(E)-4-(3,4-dimethylphenyl)-4-oxo-2-butenoic acid phenylamide | 135979-09-8

• 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-(3,4-dimethylphenyl)-4-oxo-2-butenoic acid phenylamide
• 英文别名: (E)-4-(3,4-dimethylphenyl)-4-oxo-N-phenylbut-2-enamide
• CAS: 135979-09-8
• 化学式: C₁₈H₁₇NO₂
• 分子量: 279.338
• InChiKey: XSNSHHOUSPIDIT-ZHACJKMWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 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：

  哌啶 、 (E)-4-(3,4-dimethylphenyl)-4-oxo-2-butenoic acid phenylamide 在 sodium carbonate 作用下， 以 甲醇 为溶剂， 生成 4-(3,4-dimethylphenyl)-4-oxo-N-phenyl-2-(piperidin-1-yl)butanamide
  参考文献：
  名称：

  Reactivity of (E)-4-aryl-4-oxo-2-butenoic acid phenylamides with piperidine and benzylamine: kinetic and theoretical study

  摘要：

  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.

  DOI：

  10.1007/s00706-014-1223-8
• 作为产物：
  描述：

  (E)-4-(3,4-dimethylphenyl)-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-(3,4-dimethylphenyl)-4-oxo-2-butenoic acid phenylamide
  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

• 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 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.
• The in vitro protective effects of the three novel nanomolar reversible inhibitors of human cholinesterases against irreversible inhibition by organophosphorous chemical warfare agents
  作者：Maja D. Vitorović-Todorović、Franz Worek、Andrej Perdih、Sonja Đ. Bauk、Tamara B. Vujatović、Ilija N. Cvijetić

  DOI：10.1016/j.cbi.2019.06.027

  日期：2019.8

  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.
• (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.
• 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.