(E)-3-(4-fluorophenyl)-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-fluorophenyl)-1-(2,4,6-trimethoxyphenyl)prop-2-en-1-one
• 英文别名: 4-Fluoro-2',4',6'-trimethoxychalcone
• 化学式: C₁₈H₁₇FO₄
• 分子量: 316.329
• InChiKey: NERHFTSAOXRYQV-RMKNXTFCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 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：
  44.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (E)-3-(4-fluorophenyl)-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70%的产率得到5-(4-fluorophenyl)-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：

  对氟苯甲醛 、 2,4,6-三甲氧基苯乙酮 以 甲醇 为溶剂， 反应 15.0h， 生成 (E)-3-(4-fluorophenyl)-1-(2,4,6-trimethoxyphenyl)prop-2-en-1-one
  参考文献：
  名称：

  Trimethoxylated Halogenated Chalcones as Dual Inhibitors of MAO-B and BACE-1 for the Treatment of Neurodegenerative Disorders

  摘要：

  六种卤代三甲氧基查尔酮衍生物（CH1–CH6）被合成并进行了光谱表征。进一步评估这些化合物对单胺氧化酶（MAOs）和β-分泌酶（BACE-1）的抑制潜力。六种化合物对MAO-B的抑制作用比对MAO-A更有效，而在CH4–CH6中的2′,3′,4′-甲氧基对于MAO-B的抑制作用比CH1–CH3中的2′,4′,6′-甲氧基更有效。化合物CH5对MAO-B的抑制最为有效，IC50值为0.46 µM，其次是CH4（IC50 = 0.84 µM）。在2′,3′,4′-甲氧基衍生物（CH4-CH6）中，抑制顺序为B环对位的–Br在CH5 > –Cl在CH4 > –F在CH6。CH4和CH5对MAO-B具有选择性，其选择性指数（SI）值分别为15.1和31.3，超过MAO-A。CH4和CH5对BACE-1有中等抑制作用，IC50值分别为13.6和19.8 µM。在正常非洲绿猴肾细胞系（VERO）上使用MTT实验评估CH4和CH5的细胞活力研究时，发现两种化合物是安全的，只有在浓度超过200 µg/mL时才观察到轻微毒性作用。CH4和CH5降低了用H2O2处理的VERO细胞的活性氧（ROS）水平，表明两种化合物通过抗氧化活性对细胞具有保护作用。所有化合物通过平行人工膜渗透实验（PAMPA）显示出高血脑屏障透过性。主要化合物的分子对接和ADME预测提供了更多关于结合和中枢神经系统药物相似性背后的理解。从非试验性突变原性和心毒性研究结果来看，CH4和CH5是非突变原性的，且心脏毒性为非/弱。这些结果表明，CH4和CH5可能被考虑作为治疗神经功能障碍的候选药物。

  DOI：

  10.3390/pharmaceutics13060850

文献信息

• Enantioselective Ring Opening of<i>meso</i>-Epoxides with Silicon Tetrachloride Catalyzed by Pyridine<i>N</i>-Oxides Fused with the Bicyclo[3.3.1]nonane Framework
  作者：Algirdas Neniškis、Sigitas Stončius

  DOI：10.1002/ejoc.201500762

  日期：2015.10

  chiral Lewis basic organocatalysts that contain pyridine N-oxide moieties fused with the bicyclo[3.3.1]nonane framework is reported. The obtained pyridine N-oxides were employed as catalysts in the enantioselective ring opening of meso-epoxides with silicon tetrachloride. Derivative 1b endowed with two 2,4-diaryl-substituted pyridine N-oxide moieties proved to be a particularly effective catalyst for desymmetrization

  报道了新的手性路易斯碱性有机催化剂的合成，该催化剂含有与双环 [3.3.1] 壬烷骨架稠合的吡啶 N-氧化物部分。所得吡啶N-氧化物用作中间环氧化物与四氯化硅对映选择性开环的催化剂。具有两个 2,4-二芳基取代的吡啶 N-氧化物部分的衍生物 1b 被证明是一种特别有效的催化剂，可用于降冰片烯氧化物 16i 的去对称化，以提供前所未有的 96% ee 的 Wagner-Meerwein 重排产物 20i。双功能同源物 3 带有 4-芳基取代基，与脂环族环氧化物底物表现出中等至高水平的不对称诱导（47-88% ee）。
• Trimethoxylated Halogenated Chalcones as Dual Inhibitors of MAO-B and BACE-1 for the Treatment of Neurodegenerative Disorders
  作者：Vishal Payyalot Vishal、Jong Min Oh、Ahmed Khames、Mohamed A. Abdelgawad、Aathira Sujathan Nair、Lekshmi R. Nath、Nicola Gambacorta、Fulvio Ciriaco、Orazio Nicolotti、Hoon Kim、Bijo Mathew

  DOI：10.3390/pharmaceutics13060850

  日期：——

  Six halogenated trimethoxy chalcone derivatives (CH1–CH6) were synthesized and spectrally characterized. The compounds were further evaluated for their inhibitory potential against monoamine oxidases (MAOs) and β-secretase (BACE-1). Six compounds inhibited MAO-B more effectively than MAO-A, and the 2′,3′,4′-methoxy moiety in CH4–CH6 was more effective for MAO-B inhibition than the 2′,4′,6′-methoxy moiety in CH1–CH3. Compound CH5 most potently inhibited MAO-B, with an IC50 value of 0.46 µM, followed by CH4 (IC50 = 0.84 µM). In 2′,3′,4′-methoxy derivatives (CH4-CH6), the order of inhibition was –Br in CH5 > -Cl in CH4 > -F in CH6 at the para-position in ring B of chalcone. CH4 and CH5 were selective for MAO-B, with selectivity index (SI) values of 15.1 and 31.3, respectively, over MAO-A. CH4 and CH5 moderately inhibited BACE-1 with IC50 values of 13.6 and 19.8 µM, respectively. When CH4 and CH5 were assessed for their cell viability studies on the normal African Green Monkey kidney cell line (VERO) using MTT assays, it was noted that both compounds were found to be safe, and only a slightly toxic effect was observed in concentrations above 200 µg/mL. CH4 and CH5 decreased reactive oxygen species (ROS) levels of VERO cells treated with H2O2, indicating both compounds retained protective effects on the cells by antioxidant activities. All compounds showed high blood brain barrier permeabilities analyzed by a parallel artificial membrane permeability assay (PAMPA). Molecular docking and ADME prediction of the lead compounds provided more insights into the rationale behind the binding and the CNS drug likeness. From non-test mutagenicity and cardiotoxicity studies, CH4 and CH5 were non-mutagenic and non-/weak-cardiotoxic. These results suggest that CH4 and CH5 could be considered candidates for the cure of neurological dysfunctions.

  六种卤代三甲氧基查尔酮衍生物（CH1–CH6）被合成并进行了光谱表征。进一步评估这些化合物对单胺氧化酶（MAOs）和β-分泌酶（BACE-1）的抑制潜力。六种化合物对MAO-B的抑制作用比对MAO-A更有效，而在CH4–CH6中的2′,3′,4′-甲氧基对于MAO-B的抑制作用比CH1–CH3中的2′,4′,6′-甲氧基更有效。化合物CH5对MAO-B的抑制最为有效，IC50值为0.46 µM，其次是CH4（IC50 = 0.84 µM）。在2′,3′,4′-甲氧基衍生物（CH4-CH6）中，抑制顺序为B环对位的–Br在CH5 > –Cl在CH4 > –F在CH6。CH4和CH5对MAO-B具有选择性，其选择性指数（SI）值分别为15.1和31.3，超过MAO-A。CH4和CH5对BACE-1有中等抑制作用，IC50值分别为13.6和19.8 µM。在正常非洲绿猴肾细胞系（VERO）上使用MTT实验评估CH4和CH5的细胞活力研究时，发现两种化合物是安全的，只有在浓度超过200 µg/mL时才观察到轻微毒性作用。CH4和CH5降低了用H2O2处理的VERO细胞的活性氧（ROS）水平，表明两种化合物通过抗氧化活性对细胞具有保护作用。所有化合物通过平行人工膜渗透实验（PAMPA）显示出高血脑屏障透过性。主要化合物的分子对接和ADME预测提供了更多关于结合和中枢神经系统药物相似性背后的理解。从非试验性突变原性和心毒性研究结果来看，CH4和CH5是非突变原性的，且心脏毒性为非/弱。这些结果表明，CH4和CH5可能被考虑作为治疗神经功能障碍的候选药物。
• Design of potent fluoro-substituted chalcones as antimicrobial agents
  作者：Serdar Burmaoglu、Oztekin Algul、Arzu Gobek、Derya Aktas Anil、Mahmut Ulger、Busra Gul Erturk、Engin Kaplan、Aylin Dogen、Gönül Aslan

  DOI：10.1080/14756366.2016.1265517

  日期：2017.1.1

  resistance, we attempted to develop novel antitubercular and antimicrobial agents. For this purpose, we developed some new fluorine-substituted chalcone analogs (3, 4, 9-15, and 20-23) using a structure-activity relationship approach. Target compounds were evaluated for their antitubercular efficacy against Mycobacterium tuberculosis H37Rv and antimicrobial activity against five common pathogenic bacterial and

  由于细菌和真菌的耐药性不断提高，我们试图开发新型的抗结核和抗菌药物。为此，我们使用结构-活性关系方法开发了一些新的氟取代的查耳酮类似物（3、4、9-15和20-23）。评价目标化合物对结核分枝杆菌H37Rv的抗结核功效以及对5种常见病原细菌和3种常见真菌菌株的抗菌活性。三个衍生物（3、9和10）显示出显着的抗结核活性，IC50值≤16,760。与查尔酮结构的B环上具有单氟取代基的三甲氧基取代基支架衍生的化合物相比，相应的羟基类似物具有更好的抑制活性。就抗菌活性而言，
• 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.
• [EN] ESTROGEN RECEPTOR ALPHA COLIGANDS, AND METHODS OF USE THEREOF<br/>[FR] CO-LIGANDS DES RÉCEPTEURS DES OESTROGÈNES ALPHA ET LEURS PROCÉDÉS D'UTILISATION
  申请人：UNIV CALIFORNIA

  公开号：WO2017132135A1

  公开（公告）日：2017-08-03

  Provided herein is a coligand for the estrogen receptor (ER) α subunit, and methods of use thereof in treating conditions associated with ER signaling in an individual. The present ERα coligand may be a cell type-selective, allosteric modulator of ERα signaling. The ERα coligand, when administered to an individual, may modulate ER agonist-dependent signaling in a tissue-selective manner.