(E)-4-[2-(3,4,5-trimethoxyphenyl)vinyl]benzoic acid | 360789-59-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: (E)-4-[2-(3,4,5-trimethoxyphenyl)vinyl]benzoic acid
• 英文别名: 4-[(E)-2-(3,4,5-trimethoxyphenyl)vinyl]benzoic acid；4-[(E)-2-(3,4,5-trimethoxyphenyl)ethenyl]benzoic acid
• CAS: 360789-59-9
• 化学式: C₁₈H₁₈O₅
• 分子量: 314.338
• InChiKey: ZIEUMSNBDHAVCX-SNAWJCMRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (E)-4-[2-(3,4,5-trimethoxyphenyl)vinyl]benzoic acid 在 甲基磺酰氯 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 醋酸异丙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 51.0h， 生成 (E)-N-(2-(1H-imidazol-1-yl)-2-phenylethyl)-4-(3,4,5-trimethoxystyryl)benzamide
  参考文献：
  名称：

  Small-Molecule Inhibitors of 25-Hydroxyvitamin D-24-Hydroxylase (CYP24A1): Synthesis and Biological Evaluation

  摘要：

  The synthesis of imidazole styrylbenzamide, tert-butyl styryl-imidazole, and tert-butyl styrylsulfonate derivatives is described. Evaluation of binding affinity and inhibitory activity against CYP24A1 identified the imidazole styrylbenzamides as potent inhibitors of CYP24A1, having selectivity with respect to CYP27B1 comparable with or greater than that of the standard ketoconazole. Further evaluation of the 3,5-dimethoxy and 3,4,5-trimethoxy derivatives in chronic lymphocytic leukemia cells revealed that co-treatment of 1 alpha,25-dihydroxyvitamin D-3 plus inhibitor coordinately upregulated GADD45 alpha and CDKN1A. Docking experiments on the inhibitors in the CYP24A1 enzyme active site suggest the compounds reach the active site through the vitamin D access tunnel and are exposed to multiple hydrophobic residues. The imidazole styrylbenzamides are optimally positioned to allow interaction of the imidazole with the heme, and, in the case of the methoxy derivatives, a hydrogen bond between the 3-methoxy group and Gln82 stabilizes the molecule in a favorable active conformation.

  DOI：

  10.1021/jm5009314
• 作为产物：
  描述：

  (4-甲氧羰基苄基)三苯基溴化膦 在 氢氧化钾 、 18-冠醚-6 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 13.08h， 生成 (E)-4-[2-(3,4,5-trimethoxyphenyl)vinyl]benzoic acid
  参考文献：
  名称：

  5‘-Tethered Stilbene Derivatives as Fidelity- and Affinity-Enhancing Modulators of DNA Duplex Stability

  摘要：

  A series of 5'-linked stilbene-DNA conjugates with different substituents in the distal aromatic ring of the stilbene was prepared, and the effect of the modifications on duplex stability was determined via UV-melting curves. A trimethoxystilbene derivative as a 5'-substituent increases duplex melting points by up to 12.2 degrees C per modification. With this alkoxystilbene substituent, terminal mismatches in DNA duplexes lower the melting point by up to 23.4 degrees C over the perfectly matched control, whereas terminal mismatches in unmodified DNA cause melting point depressions of no more than 6.1 degrees C. An aminomethylstilbene substituent linked to an oligopyrrolamide minor groove binder increases the melting point of an all-A/T decamer by up to 32.7 degrees C, thus shifting the melting point into a range typical for duplexes with statistical G/C-content. An affinity- and selectivity-enhancing effect was also observed when the trimethoxystilbene cap was employed on a small DNA microarray. The phosphoramidite of the trimethoxystilbene can be readily employed in automatic DNA synthesis, facilitating the generation of DNA chips with improved fidelity.

  DOI：

  10.1021/ja0394434

文献信息

• Luminescent supramolecular assemblies based on hydrogen­bonded complexes of stilbenecarboxylic acids and dithieno[3,2­b:2′,3′­d]thiophene­2­carboxylic acids with a tris(imidazoline) base
  作者：Frank Osterod、Lars Peters、Arno Kraft、Takeshi Sano、John J. Morrison、Neil Feeder、Andrew B. Holmes

  DOI：10.1039/b009406o

  日期：——

  The synthesis of a number of stilbenecarboxylic acids, tetrazolylstilbenes and dithieno[3,2-b:2′,3′-d]thiophene-2-carboxylic acids is reported. These organic acids form non-covalent complexes with an imidazoline base, 1,3,5-tris(4,5-dihydroimidazol-2-yl)benzene 13. Two X-ray crystal structures confirm hydrogen bonds between carboxylate ligands and meta-positioned protonated imidazoline groups. The complexes possess a surprisingly flat disk-like shape with various close contacts between adjacent molecules. Most stilbene and dithieno[3,2-b:2′,3′-d]thiophene derivatives show strong blue or blue–green photoluminescence in solution, whereas fluorescence in the solid state is almost completely quenched.

  报道了一系列芪类羧酸、四唑基芪类化合物以及二噻吩[3,2-b:2′,3′-d]噻吩-2-羧酸的合成。这些有机酸与咪唑啉碱基，即1,3,5-三(4,5-二氢咪唑-2-基)苯13形成了非共价复合物。两个X射线晶体结构证实了羧酸盐配体与间位质子化的咪唑啉基团之间存在氢键。这些复合物具有出乎意料的扁平盘状形态，相邻分子之间存在多种紧密接触。大多数芪类和二噻吩[3,2-b:2′,3′-d]噻吩衍生物在溶液中表现出强烈的蓝色或蓝绿色光致发光，而在固态下荧光几乎完全淬灭。
• 5‘-Tethered Stilbene Derivatives as Fidelity- and Affinity-Enhancing Modulators of DNA Duplex Stability
  作者：Zeynep Dogan、Ralph Paulini、Jan A. Rojas Stütz、Sukunath Narayanan、Clemens Richert

  DOI：10.1021/ja0394434

  日期：2004.4.1

  A series of 5'-linked stilbene-DNA conjugates with different substituents in the distal aromatic ring of the stilbene was prepared, and the effect of the modifications on duplex stability was determined via UV-melting curves. A trimethoxystilbene derivative as a 5'-substituent increases duplex melting points by up to 12.2 degrees C per modification. With this alkoxystilbene substituent, terminal mismatches in DNA duplexes lower the melting point by up to 23.4 degrees C over the perfectly matched control, whereas terminal mismatches in unmodified DNA cause melting point depressions of no more than 6.1 degrees C. An aminomethylstilbene substituent linked to an oligopyrrolamide minor groove binder increases the melting point of an all-A/T decamer by up to 32.7 degrees C, thus shifting the melting point into a range typical for duplexes with statistical G/C-content. An affinity- and selectivity-enhancing effect was also observed when the trimethoxystilbene cap was employed on a small DNA microarray. The phosphoramidite of the trimethoxystilbene can be readily employed in automatic DNA synthesis, facilitating the generation of DNA chips with improved fidelity.
• Small-Molecule Inhibitors of 25-Hydroxyvitamin D-24-Hydroxylase (CYP24A1): Synthesis and Biological Evaluation
  作者：Salvatore Ferla、Ahmed S. Aboraia、Andrea Brancale、Christopher J. Pepper、Jinge Zhu、Justin T. Ochalek、Hector F. DeLuca、Claire Simons

  DOI：10.1021/jm5009314

  日期：2014.9.25

  The synthesis of imidazole styrylbenzamide, tert-butyl styryl-imidazole, and tert-butyl styrylsulfonate derivatives is described. Evaluation of binding affinity and inhibitory activity against CYP24A1 identified the imidazole styrylbenzamides as potent inhibitors of CYP24A1, having selectivity with respect to CYP27B1 comparable with or greater than that of the standard ketoconazole. Further evaluation of the 3,5-dimethoxy and 3,4,5-trimethoxy derivatives in chronic lymphocytic leukemia cells revealed that co-treatment of 1 alpha,25-dihydroxyvitamin D-3 plus inhibitor coordinately upregulated GADD45 alpha and CDKN1A. Docking experiments on the inhibitors in the CYP24A1 enzyme active site suggest the compounds reach the active site through the vitamin D access tunnel and are exposed to multiple hydrophobic residues. The imidazole styrylbenzamides are optimally positioned to allow interaction of the imidazole with the heme, and, in the case of the methoxy derivatives, a hydrogen bond between the 3-methoxy group and Gln82 stabilizes the molecule in a favorable active conformation.