV NS2B–NS3蛋白酶的优选异构体。
• Sulfamic Acid as an Effective Catalyst in Solvent‐Free Synthesis of β‐Enaminoketone Derivatives and X‐ray Crystallography of Their Representatives
  作者：Min Xia、Bin Wu、Guo‐Feng Xiang

  DOI：10.1080/00397910701873250

  日期：2008.3.28

  Abstract Two types of β‐enaminoketone derivatives of 3‐(2‐oxo‐2‐arylethylidene)‐3,4‐dihydro‐1H‐quinoxalin‐2‐ones and 3‐(2‐oxo‐2‐arylethylidene)‐3,4‐dihydro‐benzo[1,4]oxazin‐2‐ ones were effectively and conveniently prepared in good to excellent yields under solvent‐free conditions via the catalysis of sulfamic acid in the corresponding condensations of o‐phenylenediamine and o‐aminophenol with ethyl

  摘要 3-(2-oxo-2-arylethylidene)-3,4-dihydro-1H-quinoxalin-2-ones和3-(2-oxo-2-arylethylidene)-3,4的两种β-烯氨基酮衍生物在无溶剂条件下，通过氨基磺酸催化邻苯二胺和邻氨基苯酚与乙基 2 的相应缩合反应，可以有效且方便地制备-二氢苯并[1,4]恶嗪-2-类化合物。 ,4-dioxo-4-arylbutyrate 分别。化合物经 IR、1H NMR 和 13C NMR 确证，代表性化合物通过 X 射线晶体学进一步确定。
• Diphenylpyrazoles as Replication Protein A Inhibitors
  作者：Alex G. Waterson、J. Phillip Kennedy、James D. Patrone、Nicholas F. Pelz、Michael D. Feldkamp、Andreas O. Frank、Bhavatarini Vangamudi、Elaine M. Souza-Fagundes、Olivia W. Rossanese、Walter J. Chazin、Stephen W. Fesik

  DOI：10.1021/ml5003629

  日期：2015.2.12

  Replication Protein A is the primary eukaryotic ssDNA binding protein that has a central role in initiating the cellular response to DNA damage. RPA recruits multiple proteins to sites of DNA damage via the N-terminal domain of the 70 kDa subunit (RPA70N). Here we describe the optimization of a diphenylpyrazole carboxylic acid series of inhibitors of these RPA-protein interactions. We evaluated substituents on the aromatic rings as well as the type and geometry of the linkers used to combine fragments, ultimately leading to submicromolar inhibitors of RPA70N protein-protein interactions.