(E)-4-(4-Methoxyphenyl)-4-oxo-N-phenylbut-2-enamide | 1220094-89-2

• 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-(4-Methoxyphenyl)-4-oxo-N-phenylbut-2-enamide
• 英文别名: (E)-4-(4-methoxyphenyl)-4-oxo-N-phenylbut-2-enamide
• CAS: 1220094-89-2
• 化学式: C₁₇H₁₅NO₃
• 分子量: 281.311
• InChiKey: FYVGMIBLVVBKHX-VAWYXSNFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,8-辛二胺 、 (E)-4-(4-Methoxyphenyl)-4-oxo-N-phenylbut-2-enamide 以 氯仿 、 苯 为溶剂， 以97.43%的产率得到4-(4-methoxyphenyl)-2-{8-[3-(4-methoxyphenyl)-3-oxo-1-phenylcarbamoyl-propylamino]-octylamino}-4-oxo-N-phenyl-butyramide
  参考文献：
  名称：

  4-芳基-4-氧代-N-苯基-2-氨基丁酰胺作为乙酰基和丁酰胆碱酯酶抑制剂。基于分子相互作用场的制备，抗胆碱酯酶活性，对接研究和3D结构-活性关系

  摘要：

  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。

  DOI：

  10.1016/j.bmc.2009.12.042
• 作为产物：
  描述：

  (E)-4-(4-methoxyphenyl)-4-oxo-2-butenoic acid 在 三氯氧磷 作用下， 以 四氢呋喃 为溶剂， 生成 (E)-4-(4-Methoxyphenyl)-4-oxo-N-phenylbut-2-enamide
  参考文献：
  名称：

  (E)-4-Aryl-4-oxo-2-butenoic acid amides, chalcone–aroylacrylic acid chimeras: Design, antiproliferative activity and inhibition of tubulin polymerization

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2013.01.006

文献信息

• 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.
• Reactivity of (E)-4-aryl-4-oxo-2-butenoic acid arylamides toward 2-mercaptoethanol. A LFER study
  作者：Ilija N. Cvijetić、Maja D. Vitorović-Todorović、Ivan O. Juranić、Branko J. Drakulić

  DOI：10.1007/s00706-013-1084-6

  日期：2013.12

  The reactivity of fifteen (E)-4-aryl-4-oxo-2-butenoic (aroylacrylic) acid arylamides toward thiols was studied, measuring the rate constants of the addition of model thiol nucleophile, 2-mercaptoethanol. The influence of the variation of the substituents on the phenyl rings on the rate of reaction was quantified using the Hammett substituent constants and descriptors derived from ab initio or semiempirical calculations (atomic charges, HOMO, and LUMO). Statistically significant linear correlations between second-order rate constants and Hammett substituent constants, as well as energies of LUMO orbitals, were obtained. Substituents on both aroyl and arylamido moieties were shown to influence the reactivity of studied compounds toward thiols. The regioselectivity of reaction was confirmed by NMR spectroscopy. Exclusively beta-addition product with respect to the aroyl keto group was obtained. The determined enthalpy and entropy of activation were found to be in agreement with the proposed reaction mechanism, which includes a highly ordered transition state.
• (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.
• 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。