(E)-4-(5,6,7,8-tetrahydro-2-naphthalenyl)-4-oxo-2-butenoic acid phenylamide | 1220094-92-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (E)-4-(5,6,7,8-tetrahydro-2-naphthalenyl)-4-oxo-2-butenoic acid phenylamide
• 英文别名: (E)-4-(5,6,7,8-tetrahydronaphtalenyl)-4-oxo-2-butenoic acid phenylamide；(E)-4-oxo-N-phenyl-4-(5,6,7,8-tetrahydronaphthalen-2-yl)but-2-enamide
• CAS: 1220094-92-7
• 化学式: C₂₀H₁₉NO₂
• 分子量: 305.376
• InChiKey: NTANDKLHRKOOMB-OUKQBFOZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 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-(5,6,7,8-tetrahydro-2-naphthalenyl)-4-oxo-2-butenoic acid phenylamide 、 2-巯基乙醇 在 三乙胺 作用下， 以 甲醇 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  Reactivity of (E)-4-aryl-4-oxo-2-butenoic acid arylamides toward 2-mercaptoethanol. A LFER study

  摘要：

  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.

  DOI：

  10.1007/s00706-013-1084-6
• 作为产物：
  描述：

  (E)-4-(5,6,7,8-tetrahydronaphthalen-2-yl)-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-(5,6,7,8-tetrahydro-2-naphthalenyl)-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

• 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。
• ELKADY M.; ELHASHASH M. A.; SAYED G. H.; MOHAMED M. M., REV. ROUM. CHIM., 1980, 25, NO 9-10, 1361-1366
  作者：ELKADY M.、 ELHASHASH M. A.、 SAYED G. H.、 MOHAMED M. M.

  DOI：——

  日期：——
• (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 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.