(E)-3-(4-nitrophenyl)-1-(2,4,6-trimethoxyphenyl)prop-2-en-1-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: (E)-3-(4-nitrophenyl)-1-(2,4,6-trimethoxyphenyl)prop-2-en-1-one
• 化学式: C₁₈H₁₇NO₆
• 分子量: 343.336
• InChiKey: VJNBRWWDKJRZIL-RMKNXTFCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  25
• 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：
  90.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (E)-3-(4-nitrophenyl)-1-(2,4,6-trimethoxyphenyl)prop-2-en-1-one 在 N-羟基-4-甲基苯磺酰胺 、 potassium carbonate 作用下， 以 甲醇 、 水 为溶剂， 反应 69.0h， 以75%的产率得到5-(4-nitrophenyl)-3-(2,4,6-trimethoxyphenyl)isoxazole
  参考文献：
  名称：

  3,5-二芳基异恶唑衍生物作为潜在抗癌药的设计，合成和生物学评估。

  摘要：

  本研究是在试图合成一类新的包括11种化合物（潜在的抗癌剂的情况下进行24 - 34共享3,5- diarylisoxazole作为芯）。通过IR，1 H NMR，13 C NMR和元素分析确定了新合成化合物的化学结构。通过使用癌症PC3细胞和非致瘤性PNT1a细胞评估了它们对前列腺癌的生物学潜力。有趣的是，化合物26与其他化合物的区别在于它具有相当高的选择性值，可与5-FU相比。装订方式26 通过基于GLIDE标准精度以及MM-GBSA计算的对接模拟，详细研究了针对核糖体蛋白S6激酶beta-1（S6K1）的核糖体蛋白。

  DOI：

  10.1016/j.bmcl.2020.127427
• 作为产物：
  描述：

  2-羟基-4,6-二甲氧基苯乙酮 在 potassium hydroxide 、 sodium hydroxide 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 48.0h， 生成 (E)-3-(4-nitrophenyl)-1-(2,4,6-trimethoxyphenyl)prop-2-en-1-one
  参考文献：
  名称：

  三甲氧基查尔酮衍生物抑制巴西利什曼原虫的生长：合成，生物学评估，分子建模和结构-活性关系（SAR）

  摘要：

  在这项工作中，我们描述了一系列查尔酮衍生物的合成，抗菌活性以及分子建模和结构-活性关系（SAR）评估。在这些化合物中，甲氧基查耳酮2h，2i，2j，2k和2l表现出显着的抗菌活性（IC 50  <10μM）。有趣的是2i（IC 50  = 2.7μM），2j（IC 50  =  3.9μM ）和2k（IC 50 = 4.6μM）衍生物表现出比对照药物喷他idine（IC 50 = 6.0μM）。我们的SAR研究表明，在苯环A上进行甲氧基二邻取代的重要性以及这些分子的前沿轨道HOMO系数分布与其活性之间的关系。活性最高的化合物2h，2i，2j，2k和2l符合Lipinski的5法则，这在理论上对于良好的药物吸收和通过生物膜的渗透非常重要。2j的电位分布（IC 50  = 3.9μM，CC 50  = 216μM）表明，这种查耳酮衍生物是一种命中化合物，需要在抗衰老药物设计中进一步探索。

  DOI：

  10.1016/j.bmc.2011.06.023

文献信息

• Synthesis and pharmacological activity of chalcones derived from 2,4,6-trimethoxyacetophenone in RAW 264.7 cells stimulated by LPS: Quantitative structure–activity relationships
  作者：Louise Domeneghini Chiaradia、Rodrigo dos Santos、Carlos Eduardo Vitor、André Alexandre Vieira、Paulo César Leal、Ricardo José Nunes、João Batista Calixto、Rosendo Augusto Yunes

  DOI：10.1016/j.bmc.2007.10.039

  日期：2008.1

  induced enzymes involved is potentially an important strategy for obtaining antiinflammatory agents. In the search for hits to obtain lead compounds for new drugs of this class, 14 synthetic chalcones derived from 2,4,6-trimethoxyacetophenone were evaluated in terms of their inhibitory action, in vitro, in relation to NO production in murine macrophages of the line RAW 264.7 induced by bacterial lipopolysaccharides

  通过改变所涉及的诱导酶的表达来抑制一氧化氮（NO）的产生可能是获得抗炎药的重要策略。为了寻找此类新药的先导化合物，在寻找成功的途径中，评估了14种衍生自2,4,6-三甲氧基苯乙酮的合成查耳酮在体外对小鼠巨噬细胞NO生成的抑制作用。细菌脂多糖（LPS）诱导的RAW 264.7品系。所有化合物都是在碱性条件下通过苯乙酮与相应的醛之间的醛缩合获得的。在四个独立的实验中，通过剂量与抑制作用曲线计算出的平均IC（50）值在1.34至27.60microM之间变化，并与阳性对照化合物1400W（IC（50）= 3）进行了比较。78microM），一种高度选择性的iNOS抑制剂（诱导型一氧化氮合酶）。八个查耳酮的平均IC（50）值小于或等于1400W的平均IC（50）值，这表明这些分子可能充当炎症过程的抑制剂。QSAR研究表明，B环中的吸电子基团似乎增加了亚硝酸盐生成的抑制，主要是在2位时。A环的邻位取代似乎是活性所必需的。
• [EN] NUCLEAR RECEPTOR MODULATORS AND THEIR USE FOR THE TREATMENT AND PREVENTION OF CANCER<br/>[FR] MODULATEURS DE RÉCEPTEURS NUCLÉAIRES ET LEUR UTILISATION POUR LE TRAITEMENT ET LA PRÉVENTION D'UN CANCER
  申请人：US HEALTH

  公开号：WO2012174436A1

  公开（公告）日：2012-12-20

  Disclosed are compounds which are nuclear receptor modulators that can act as antagonists to the androgen receptor, for example, a compound of Formula I: wherein R1 to R5 and X1 to X5 are as described herein, as well as pharmaceutically acceptable salts, solvates, and stereoisomers thereof. Pharmaceutical compositions comprising such compounds, as well as methods of use, and treatment for cancers, including prostate cancers, other nuclear receptor mediated cancers, and other conditions, are also disclosed.

  本文披露了一些化合物，它们是核受体调节剂，可以作为雄激素受体的拮抗剂，例如，公式I的化合物：其中R1至R5和X1至X5如本文所述，以及其药用盐、溶剂化合物和立体异构体。还披露了包括这些化合物的药物组合物，以及使用方法和治疗癌症，包括前列腺癌、其他核受体介导的癌症和其他疾病的方法。
• Mechanisms of action and structure-activity relationships of cytotoxic flavokawain derivatives
  作者：Charlotte Thieury、Nicolas Lebouvier、Rémy Le Guével、Yann Barguil、Gaëtan Herbette、Cyril Antheaume、Edouard Hnawia、Yoshinori Asakawa、Mohammed Nour、Thierry Guillaudeux

  DOI：10.1016/j.bmc.2017.01.049

  日期：2017.3

  22 Flavokawain derivatives (FKd) were obtained by one step syntheses in order to conduct a SAR study to understand the structural requirements for optimum and selective cytotoxicity. FKd and natural flavokawains A and B found into kava, a South Pacific traditional beverage, were evaluated against nine cancer and one healthy cell lines. The targeted cell cycle phases as well as the effects on the induction of apoptosis and cell cycle protein levels were investigated. Therapeutic improvements (more activity and selectivity) were achieved with FKd compared to natural flavokawains and notably with the 2',3,4',6'-tetramethoxychalcone (FKd 19). FKd induced a Gl/S arrest on p53 wild-type cells and an M arrest on p53 mutant-type, via the up-regulation of p21 and cyclin B1 proteins, followed by apoptosis. Moreover, FKd exhibited a 24 h-effect on Akt/mTor normal cells versus a 48 h-effect on Akt/mTor up-regulated cells. The SAR study resulted in the conclusion that trimethoxy A-ring allowed the best compromise between cytotoxicity and selectivity, as well as the substitution of the meta position on the B-ring and the use of halogens substituents. (C) 2017 Elsevier Ltd. All rights reserved.
• 2'-Substituted chalcone derivatives as inhibitors of interleukin-1 biosynthesis
  作者：Douglas G. Batt、Robin Goodman、David G. Jones、Janet S. Kerr、Lisa R. Mantegna、Candice McAllister、Robert C. Newton、Sherrill Nurnberg、Patricia K. Welch、Maryanne B. Covington

  DOI：10.1021/jm00062a016

  日期：1993.5

  A series of 2'-substituted chalcone derivatives has been found to show potent inhibition of the production of IL-1beta from human peripheral blood monocytes stimulated with lipopolysaccharide (LPS), with IC50 values in the 0.2-5.0-muM range. Some members of the series have also shown inhibition of septic shock induced in mice by injection of LPS, although with low potency. Qualitative structure-activity relationships have shown that the enone is required for activity, which may be mediated by conjugate addition of a biological nucleophile to the chalcone. Electron-poor aromatic rings beta to the ketone give enhanced potency. Although electronic effects in the other ring (directly attached to the ketone) are minimal, this ring must possess an ortho substituent for good activity without cytotoxicity, suggesting a degree of selectivity which would not be expected for simple, nonspecific alkylating agents.
• Synthesis of Xanthohumol Analogues and Discovery of Potent Thioredoxin Reductase Inhibitor as Potential Anticancer Agent
  作者：Baoxin Zhang、Dongzhu Duan、Chunpo Ge、Juan Yao、Yaping Liu、Xinming Li、Jianguo Fang

  DOI：10.1021/jm5016507

  日期：2015.2.26

  The selenoprotein thioredoxin reductases (TrxRs) are attractive targets for anticancer drugs development. Xanthohumol (Xn), a naturally occurring polyphenol chalcone from hops, has received increasing attention because of its multiple pharmacological activities. We synthesized Xn and its 43 analogues and discovered that compound 13n displayed the highest cytotoxicity toward HeLa cells (IC50 = 1.4 mu M). Structure-activity relationship study indicates that the prenyl group is not necessary for cytotoxicity, and introducing electron-withdrawing group, especially on the meta-position, is favored. In addition, methylation of the phenoxyl groups generally improves the potency. Mechanistic study revealed that 13n selectively inhibits TrxR and induces reactive oxygen species and apoptosis in HeLa cells. Cells overexpressing TrxR are resistant to 13n insult, while knockdown of TrxR sensitizes cells to 13n treatment, highlighting the physiological significance of targeting TrxR by 13n. The clarification of the structural determinants for the potency would guide the design of novel potent molecules for future development.