(E)-4-(2,4,6-triethylphenyl)-4-oxo-2-butenoic acid

• 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-(2,4,6-triethylphenyl)-4-oxo-2-butenoic acid
• 英文别名: 4-oxo-4-(2,4,6-triethyl-phenyl)-trans-crotonic acid；4-Oxo-4-(2,4,6-triaethyl-phenyl)-trans-crotonsaeure；(E)-4-oxo-4-(2,4,6-triethylphenyl)but-2-enoic acid
• 化学式: C₁₆H₂₀O₃
• mdl: MFCD25721635
• 分子量: 260.333
• InChiKey: RYHVOTZSLAPJID-BQYQJAHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.375
• 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-(2,4,6-triethylphenyl)-4-oxo-2-butenoic acid 、 巯基乙酸 以 甲醇 为溶剂， 以70%的产率得到2-Carboxymethylsulfanyl-4-oxo-4-(2,4,6-triethyl-phenyl)-butyric 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
• 作为产物：
  描述：

  马来酸酐 、 1,3,5-三乙基苯 在 aluminum (III) chloride 、 盐酸 作用下， 以 二氯甲烷 、 水 为溶剂， 以65%的产率得到(E)-4-(2,4,6-triethylphenyl)-4-oxo-2-butenoic acid
  参考文献：
  名称：

  Antiproliferative activity of aroylacrylic acids. Structure-activity study based on molecular interaction fields

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2011.04.043

文献信息

• Cramer et al., Journal of the American Pharmaceutical Association (1912), 1948, vol. 37, p. 439,445
  作者：Cramer et al.

  DOI：——

  日期：——
• 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.
• 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.