(E)-4-phenyl-4-oxo-2-butenoic acid phenylamide | 36977-69-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (E)-4-phenyl-4-oxo-2-butenoic acid phenylamide
• 英文别名: β-benzoylacrylic acid N-phenylamide；trans-2-benzoylacrylanilide；trans-3-Benzoylacrylanilid；(E)-4-oxo-N,4-diphenylbut-2-enamide
• CAS: 36977-69-2
• 化学式: C₁₆H₁₃NO₂
• 分子量: 251.285
• InChiKey: WZSDQUTUJMGEAI-VAWYXSNFSA-N

物化性质

• 熔点：
  159-160 °C
• 沸点：
  450.8±41.0 °C(Predicted)
• 密度：
  1.204±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (E)-4-phenyl-4-oxo-2-butenoic acid phenylamide 、 N-(1,2,3,4-tetrahydroacridin-9-yl)octane-1,8-diamine 以 氯仿 、 甲苯 为溶剂， 反应 24.0h， 以100%的产率得到4-N-diphenyl-4-oxo-2-[8-(1,2,3,4-tetrahydroacridin-9-ylamino)octylamino]butanamide
  参考文献：
  名称：

  The in vitro protective effects of the three novel nanomolar reversible inhibitors of human cholinesterases against irreversible inhibition by organophosphorous chemical warfare agents

  摘要：

  Acetylcholinesterase (AChE) is an enzyme which terminates the cholinergic neurotransmission, by hydrolyzing acetylcholine at the nerve and nerve-muscle junctions. The reversible inhibition of AChE was suggested as the pre-treatment option of the intoxications caused by nerve agents. Based on our derived 3D-QSAR model for the reversible AChE inhibitors, we designed and synthesized three novel compounds 8-10, joining the tacrine and aroylacrylic acid phenylamide moieties, with a longer methylene chain to target two distinct, toplogically separated anionic areas on the AChE. The targeted compounds exerted low nanomolar to subnanomolar potency toward the E. eel and human AChE's as well as the human BChE and showed mixed inhibition type in kinetic studies. All compounds were able to slow down the irreversible inhibition of the human AChE by several nerve agents including tabun, soman and VX, with the estimated protective indices around 5, indicating a valuable level of protection. Putative noncovalent interactions of the selected ligand 10 with AChE active site gorge were finally explored by molecular dynamics simulation suggesting a formation of the salt bridge between the protonated linker amino group and the negatively charged Asp74 carboxylate side chain as a significant player for the successful molecular recognition in line with the design strategy. The designed compounds may represent a new class of promising leads for the development of more effective pre-treatment options.

  DOI：

  10.1016/j.cbi.2019.06.027
• 作为产物：
  描述：

  3-溴-4-氧代-4-苯基丁酸 在 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 苯 为溶剂， 反应 1.0h， 生成 (E)-4-phenyl-4-oxo-2-butenoic acid phenylamide
  参考文献：
  名称：

  4-苯甲酰基-2-氮杂环丁烷酮的替代途径

  摘要：

  通过末端N 1 -C 4键形成的环卤代氢卤代以明确的成核过程从3-苯甲酰基-3-溴丙酰苯胺中得到N-芳基-4-苯甲酰基-2-氮杂环丁酮。

  DOI：

  10.1016/s0040-4039(00)78822-8

文献信息

• 4-Aryl-4-oxo-N-phenyl-2-aminylbutyramides as acetyl- and butyrylcholinesterase inhibitors. Preparation, anticholinesterase activity, docking study, and 3D structure–activity relationship based on molecular interaction fields
  作者：Maja D. Vitorović-Todorović、Ivan O. Juranić、Ljuba M. Mandić、Branko J. Drakulić

  DOI：10.1016/j.bmc.2009.12.042

  日期：2010.2

  literature, confirmed that alkyl substitution on aroyl moiety of molecules is requisite for inhibition activity. The presence of hydrophobic moiety at close distance from hydrogen bond acceptor has favorable influence on inhibition potency. Docking studies show that compounds probably bind in the middle of the AChE active site gorge, but are buried deeper inside BChE active site gorge, as a consequence

  4-芳基-4-氧代-N的合成及抗胆碱酯酶活性据报道，新型的可逆的，中等效力的胆碱酯酶抑制剂-苯基-2-氨基丁基丁酰胺。芳酰基部分上的简单取代基变化将抗AChE活性改变了两个数量级。丁酸部分2位的杂（ali）环的取代和类型也决定了AChE / BChE的选择性。最有效的化合物表现出混合型抑制作用，表明它们与游离酶和酶-底物复合物结合。对报道的化合物以及具有从文献中获得的具有类似效力的化合物的与排列无关的3D QSAR研究证实，分子的芳酰基部分上的烷基取代是抑制活性所必需的。距离氢键受体很近的疏水部分的存在对抑制效能具有有利的影响。
• High‐Throughput Experimentation and Machine Learning‐Assisted Optimization of Iridium‐Catalyzed Cross‐Dimerization of Sulfoxonium Ylides
  作者：Yougen Xu、Yadong Gao、Lebin Su、Haiting Wu、Hao Tian、Majian Zeng、Chunqiu Xu、Xinwei Zhu、Kuangbiao Liao

  DOI：10.1002/anie.202313638

  日期：2023.11.27

  A novel and convenient approach that combines high‐throughput experimentation (HTE) with machine learning (ML) technologies to achieve the first selective cross‐dimerization of sulfoxonium ylides via iridium catalysis is presented. A variety of valuable amide‐, ketone‐, ester‐, and N‐heterocycle‐substituted unsymmetrical E‐alkenes are synthesized in good yields with high stereoselectivities. This mild method avoids the use of diazo compounds and is characterized by simple operation, high step‐economy, and excellent chemoselectivity and functional group compatibility. The combined experimental and computational studies identify an amide‐sulfoxonium ylide as a carbene precursor. Furthermore, a comprehensive exploration of the reaction space is also performed (600 reactions) and a machine learning model for reaction yield prediction has been constructed.

  摘要 介绍了一种结合高通量实验（HTE）和机器学习（ML）技术的新颖而便捷的方法，该方法首次通过铱催化实现了磺鎓酰化物的选择性交叉二聚。该研究以良好的产率和较高的立体选择性合成了多种有价值的酰胺、酮、酯和 N-杂环取代的不对称 E-烯。这种温和的方法避免了重氮化合物的使用，具有操作简单、步骤经济性高、化学选择性和官能团兼容性好的特点。结合实验和计算研究，确定了一种酰胺基磺酰亚胺作为碳烯前体。此外，还对反应空间（600 个反应）进行了全面探索，并构建了一个用于预测反应产率的机器学习模型。
• (E)-4-Aryl-4-oxo-2-butenoic acid amides, chalcone–aroylacrylic acid chimeras: Design, antiproliferative activity and inhibition of tubulin polymerization
  作者：Maja D. Vitorović-Todorović、Aleksandra Erić-Nikolić、Branka Kolundžija、Ernest Hamel、Slavica Ristić、Ivan O. Juranić、Branko J. Drakulić

  DOI：10.1016/j.ejmech.2013.01.006

  日期：2013.4

  Antiproliferative activity of twenty-nine (E)-4-aryl-4-oxo-2-butenoic acid amides against three human tumor cell lines (HeLa, FemX, and K562) is reported. Compounds showed antiproliferative activity in one-digit micromolar to submicromolar concentrations. The most active derivatives toward all the cell lines tested bear alkyl substituents on the aroyl moiety of the molecules. Fourteen compounds showed tubulin assembly inhibition at concentrations <20 mu M. The most potent inhibitor of tubulin assembly was unsubstituted compound 1, with IC50 = 2.9 mu M. Compound 23 had an oral LD50 in vivo of 45 mg/kg in mice. Cell cycle analysis on K562 cells showed that compounds 1, 2 and 23 caused accumulation of cells in the G2/M phase, but inhibition of microtubule polymerization is not the principal mode of action of the compounds. Nevertheless, they may be useful leads for the design of a new class of antitubulin agents. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Ismail, Mohamed Fekry; Enayat, Ebtesam Ismail; Bassiouny, Fakhry Abdel Aziz El, Acta Chimica Hungarica, 1991, vol. 128, # 3, p. 365 - 373
  作者：Ismail, Mohamed Fekry、Enayat, Ebtesam Ismail、Bassiouny, Fakhry Abdel Aziz El、Younis, Hamed Ahmed

  DOI：——

  日期：——
• Reactivity of (E)-4-aryl-4-oxo-2-butenoic acid phenylamides with piperidine and benzylamine: kinetic and theoretical study
  作者：Ilija N. Cvijetić、Maja D. Vitorović-Todorović、Ivan O. Juranić、Đura J. Nakarada、Milica D. Milosavljević、Branko J. Drakulić

  DOI：10.1007/s00706-014-1223-8

  日期：2014.8

  Rates of the aza-Michael addition of piperidine and benzylamine to thirteen (E)-4-aryl-4-oxo-2-butenoic acid phenylamides (AACPs) are reported. Progress of the reaction was monitored by UV/Vis spectroscopy. The 2D NMR spectra confirmed regioselectivity of the reactions. Piperidine and benzylamine provide exclusively beta-adducts in respect to the aroyl keto group. Influence of the substituents of the aroyl phenyl ring of AACPs on the rate of the reaction was quantified by Hammett substituent constants, partial atomic charges, and the energies of frontier orbitals. Good correlations between second-order rate constants and the Hammett substituent constants were obtained (r = 0.98, piperidine; r = 0.94, benzylamine) for para-, and meta-, para-substituted derivatives. Best correlations were obtained with the energies of the lowest unoccupied molecular orbitals of compounds, derived from the MP2 level of theory. Calculated UV/Vis spectra of representative AACPs and their Michael adduct with piperidine and benzylamine are in fair agreement with experimentally obtained data.