(E)-4-(2,4-diisopropylphenyl)-4-oxo-2-butenoic acid

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (E)-4-(2,4-diisopropylphenyl)-4-oxo-2-butenoic acid
• 英文别名: (E)-4-[2,4-di(propan-2-yl)phenyl]-4-oxobut-2-enoic acid
• 化学式: C₁₆H₂₀O₃
• 分子量: 260.333
• InChiKey: QVDBHBHQEPGTRI-BQYQJAHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-4-(2,4-diisopropylphenyl)-4-oxo-2-butenoic acid 在 三氯氧磷 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 生成 N-cyclohexyl-4-(2,4-diisopropylphenyl)-4-oxo-2-(1-imidazolyl)butanamide
  参考文献：
  名称：

  Structural modifications of 4-aryl-4-oxo-2-aminylbutanamides and their acetyl- and butyrylcholinesterase inhibitory activity. Investigation of AChE–ligand interactions by docking calculations and molecular dynamics simulations

  摘要：

  Congeneric set of thirty-eight 4-aryl-4-oxo-2-(N-aryl/cycloalkyl)butanamides has been designed, synthesized and evaluated for acetyl- and butyrylcholinesterase inhibitory activity. Structural variations included cycloalkylamino group attached to C2 position of butanoyl moiety, and variation of amido moiety of molecules. Twelve compounds, mostly piperidino and imidazolo derivatives, inhibited AChE in low micromolar range, and were inactive toward BChE. Several N-methylpiperazino derivatives showed inhibition of BChE in low micromolar or submicromolar concentrations, and were inactive toward AChE. Therefore, the nature of the cycloalkylamino moiety governs the AChE/BChE selectivity profile of compounds. The most active AChE inhibitor showed mixed-type inhibition modality, indicating its binding to free enzyme and to enzyme-substrate complex. Thorough docking calculations of the seven most potent AChE inhibitors from the set, showed that the hydrogen bond can be formed between amide -NH- moiety of compounds and -OH group of Tyr 124. The 10 ns unconstrained molecular dynamic simulation of the AChE- compound 18 complex shows that this interaction is the most persistent. This is, probably, the major anchoring point for the binding. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.05.008
• 作为产物：
  描述：

  马来酸酐 、 1,3-二异丙基苯 在 三氯化铝 作用下， 以 二氯甲烷 为溶剂， 生成 (E)-4-(2,4-diisopropylphenyl)-4-oxo-2-butenoic acid
  参考文献：
  名称：

  2-[(Carboxymethyl)sulfanyl]-4-oxo-4-arylbutanoic Acids Selectively Suppressed Proliferation of Neoplastic Human HeLa Cells. A SAR/QSAR Study

  摘要：

  A series of twenty alkyl-, halo-, and methoxy-aryl-substituted 2-[(carboxymethyl)sulfanyl]-4-oxo-4-arylbutanoic acids were synthesized. The new compounds, called CSAB, suppressed proliferation of human cervix carcinoma, HeLa cells, in vitro in a concentration range of 0.644 to 29.48 mu M/L. Two compounds exhibit antiproliferative activity in sub-micromolar concentrations (16, 19). Five compounds act in low micromolar concentrations (< 2 mu M/L). The most active compounds exert lower cytotoxicity toward healthy human peripheral blood mononuclear cells (PBMC and PBMC+PHA) (selectivity indexes > 10). A strong structure-activity relationship, using estimated log P values and BCUT descriptors, was observed.

  DOI：

  10.1021/jm0502889

文献信息

• Synthesis, structure and magnetic properties of the first copper(II) complex with an (E)-4-aryl-4-oxo-2-butenoato ligand
  作者：Zoran M. Miodragović、Goran A. Bogdanović、Bojana B. Krajčinović、Branko J. Drakulić、Vladan B. Kusigerski、Djenana U. Miodragović、Vojislav V. Spasojević、Ismet M. Hodžić、Ivan O. Juranić

  DOI：10.1016/j.inoche.2006.07.029

  日期：2006.12

  were determined by single crystal X-ray analyses and are preliminarily discussed. This is the first complex of a transition metal with ligand L, as well as the first determined crystal structure of a metal complex with this type of ligand. Analysis of the magnetic susceptibility measurements of the isolated [Cu2L4(C2H5OH)2] · H2O complex shows the existence of a strong anti-ferromagnetic intradimer coupling

  摘要 成功合成了一种具有 (E)-4-(2,4-二异丙基苯基)-4-oxo-2-butenoato 配体 (L) 的新型双核 Cu(II) 配合物，并通过元素分析和红外光谱对其进行了表征。(E)-4-(2,4-二异丙基苯基)-4-氧代-2-丁烯酸(HL)的结构，以及相应的(四)-μ-[(E)-4-(2,4-二异丙基苯基)-4-氧代-2-丁烯基]-双(乙醇)-铜(II) 络合物[Cu2L4(C2H5OH)2]，通过单晶X 射线分析确定并初步讨论。这是第一个过渡金属与配体 L 的配合物，也是第一个确定的金属配合物与此类配体的晶体结构。对分离的 [Cu2L4(C2H5OH)2]·H2O 复合物的磁化率测量的分析表明存在强反铁磁二聚体耦合，
• 2-[(Carboxymethyl)sulfanyl]-4-oxo-4-arylbutanoic Acids Selectively Suppressed Proliferation of Neoplastic Human HeLa Cells. A SAR/QSAR Study
  作者：Branko J. Drakulić、Zorica D. Juranić、Tatjana P. Stanojković、Ivan O. Juranić

  DOI：10.1021/jm0502889

  日期：2005.8.1

  A series of twenty alkyl-, halo-, and methoxy-aryl-substituted 2-[(carboxymethyl)sulfanyl]-4-oxo-4-arylbutanoic acids were synthesized. The new compounds, called CSAB, suppressed proliferation of human cervix carcinoma, HeLa cells, in vitro in a concentration range of 0.644 to 29.48 mu M/L. Two compounds exhibit antiproliferative activity in sub-micromolar concentrations (16, 19). Five compounds act in low micromolar concentrations (< 2 mu M/L). The most active compounds exert lower cytotoxicity toward healthy human peripheral blood mononuclear cells (PBMC and PBMC+PHA) (selectivity indexes > 10). A strong structure-activity relationship, using estimated log P values and BCUT descriptors, was observed.
• (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.
• Antiproliferative activity of aroylacrylic acids. Structure-activity study based on molecular interaction fields
  作者：Branko J. Drakulić、Tatjana P. Stanojković、Željko S. Žižak、Milan M. Dabović

  DOI：10.1016/j.ejmech.2011.04.043

  日期：2011.8

  Antiproliferative activity of 27 phenyl-substituted 4-aryl-4-oxo-2-butenoic acids (aroylacrylic acids) toward Human cervix carcinoma (HeLa). Human chronic myelogenous leukemia (K562) and Human colon tumor (LS174) cell lines in vitro are reported. Compounds are active toward all examined cell lines. The most active compounds bear two or three branched alkyl or cycloalkyl substituents on phenyl moiety having potencies in low micromolar ranges. One of most potent derivatives arrests the cell cycle at S phase in HeLa cells. The 3D QSAR study, using molecular interaction fields (MIF) and derived alignment independent descriptors (GRIND-2), rationalize the structural characteristics correlated with potency of compounds. Covalent chemistry, most possibly involved in the mode of action of reported compounds, was quantitatively accounted using frontier molecular orbitals. Pharmacophoric pattern of most potent compounds are used as a template for virtual screening, to find similar ones in database of compounds screened against DTP-NCI 60 tumor cell lines. Potency of obtained hits is well predicted. (C) 2011 Elsevier Masson SAS. All rights reserved.
• Structural modifications of 4-aryl-4-oxo-2-aminylbutanamides and their acetyl- and butyrylcholinesterase inhibitory activity. Investigation of AChE–ligand interactions by docking calculations and molecular dynamics simulations
  作者：Maja D. Vitorović-Todorović、Catherine Koukoulitsa、Ivan O. Juranić、Ljuba M. Mandić、Branko J. Drakulić

  DOI：10.1016/j.ejmech.2014.05.008

  日期：2014.6

  Congeneric set of thirty-eight 4-aryl-4-oxo-2-(N-aryl/cycloalkyl)butanamides has been designed, synthesized and evaluated for acetyl- and butyrylcholinesterase inhibitory activity. Structural variations included cycloalkylamino group attached to C2 position of butanoyl moiety, and variation of amido moiety of molecules. Twelve compounds, mostly piperidino and imidazolo derivatives, inhibited AChE in low micromolar range, and were inactive toward BChE. Several N-methylpiperazino derivatives showed inhibition of BChE in low micromolar or submicromolar concentrations, and were inactive toward AChE. Therefore, the nature of the cycloalkylamino moiety governs the AChE/BChE selectivity profile of compounds. The most active AChE inhibitor showed mixed-type inhibition modality, indicating its binding to free enzyme and to enzyme-substrate complex. Thorough docking calculations of the seven most potent AChE inhibitors from the set, showed that the hydrogen bond can be formed between amide -NH- moiety of compounds and -OH group of Tyr 124. The 10 ns unconstrained molecular dynamic simulation of the AChE- compound 18 complex shows that this interaction is the most persistent. This is, probably, the major anchoring point for the binding. (C) 2014 Elsevier Masson SAS. All rights reserved.